Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRTZUF5)

• DOT Name: C1GALT1-specific chaperone 1 (C1GALT1C1)
• Synonyms: C38H2-like protein 1; C38H2-L1; Core 1 beta1,3-galactosyltransferase 2; C1Gal-T2; C1GalT2; Core 1 beta3-Gal-T2; Core 1 beta3-galactosyltransferase-specific molecular chaperone
• Gene Name: C1GALT1C1
• Related Disease:
  Colonic neoplasm
  Nephropathy
  Advanced cancer
  Autoimmune disease
  Capillary hemangioma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Hemangioma
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Matthew-Wood syndrome
  Neoplasm
  Pancreatic cancer
  Vitiligo
  Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature
• UniProt ID: C1GLC_HUMAN
• Sequence:
  MLSESSSFLKGVMLGSIFCALITMLGHIRIGHGNRMHHHEHHHLQAPNKEDILKISEDER
  MELSKSFRVYCIILVKPKDVSLWAAVKETWTKHCDKAEFFSSENVKVFESINMDTNDMWL
  MMRKAYKYAFDKYRDQYNWFFLARPTTFAIIENLKYFLLKKDPSQPFYLGHTIKSGDLEY
  VGMEGGIVLSVESMKRLNSLLNIPEKCPEQGGMIWKISEDKQLAVCLKYAGVFAENAEDA
  DGKDVFNTKSVGLSIKEAMTYHPNQVVEGCCSDMAVTFNGLTPNQMHVMMYGVYRLRAFG
  HIFNDALVFLPPNGSDND
• Function: Probable chaperone required for the generation of 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins. Probably acts as a specific molecular chaperone assisting the folding/stability of core 1 beta-3-galactosyltransferase (C1GALT1).
• Tissue Specificity: Ubiquitously expressed. Abundantly expressed in salivary gland, stomach, small intestine, kidney, and testis and at intermediate levels in whole brain, cerebellum, spinal cord, thymus, spleen, trachea, lung, pancreas, ovary, and uterus.
• KEGG Pathway:
  Mucin type O-glycan biosynthesis (hsa00512)
  Other types of O-glycan biosynthesis (hsa00514)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  O-linked glycosylation of mucins (R-HSA-913709)
  Defective C1GALT1C1 causes TNPS (R-HSA-5083632)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colonic neoplasm	DISSZ04P	Definitive	Altered Expression	[1]
Nephropathy	DISXWP4P	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[4]
Capillary hemangioma	DISQ8XPT	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[6]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[7]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[7]
Hemangioma	DISDCGAG	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[8]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[9]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Pancreatic cancer	DISJC981	Strong	Biomarker	[10]
Vitiligo	DISR05SL	Strong	Biomarker	[9]
Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature	DISUJXOY	Limited	X-linked	[11]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[19]
Menadione	DMSJDTY	Approved	Menadione affects the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[21]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[22]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of C1GALT1-specific chaperone 1 (C1GALT1C1).	[25]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of C1GALT1-specific chaperone 1 (C1GALT1C1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of C1GALT1-specific chaperone 1 (C1GALT1C1).	[24]

References

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• [3] Multiple cancer-specific antigens are targeted by a chimeric antigen receptor on a single cancer cell.JCI Insight. 2019 Nov 1;4(21):e130416. doi: 10.1172/jci.insight.130416.
• [4] No evidence for a role of cosmc-chaperone mutations in European IgA nephropathy patients.Nephrol Dial Transplant. 2009 Jan;24(1):321-4. doi: 10.1093/ndt/gfn538. Epub 2008 Oct 7.
• [5] COSMC is overexpressed in proliferating infantile hemangioma and enhances endothelial cell growth via VEGFR2.PLoS One. 2013;8(2):e56211. doi: 10.1371/journal.pone.0056211. Epub 2013 Feb 12.
• [6] Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29.Int J Clin Exp Pathol. 2015 Mar 1;8(3):2590-602. eCollection 2015.
• [7] The Role of Sialyl-Tn in Cancer.Int J Mol Sci. 2016 Feb 24;17(3):275. doi: 10.3390/ijms17030275.
• [8] C1GALT1C1/COSMC is a novel prognostic biomarker for hepatocellular carcinoma.Clin Res Hepatol Gastroenterol. 2020 Jun;44(3):310-320. doi: 10.1016/j.clinre.2019.07.017. Epub 2019 Aug 27.
• [9] Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases.PLoS One. 2014 Dec 5;9(12):e113684. doi: 10.1371/journal.pone.0113684. eCollection 2014.
• [10] COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer.Mol Cancer. 2015 May 29;14:109. doi: 10.1186/s12943-015-0386-1.
• [11] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [12] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [13] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [14] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [17] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [18] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [19] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [20] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [21] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [22] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [25] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.