Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG14TPO)

• DOT Name: Glycosyltransferase 8 domain-containing protein 1 (GLT8D1)
• Synonyms: EC 2.4.1.-
• Gene Name: GLT8D1
• Related Disease:
  Cutaneous melanoma
  Melanoma
  Knee osteoarthritis
  Major depressive disorder
  Mental disorder
  Osteoarthritis
  Schizophrenia
  Bipolar disorder
  Amyotrophic lateral sclerosis
  Familial amyotrophic lateral sclerosis
• UniProt ID: GL8D1_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF01501
• Sequence:
  MSFRKVNIIILVLAVALFLLVLHHNFLSLSSLLRNEVTDSGIVGPQPIDFVPNALRHAVD
  GRQEEIPVVIAASEDRLGGAIAAINSIQHNTRSNVIFYIVTLNNTADHLRSWLNSDSLKS
  IRYKIVNFDPKLLEGKVKEDPDQGESMKPLTFARFYLPILVPSAKKAIYMDDDVIVQGDI
  LALYNTALKPGHAAAFSEDCDSASTKVVIRGAGNQYNYIGYLDYKKERIRKLSMKASTCS
  FNPGVFVANLTEWKRQNITNQLEKWMKLNVEEGLYSRTLAGSITTPPLLIVFYQQHSTID
  PMWNVRHLGSSAGKRYSPQFVKAAKLLHWNGHLKPWGRTASYTDVWEKWYIPDPTGKFNL
  IRRYTEISNIK

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cutaneous melanoma	DIS3MMH9	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[1]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[2]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[3]
Mental disorder	DIS3J5R8	Strong	Altered Expression	[3]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[4]
Schizophrenia	DISSRV2N	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[6]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[7]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Limited	Autosomal dominant	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[14]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[15]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[17]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Glycosyltransferase 8 domain-containing protein 1 (GLT8D1).	[21]

References

• [1] GLT8D1 overexpression as a novel prognostic biomarker in human cutaneous melanoma.Melanoma Res. 2019 Dec;29(6):612-620. doi: 10.1097/CMR.0000000000000631.
• [2] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [3] ITIH3 polymorphism may confer susceptibility to psychiatric disorders by altering the expression levels of GLT8D1.J Psychiatr Res. 2014 Mar;50:79-83. doi: 10.1016/j.jpsychires.2013.12.002. Epub 2013 Dec 15.
• [4] Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.Lancet. 2012 Sep 1;380(9844):815-23. doi: 10.1016/S0140-6736(12)60681-3. Epub 2012 Jul 3.
• [5] Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes.Nat Commun. 2018 Feb 26;9(1):838. doi: 10.1038/s41467-018-03247-3.
• [6] Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder.Mol Psychiatry. 2013 Feb;18(2):195-205. doi: 10.1038/mp.2011.157. Epub 2011 Dec 20.
• [7] Mutation analysis of GLT8D1 and ARPP21 genes in amyotrophic lateral sclerosis patients from mainland China.Neurobiol Aging. 2020 Jan;85:156.e1-156.e4. doi: 10.1016/j.neurobiolaging.2019.09.013. Epub 2019 Sep 25.
• [8] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] 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.
• [12] Gene expression changes associated with cytotoxicity identified using cDNA arrays. Funct Integr Genomics. 2000 Sep;1(2):114-26.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [21] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.