Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRB3JK7)

• DOT Name: Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1)
• Synonyms: EC 2.4.1.-; Forssman glycolipid synthase-like protein
• Gene Name: GBGT1
• Related Disease:
  Advanced cancer
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Venous thromboembolism
• UniProt ID: GBGT1_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF03414
• Sequence:
  MHRRRLALGLGFCLLAGTSLSVLWVYLENWLPVSYVPYYLPCPEIFNMKLHYKREKPLQP
  VVWSQYPQPKLLEHRPTQLLTLTPWLAPIVSEGTFNPELLQHIYQPLNLTIGVTVFAVGK
  YTHFIQSFLESAEEFFMRGYRVHYYIFTDNPAAVPGVPLGPHRLLSSIPIQGHSHWEETS
  MRRMETISQHIAKRAHREVDYLFCLDVDMVFRNPWGPETLGDLVAAIHPSYYAVPRQQFP
  YERRRVSTAFVADSEGDFYYGGAVFGGQVARVYEFTRGCHMAILADKANGIMAAWREESH
  LNRHFISNKPSKVLSPEYLWDDRKPQPPSLKLIRFSTLDKDISCLRS
• Function: Has lost the ability to synthesize Forssman glycolipid antigen (FORS1/FG). Might have acquired an alternative function in glycosphingolipid metabolism, but it remains to be established. It appears to have drifted more slowly than confirmed pseudogenes in the glycosyltransferase 6 family, suggesting that it has remained under evolutionary pressure.
• Tissue Specificity: Widely expressed. Expressed at higher level in placenta, ovary and peripheral blood leukocyte, whereas it is weakly expressed in liver, thymus, and testis . Expressed in bone marrow erythroid cells .
• KEGG Pathway:
  Glycosphingolipid biosynthesis - globo and isoglobo series (hsa00603)
  Metabolic pathways (hsa01100)
• BioCyc Pathway: MetaCyc:ENSG00000148288-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Posttranslational Modification	[1]
Ovarian cancer	DISZJHAP	Definitive	Posttranslational Modification	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Posttranslational Modification	[1]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	[6]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	[8]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 (GBGT1).	[7]

References

• [1] Expression of GBGT1 is epigenetically regulated by DNA methylation in ovarian cancer cells.BMC Mol Biol. 2014 Oct 7;15:24. doi: 10.1186/1471-2199-15-24.
• [2] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [8] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [9] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.