Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4VS9YY)

• DOT Name: Glycosyltransferase 8 domain-containing protein 2 (GLT8D2)
• Synonyms: EC 2.4.1.-
• Gene Name: GLT8D2
• Related Disease:
  Hepatitis C virus infection
  Liver cirrhosis
• UniProt ID: GL8D2_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF01501
• Sequence:
  MALLRKINQVLLFLLIVTLCVILYKKVHKGTVPKNDADDESETPEELEEEIPVVICAAAG
  RMGATMAAINSIYSNTDANILFYVVGLRNTLTRIRKWIEHSKLREINFKIVEFNPMVLKG
  KIRPDSSRPELLQPLNFVRFYLPLLIHQHEKVIYLDDDVIVQGDIQELYDTTLALGHAAA
  FSDDCDLPSAQDINRLVGLQNTYMGYLDYRKKAIKDLGISPSTCSFNPGVIVANMTEWKH
  QRITKQLEKWMQKNVEENLYSSSLGGGVATSPMLIVFHGKYSTINPLWHIRHLGWNPDAR
  YSEHFLQEAKLLHWNGRHKPWDFPSVHNDLWESWFVPDPAGIFKLNHHS

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[1]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[15]

2 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 Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Glycosyltransferase 8 domain-containing protein 2 (GLT8D2).	[14]

References

• [1] Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.Gastroenterology. 2012 Nov;143(5):1244-1252.e12. doi: 10.1053/j.gastro.2012.07.097. Epub 2012 Jul 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] 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.
• [12] 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.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] 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.