Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGT3E98)

• DOT Name: GRAM domain-containing protein 2B (GRAMD2B)
• Synonyms: HCV NS3-transactivated protein 2
• Gene Name: GRAMD2B
• Related Disease:
  Chronic renal failure
  End-stage renal disease
  Non-insulin dependent diabetes
• UniProt ID: GRM2B_HUMAN
• Pfam ID: PF02893
• Sequence:
  MTELQQDVEDTKPAKVLGKRESKLGSAHSEAENGVEEKKKACRSPTAQSPTPSVEADSPD
  QKKIISLWSKSSFDGASLASDKNDCKTESKNDPKTERKKSSSSSQYKANMHFHKLFLSVP
  TEEPLKQSFTCALQKEILYQGKLFVSENWICFHSKVFGKDTKISIPAFSVTLIKKTKTAL
  LVPNALIIATVTDRYIFVSLLSRDSTYKLLKSVCGHLENTSVGNSPNPSSAENSFRADRP
  SSLPLDFNDEFSDLDGVVQQRRQDMEGYSSSGSQTPESENSRDFHATESQTVLNVSKGEA
  KPTRADAHVNRVPEGKAKSLPVQGLSETVGILHKVKSQKCPMLHHILIFYAIVVCALIIS
  TFYMRYRINTLEEQLGLLTSIVDTHNTEQAAPSGLRSQVQFNVEVLCQELTANIVKLEKI
  QNNLQKLLENGD

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Limited	Genetic Variation	[1]
End-stage renal disease	DISXA7GG	Limited	Genetic Variation	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of GRAM domain-containing protein 2B (GRAMD2B).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of GRAM domain-containing protein 2B (GRAMD2B).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of GRAM domain-containing protein 2B (GRAMD2B).	[13]

16 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 GRAM domain-containing protein 2B (GRAMD2B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[17]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of GRAM domain-containing protein 2B (GRAMD2B).	[18]

References

• [1] Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans.Hum Genomics. 2019 May 15;13(1):21. doi: 10.1186/s40246-019-0205-7.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [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] Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4578-83.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [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.
• [16] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] 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.