Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT317PEL)

• DOT Name: Voltage-dependent calcium channel gamma-like subunit (TMEM37)
• Synonyms: Neuronal voltage-gated calcium channel gamma-like subunit; Transmembrane protein 37
• Gene Name: TMEM37
• Related Disease:
  Carcinoma
  Undifferentiated carcinoma
  Colon cancer
  Colon carcinoma
  Pancreatic cancer
• UniProt ID: CCGL_HUMAN
• Pfam ID: PF15108
• Sequence:
  MTAVGVQAQRPLGQRQPRRSFFESFIRTLIITCVALAVVLSSVSICDGHWLLAEDRLFGL
  WHFCTTTNQTICFRDLGQAHVPGLAVGMGLVRSVGALAVVAAIFGLEFLMVSQLCEDKHS
  QCKWVMGSILLLVSFVLSSGGLLGFVILLRNQVTLIGFTLMFWCEFTASFLLFLNAISGL
  HINSITHPWE
• Function: Thought to stabilize the calcium channel in an inactivated (closed) state. Modulates calcium current when coexpressed with CACNA1G.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Undifferentiated carcinoma	DISIAZST	Definitive	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Pancreatic cancer	DISJC981	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[18]

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 Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[9]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[19]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Voltage-dependent calcium channel gamma-like subunit (TMEM37).	[20]

References

• [1] Methylation silencing of angiopoietin-like 4 in rat and human mammary carcinomas.Cancer Sci. 2011 Jul;102(7):1337-43. doi: 10.1111/j.1349-7006.2011.01955.x. Epub 2011 May 12.
• [2] Independent prognostic genes and mechanism investigation for colon cancer.Biol Res. 2018 Apr 13;51(1):10. doi: 10.1186/s40659-018-0158-7.
• [3] Low P4HA2 and high PRTN3 expression predicts poor survival in patients with pancreatic cancer.Scand J Gastroenterol. 2019 Feb;54(2):246-251. doi: 10.1080/00365521.2019.1574360. Epub 2019 Mar 17.
• [4] 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.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [12] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [13] 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.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [19] 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.
• [20] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.