Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT62F9KA)

• DOT Name: Membrane protein FAM174A (FAM174A)
• Synonyms: Hepatitis C virus NS5A-transactivated protein 6; HCV NS5A-transactivated protein 6; Transmembrane protein 157
• Gene Name: FAM174A
• UniProt ID: F174A_HUMAN
• Pfam ID: PF06679
• Sequence:
  MKASQCCCCLSHLLASVLLLLLLPELSGPLAVLLQAAEAAPGLGPPDPRPRTLPPLPPGP
  TPAQQPGRGLAEAAGPRGSEGGNGSNPVAGLETDDHGGKAGEGSVGGGLAVSPNPGDKPM
  TQRALTVLMVVSGAVLVYFVVRTVRMRRRNRKTRRYGVLDTNIENMELTPLEQDDEDDDN
  TLFDANHPRR

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Membrane protein FAM174A (FAM174A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Membrane protein FAM174A (FAM174A).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Membrane protein FAM174A (FAM174A).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Membrane protein FAM174A (FAM174A).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Membrane protein FAM174A (FAM174A).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Membrane protein FAM174A (FAM174A).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Membrane protein FAM174A (FAM174A).	[5]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Membrane protein FAM174A (FAM174A).	[8]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Membrane protein FAM174A (FAM174A).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Membrane protein FAM174A (FAM174A).	[7]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [9] Global changes in gene regulation demonstrate that unconjugated bilirubin is able to upregulate and activate select components of the endoplasmic reticulum stress response pathway. J Biochem Mol Toxicol. 2010 Mar-Apr;24(2):73-88.