Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT882DND)

• DOT Name: Protein FAM162A (FAM162A)
• Synonyms: E2-induced gene 5 protein; Growth and transformation-dependent protein; HGTD-P
• Gene Name: FAM162A
• Related Disease:
  Alcohol dependence
  Alcohol-induced disorders
  Alcohol-related disorders
• UniProt ID: F162A_HUMAN
• Pfam ID: PF06388
• Sequence:
  MGSLSGLRLAAGSCFRLCERDVSSSLRLTRSSDLKRINGFCTKPQESPGAPSRTYNRVPL
  HKPTDWQKKILIWSGRFKKEDEIPETVSLEMLDAAKNKMRVKISYLMIALTVVGCIFMVI
  EGKKAAQRHETLTSLNLEKKARLKEEAAMKAKTE
• Function: Proposed to be involved in regulation of apoptosis; the exact mechanism may differ between cell types/tissues. May be involved in hypoxia-induced cell death of transformed cells implicating cytochrome C release and caspase activation (such as CASP9) and inducing mitochondrial permeability transition. May be involved in hypoxia-induced cell death of neuronal cells probably by promoting release of AIFM1 from mitochondria to cytoplasm and its translocation to the nucleus; however, the involvement of caspases has been reported conflictingly.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	moderate	Genetic Variation	[1]
Alcohol-induced disorders	DIS3SFYT	moderate	Genetic Variation	[1]
Alcohol-related disorders	DIS3K4KK	moderate	Genetic Variation	[1]

24 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 Protein FAM162A (FAM162A).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM162A (FAM162A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FAM162A (FAM162A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein FAM162A (FAM162A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein FAM162A (FAM162A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein FAM162A (FAM162A).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein FAM162A (FAM162A).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein FAM162A (FAM162A).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein FAM162A (FAM162A).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Protein FAM162A (FAM162A).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein FAM162A (FAM162A).	[12]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Protein FAM162A (FAM162A).	[7]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Protein FAM162A (FAM162A).	[7]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Protein FAM162A (FAM162A).	[7]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Protein FAM162A (FAM162A).	[13]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Protein FAM162A (FAM162A).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein FAM162A (FAM162A).	[14]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Protein FAM162A (FAM162A).	[15]
AMEP	DMFELMQ	Phase 1	AMEP decreases the expression of Protein FAM162A (FAM162A).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein FAM162A (FAM162A).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein FAM162A (FAM162A).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein FAM162A (FAM162A).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein FAM162A (FAM162A).	[20]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Protein FAM162A (FAM162A).	[16]

References

• [1] Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.Am J Med Genet B Neuropsychiatr Genet. 2017 Dec;174(8):846-853. doi: 10.1002/ajmg.b.32604. Epub 2017 Oct 9.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] 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.
• [11] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [14] 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.
• [15] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [16] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [17] 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.
• [18] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [19] 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.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.