Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPBO355)

• DOT Name: Protein FAM50A (FAM50A)
• Synonyms: Protein HXC-26; Protein XAP-5
• Gene Name: FAM50A
• Related Disease: Armfield syndrome
• UniProt ID: FA50A_HUMAN
• PDB ID: 8C6J
• Pfam ID: PF04921
• Sequence:
  MAQYKGAASEAGRAMHLMKKREKQREQMEQMKQRIAEENIMKSNIDKKFSAHYDAVEAEL
  KSSTVGLVTLNDMKAKQEALVKEREKQLAKKEQSKELQMKLEKLREKERKKEAKRKISSL
  SFTLEEEEEGGEEEEEAAMYEEEMEREEITTKKRKLGKNPDVDTSFLPDRDREEEENRLR
  EELRQEWEAKQEKIKSEEIEITFSYWDGSGHRRTVKMRKGNTMQQFLQKALEILRKDFSE
  LRSAGVEQLMYIKEDLIIPHHHSFYDFIVTKARGKSGPLFNFDVHDDVRLLSDATVEKDE
  SHAGKVVLRSWYEKNKHIFPASRWEPYDPEKKWDKYTIR
• Function: Probably involved in the regulation of pre-mRNA splicing.
• Tissue Specificity: Widely expressed in fetal and adult tissues. Mostly abundant in fetal brain, liver and kidney; in the adult, high levels were also observed in heart, skeletal muscle, spleen, thymus, prostate and small intestine. Expressed in fetal cerebellum and hypothalamus. Low expression is observed in fetal temporal lobe .
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Armfield syndrome	DISEMDUR	Moderate	X-linked	[1]

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 Protein FAM50A (FAM50A).	[2]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein FAM50A (FAM50A).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein FAM50A (FAM50A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FAM50A (FAM50A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein FAM50A (FAM50A).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein FAM50A (FAM50A).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein FAM50A (FAM50A).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein FAM50A (FAM50A).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein FAM50A (FAM50A).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein FAM50A (FAM50A).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein FAM50A (FAM50A).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein FAM50A (FAM50A).	[12]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Protein FAM50A (FAM50A).	[13]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] 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.
• [7] 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.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] 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.
• [10] 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.
• [11] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.