Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX1JIEM)

• DOT Name: Transmembrane protein 185A (TMEM185A)
• Synonyms: Protein FAM11A
• Gene Name: TMEM185A
• Related Disease:
  X-linked intellectual disability
  Autism
  Autism spectrum disorder
  Pervasive developmental disorder
  Intellectual disability
• UniProt ID: T185A_HUMAN
• Pfam ID: PF10269
• Sequence:
  MNLRGLFQDFNPSKFLIYACLLLFSVLLALRLDGIIQWSYWAVFAPIWLWKLMVIVGASV
  GTGVWARNPQYRAEGETCVEFKAMLIAVGIHLLLLMFEVLVCDRIERGSHFWLLVFMPLF
  FVSPVSVAACVWGFRHDRSLELEILCSVNILQFIFIALRLDKIIHWPWLVVCVPLWILMS
  FLCLVVLYYIVWSVLFLRSMDVIAEQRRTHITMALSWMTIVVPLLTFEILLVHKLDGHNA
  FSCIPIFVPLWLSLITLMATTFGQKGGNHWWFGIRKDFCQFLLEIFPFLREYGNISYDLH
  HEDNEETEETPVPEPPKIAPMFRKKARVVITQSPGKYVLPPPKLNIEMPD

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
X-linked intellectual disability	DISYJBY3	Definitive	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[2]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[2]
Intellectual disability	DISMBNXP	Limited	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 Transmembrane protein 185A (TMEM185A).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transmembrane protein 185A (TMEM185A).	[9]

7 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 Transmembrane protein 185A (TMEM185A).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Transmembrane protein 185A (TMEM185A).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transmembrane protein 185A (TMEM185A).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane protein 185A (TMEM185A).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transmembrane protein 185A (TMEM185A).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 185A (TMEM185A).	[11]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Transmembrane protein 185A (TMEM185A).	[12]

References

• [1] A simple multiplex FRAXA, FRAXE, and FRAXF PCR assay convenient for wide screening programs.Hum Mutat. 1999;13(2):166-9. doi: 10.1002/(SICI)1098-1004(1999)13:2<166::AID-HUMU10>3.0.CO;2-X.
• [2] Lack of expansion of triplet repeats in the FMR1, FRAXE, and FRAXF loci in male multiplex families with autism and pervasive developmental disorders.Am J Med Genet. 1996 Aug 9;64(2):399-403. doi: 10.1002/(SICI)1096-8628(19960809)64:2<399::AID-AJMG33>3.0.CO;2-8.
• [3] Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island.Nat Genet. 1996 May;13(1):109-13. doi: 10.1038/ng0596-109.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] 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.