Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVDIS2V)

• DOT Name: Transmembrane protein 182 (TMEM182)
• Gene Name: TMEM182
• Related Disease:
  Psychotic disorder
  Squamous cell carcinoma
• UniProt ID: TM182_HUMAN
• Pfam ID: PF13903
• Sequence:
  MRLNIAIFFGALFGALGVLLFLVAFGSDYWLLATEVGRCSGEKNIENVTFHHEGFFWRCW
  FNGIVEENDSNIWKFWYTNQPPSKNCTHAYLSPYPFMRGEHNSTSYDSAVIYRGFWAVLM
  LLGVVAVVIASFLIICAAPFASHFLYKAGGGSYIAAGILFSLVVMLYVIWVQAVADMESY
  RNMKMKDCLDFTPSVLYGWSFFLAPAGIFFSLLAGLLFLVVGWHIQIHH
• Function: Negatively regulates myogenesis and skeletal muscle regeneration via its association with ITGB1. Modulates ITGB1 activation by decreasing ITGB1-LAMB1 interaction and inhibiting ITGB1-mediated intracellular signaling during myogenesis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psychotic disorder	DIS4UQOT	Strong	Genetic Variation	[1]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Transmembrane protein 182 (TMEM182).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 182 (TMEM182).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 182 (TMEM182).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transmembrane protein 182 (TMEM182).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transmembrane protein 182 (TMEM182).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Transmembrane protein 182 (TMEM182).	[7]

References

• [1] Genome-wide association study of atypical psychosis.Am J Med Genet B Neuropsychiatr Genet. 2013 Oct;162B(7):679-86. doi: 10.1002/ajmg.b.32164.
• [2] TNF--induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility.PLoS One. 2019 Mar 20;14(3):e0213463. doi: 10.1371/journal.pone.0213463. eCollection 2019.
• [3] 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.
• [4] 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.
• [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] 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.
• [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] 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.