Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNZHC9F)

• DOT Name: Transmembrane protein 186 (TMEM186)
• Gene Name: TMEM186
• Related Disease: GABA aminotransaminase deficiency
• UniProt ID: TM186_HUMAN
• Pfam ID: PF06979
• Sequence:
  MAALLRAVRRFRGKAVWERPLHGLWCCSGQEDPKRWVGSSSPISKEKLPNAETEKFWMFY
  RFDAIRTFGFLSRLKLAQTALTVVALPPGYYLYSQGLLTLNTVCLMSGISGFALTMLCWM
  SYFLRRLVGILYLNESGTMLRVAHLNFWGWRQDTYCPMADVIPLTETKDRPQEMFVRIQR
  YSGKQTFYVTLRYGRILDRERFTQVFGVHQMLK
• Function: As part of the MCIA complex, required for efficient assembly of the mitochondrial complex I.
• Reactome Pathway:
  Complex I biogenesis (R-HSA-6799198)
  Respiratory electron transport (R-HSA-611105)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
GABA aminotransaminase deficiency	DISB4GJ1	Strong	CausalMutation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 186 (TMEM186).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane protein 186 (TMEM186).	[3]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transmembrane protein 186 (TMEM186).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 186 (TMEM186).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 186 (TMEM186).	[6]

References

• [1] 2-Pyrrolidinone and Succinimide as Clinical Screening Biomarkers for GABA-Transaminase Deficiency: Anti-seizure Medications Impact Accurate Diagnosis.Front Neurosci. 2019 May 8;13:394. doi: 10.3389/fnins.2019.00394. eCollection 2019.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] 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.
• [5] 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.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.