Details of Drug Off-Target (DOT)

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

• DOT Name: Transmembrane protein 161B (TMEM161B)
• Gene Name: TMEM161B
• Related Disease:
  Alcohol dependence
  Acute myelogenous leukaemia
• UniProt ID: T161B_HUMAN
• Pfam ID: PF10268
• Sequence:
  MGVIGIQLVVTMVMASVMQKIIPHYSLARWLLCNGSLRWYQHPTEEELRILAGKQQKGKT
  KKDRKYNGHIESKPLTIPKDIDLHLETKSVTEVDTLALHYFPEYQWLVDFTVAATVVYLV
  TEVYYNFMKPTQEMNISLVWCLLVLSFAIKVLFSLTTHYFKVEDGGERSVCVTFGFFFFV
  KAMAVLIVTENYLEFGLETGFTNFSDSAMQFLEKQGLESQSPVSKLTFKFFLAIFCSFIG
  AFLTFPGLRLAQMHLDALNLATEKITQTLLHINFLAPLFMVLLWVKPITKDYIMNPPLGK
  ESIPLMTEATFDTLRLWLIILLCALRLAMMRSHLQAYLNLAQKCVDQMKKEAGRISTVEL
  QKMVARVFYYLCVIALQYVAPLVMLLHTTLLLKTLGNHSWGIYPESISTLPVDNSLLSNS
  VYSELPSAEGKMKVTVTQITVALSSLKNIFTPLLFRGLLSFLTWWIAACLFSTSLFGLFY
  HQYLTVA
• Function: Essential for maintaining normal cardiac rhythm in the developing heart and for neonatal survival. Inhibits potassium and calcium currents in the cardiomyocytes, this assists in timely action potential repolarization and thereby maintains normal cardiac rhythm.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alcohol dependence	DIS4ZSCO	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]

7 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 Transmembrane protein 161B (TMEM161B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane protein 161B (TMEM161B).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transmembrane protein 161B (TMEM161B).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane protein 161B (TMEM161B).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transmembrane protein 161B (TMEM161B).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transmembrane protein 161B (TMEM161B).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 161B (TMEM161B).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transmembrane protein 161B (TMEM161B).	[9]

References

• [1] The major depressive disorder GWAS-supported variant rs10514299 in TMEM161B-MEF2C predicts putamen activation during reward processing in alcohol dependence.Transl Psychiatry. 2018 Jul 13;8(1):131. doi: 10.1038/s41398-018-0184-9.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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] 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] 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.