Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG2NEZM)

DOT Name	Potassium channel subfamily K member 17 (KCNK17)
Synonyms	2P domain potassium channel Talk-2; Acid-sensitive potassium channel protein TASK-4; TWIK-related acid-sensitive K(+) channel 4; TWIK-related alkaline pH-activated K(+) channel 2; TALK-2
Gene Name	KCNK17
Related Disease	Arrhythmia ( ) Atrial fibrillation ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Hepatocellular carcinoma ( ) Liver cancer ( ) Neoplasm ( ) Transitional cell carcinoma ( ) Urothelial carcinoma ( ) Stroke ( ) Heart arrhythmia ( )
UniProt ID	KCNKH_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF07885
Sequence	MYRPRARAAPEGRVRGCAVPSTVLLLLAYLAYLALGTGVFWTLEGRAAQDSSRSFQRDKW ELLQNFTCLDRPALDSLIRDVVQAYKNGASLLSNTTSMGRWELVGSFFFSVSTITTIGYG NLSPNTMAARLFCIFFALVGIPLNLVVLNRLGHLMQQGVNHWASRLGGTWQDPDKARWLA GSGALLSGLLLFLLLPPLLFSHMEGWSYTEGFYFAFITLSTVGFGDYVIGMNPSQRYPLW YKNMVSLWILFGMAWLALIIKLILSQLETPGRVCSCCHHSSKEDFKSQSWRQGPDREPES HSPQQGCYPEGPMGIIQHLEPSAHAAGCGKDS
Function	Outward rectifying potassium channel. Produces rapidly activating and non-inactivating outward rectifier K(+) currents.
Reactome Pathway	Phase 4 - resting membrane potential (R-HSA-5576886 ) TWIK-related alkaline pH activated K+ channel (TALK) (R-HSA-1299361 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Arrhythmia	DISFF2NI	Strong	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Liver cancer	DISDE4BI	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[3]
Urothelial carcinoma	DISRTNTN	Strong	Biomarker	[3]
Stroke	DISX6UHX	moderate	Genetic Variation	[4]
Heart arrhythmia	DISLKUNL	Limited	Unknown	[5]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Potassium channel subfamily K member 17 (KCNK17).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Potassium channel subfamily K member 17 (KCNK17).	[7]
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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 increases the methylation of Potassium channel subfamily K member 17 (KCNK17).	[8]
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References

1	Identification and functional characterization of zebrafish K(2P)17.1 (TASK-4, TALK-2) two-pore-domain K(+) channels.Eur J Pharmacol. 2018 Jul 15;831:94-102. doi: 10.1016/j.ejphar.2018.05.007. Epub 2018 May 9.
2	KCNK levels are prognostic and diagnostic markers for hepatocellular carcinoma.Aging (Albany NY). 2019 Oct 2;11(19):8169-8182. doi: 10.18632/aging.102311. Epub 2019 Oct 2.
3	Comparison of genome-wide DNA methylation in urothelial carcinomas of patients with and without arsenic exposure.Environ Res. 2014 Jan;128:57-63. doi: 10.1016/j.envres.2013.10.006. Epub 2013 Nov 22.
4	Association of variants in KCNK17 gene with ischemic stroke and cerebral hemorrhage in a Chinese population.J Stroke Cerebrovasc Dis. 2014 Oct;23(9):2322-7. doi: 10.1016/j.jstrokecerebrovasdis.2014.04.029. Epub 2014 Aug 29.
5	The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
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	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
8	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.