Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2BFRNY)

DOT Name	Potassium channel subfamily K member 4 (KCNK4)
Synonyms	TWIK-related arachidonic acid-stimulated potassium channel protein; TRAAK; Two pore potassium channel KT4.1; Two pore K(+) channel KT4.1
Gene Name	KCNK4
Related Disease	Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome ( )
UniProt ID	KCNK4_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3UM7; 4I9W; 4RUE; 4RUF; 4WFE; 4WFF; 4WFG; 4WFH; 7LJ4; 7LJ5; 7LJA; 7LJB
Pfam ID	PF07885
Sequence	MRSTTLLALLALVLLYLVSGALVFRALEQPHEQQAQRELGEVREKFLRAHPCVSDQELGL LIKEVADALGGGADPETNSTSNSSHSAWDLGSAFFFSGTIITTIGYGNVALRTDAGRLFC IFYALVGIPLFGILLAGVGDRLGSSLRHGIGHIEAIFLKWHVPPELVRVLSAMLFLLIGC LLFVLTPTFVFCYMEDWSKLEAIYFVIVTLTTVGFGDYVAGADPRQDSPAYQPLVWFWIL LGLAYFASVLTTIGNWLRVVSRRTRAEMGGLTAQAASWTGTVTARVTQRAGPAAPPPEKE QPLLPPPPCPAQPLGRPRSPSPPEKAQPPSPPTASALDYPSENLAFIDESSDTQSERGCP LPRAPRGRRRPNPPRKPVRPRGPGRPRDKGVPV
Function	Voltage-insensitive potassium channel. Channel opening is triggered by mechanical forces that deform the membrane. Channel opening is triggered by raising the intracellular pH to basic levels. The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius. Plays a role in the perception of pain caused by heat. Plays a role in the sensory perception of pain caused by pressure.
Reactome Pathway	Phase 4 - resting membrane potential (R-HSA-5576886 ) TWIK related potassium channel (TREK) (R-HSA-1299503 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome	DISV80FH	Strong	Autosomal dominant	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Potassium channel subfamily K member 4 (KCNK4).	[2]
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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 decreases the methylation of Potassium channel subfamily K member 4 (KCNK4).	[3]
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References

1	Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome. Am J Hum Genet. 2018 Oct 4;103(4):621-630. doi: 10.1016/j.ajhg.2018.09.001.
2	The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
3	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.