Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8ELIFL)

• DOT Name: Potassium channel subfamily K member 15 (KCNK15)
• Synonyms: Acid-sensitive potassium channel protein TASK-5; TWIK-related acid-sensitive K(+) channel 5; Two pore potassium channel KT3.3; Two pore K(+) channel KT3.3
• Gene Name: KCNK15
• Related Disease:
  Hepatocellular carcinoma
  Lung adenocarcinoma
• UniProt ID: KCNKF_HUMAN
• Pfam ID: PF07885
• Sequence:
  MRRPSVRAAGLVLCTLCYLLVGAAVFDALESEAESGRQRLLVQKRGALRRKFGFSAEDYR
  ELERLALQAEPHRAGRQWKFPGSFYFAITVITTIEYGHAAPGTDSGKVFCMFYALLGIPL
  TLVTFQSLGERLNAVVRRLLLAAKCCLGLRWTCVSTENLVVAGLLACAATLALGAVAFSH
  FEGWTFFHAYYYCFITLTTIGFGDFVALQSGEALQRKLPYVAFSFLYILLGLTVIGAFLN
  LVVLRFLVASADWPERAARTPSPRPPGAPESRGLWLPRRPARSVGSASVFCHVHKLERCA
  RDNLGFSPPSSPGVVRGGQAPRLGARWKSI
• Function: Probable potassium channel subunit. No channel activity observed in heterologous systems. May need to associate with another protein to form a functional channel.
• Tissue Specificity: Detected in pancreas, heart, placenta, lung, liver, kidney, ovary, testis, skeletal muscle and adrenal gland, and at lower levels in prostate, spleen and thyroid gland.
• Reactome Pathway: Phase 4 - resting membrane potential (R-HSA-5576886)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Potassium channel subfamily K member 15 (KCNK15).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Potassium channel subfamily K member 15 (KCNK15).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Potassium channel subfamily K member 15 (KCNK15).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Potassium channel subfamily K member 15 (KCNK15).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Potassium channel subfamily K member 15 (KCNK15).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Potassium channel subfamily K member 15 (KCNK15).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Potassium channel subfamily K member 15 (KCNK15).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Potassium channel subfamily K member 15 (KCNK15).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Potassium channel subfamily K member 15 (KCNK15).	[10]

References

• [1] 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.
• [2] Up-regulation of long non-coding RNA SPRY4-IT1 promotes tumor cell migration and invasion in lung adenocarcinoma.Oncotarget. 2017 Apr 7;8(31):51058-51065. doi: 10.18632/oncotarget.16918. eCollection 2017 Aug 1.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [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.
• [9] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.