Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMOT2KX)

• DOT Name: Potassium channel subfamily K member 13 (KCNK13)
• Synonyms: Tandem pore domain halothane-inhibited potassium channel 1; THIK-1
• Gene Name: KCNK13
• Related Disease:
  Atrial fibrillation
  Cardiac failure
  Congestive heart failure
  Neuralgia
  Alcohol dependence
• UniProt ID: KCNKD_HUMAN
• Pfam ID: PF07885
• Sequence:
  MAGRGFSWGPGHLNEDNARFLLLAALIVLYLLGGAAVFSALELAHERQAKQRWEERLANF
  SRGHNLSRDELRGFLRHYEEATRAGIRVDNVRPRWDFTGAFYFVGTVVSTIGFGMTTPAT
  VGGKIFLIFYGLVGCSSTILFFNLFLERLITIIAYIMKSCHQRQLRRRGALPQESLKDAG
  QCEVDSLAGWKPSVYYVMLILCTASILISCCASAMYTPIEGWSYFDSLYFCFVAFSTIGF
  GDLVSSQNAHYESQGLYRFANFVFILMGVCCIYSLFNVISILIKQSLNWILRKMDSGCCP
  QCQRGLLRSRRNVVMPGSVRNRCNISIETDGVAESDTDGRRLSGEMISMKDLLAANKASL
  AILQKQLSEMANGCPHQTSTLARDNEFSGGVGAFAIMNNRLAETSGDR
• Function: Potassium channel displaying weak inward rectification in symmetrical K(+) solution.
• Reactome Pathway:
  Phase 4 - resting membrane potential (R-HSA-5576886)
  Tandem pore domain halothane-inhibited K+ channel (THIK) (R-HSA-1299287)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[1]
Cardiac failure	DISDC067	Strong	Altered Expression	[1]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[1]
Neuralgia	DISWO58J	Strong	Biomarker	[2]
Alcohol dependence	DIS4ZSCO	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Potassium channel subfamily K member 13 (KCNK13).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Potassium channel subfamily K member 13 (KCNK13).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Potassium channel subfamily K member 13 (KCNK13).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Potassium channel subfamily K member 13 (KCNK13).	[7]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Potassium channel subfamily K member 13 (KCNK13).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Potassium channel subfamily K member 13 (KCNK13).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Potassium channel subfamily K member 13 (KCNK13).	[11]

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 13 (KCNK13).	[10]

References

• [1] Cardiac K(2P)13.1 (THIK-1) two-pore-domain K(+) channels: Pharmacological regulation and remodeling in atrial fibrillation.Prog Biophys Mol Biol. 2019 Jul;144:128-138. doi: 10.1016/j.pbiomolbio.2018.06.009. Epub 2018 Jul 6.
• [2] Amygdaloid administration of tetrapentylammonium attenuates development of pain and anxiety-like behavior following peripheral nerve injury.Pharmacol Rep. 2019 Feb;71(1):54-60. doi: 10.1016/j.pharep.2018.08.005. Epub 2018 Aug 17.
• [3] Ethanol acts on KCNK13 potassium channels in the ventral tegmental area to increase firing rate and modulate binge-like drinking.Neuropharmacology. 2019 Jan;144:29-36. doi: 10.1016/j.neuropharm.2018.10.008. Epub 2018 Oct 14.
• [4] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] 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.