Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFP82TK)

• DOT Name: Potassium channel subfamily K member 12 (KCNK12)
• Synonyms: Tandem pore domain halothane-inhibited potassium channel 2; THIK-2
• Gene Name: KCNK12
• Related Disease: Colorectal carcinoma
• UniProt ID: KCNKC_HUMAN
• Pfam ID: PF07885
• Sequence:
  MSSRSPRPPPRRSRRRLPRPSCCCCCCRRSHLNEDTGRFVLLAALIGLYLVAGATVFSAL
  ESPGEAEARARWGATLRNFSAAHGVAEPELRAFLRHYEAALAAGVRADALRPRWDFPGAF
  YFVGTVVSTIGFGMTTPATVGGKAFLIAYGLFGCAGTILFFNLFLERIISLLAFIMRACR
  ERQLRRSGLLPATFRRGSALSEADSLAGWKPSVYHVLLILGLFAVLLSCCASAMYTSVEG
  WDYVDSLYFCFVTFSTIGFGDLVSSQHAAYRNQGLYRLGNFLFILLGVCCIYSLFNVISI
  LIKQVLNWMLRKLSCRCCARCCPAPGAPLARRNAITPGSRLRRRLAALGADPAARDSDAE
  GRRLSGELISMRDLTASNKVSLALLQKQLSETANGYPRSVCVNTRQNGFSGGVGALGIMN
  NRLAETSASR
• Function: Probable potassium channel subunit. No channel activity observed in heterologous systems. May need to associate with another protein to form a functional channel.
• Reactome Pathway: Phase 4 - resting membrane potential (R-HSA-5576886)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Disputed	Posttranslational Modification	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Potassium channel subfamily K member 12 (KCNK12).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Potassium channel subfamily K member 12 (KCNK12).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Potassium channel subfamily K member 12 (KCNK12).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Potassium channel subfamily K member 12 (KCNK12).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Potassium channel subfamily K member 12 (KCNK12).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Potassium channel subfamily K member 12 (KCNK12).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Potassium channel subfamily K member 12 (KCNK12).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Potassium channel subfamily K member 12 (KCNK12).	[9]

References

• [1] Methyl-CpG binding column-based identification of nine genes hypermethylated in colorectal cancer.Mol Carcinog. 2011 Nov;50(11):846-56. doi: 10.1002/mc.20763. Epub 2011 Mar 22.
• [2] 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.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] 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.
• [8] Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
• [9] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.