Details of Drug Off-Target (DOT)

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

• DOT Name: Potassium voltage-gated channel subfamily G member 3 (KCNG3)
• Synonyms: Voltage-gated potassium channel subunit Kv10.1; Voltage-gated potassium channel subunit Kv6.3
• Gene Name: KCNG3
• Related Disease:
  Squamous cell carcinoma
  Hirschsprung disease
• UniProt ID: KCNG3_HUMAN
• Pfam ID: PF02214 ; PF00520
• Sequence:
  MTFGRSGAASVVLNVGGARYSLSRELLKDFPLRRVSRLHGCRSERDVLEVCDDYDRERNE
  YFFDRHSEAFGFILLYVRGHGKLRFAPRMCELSFYNEMIYWGLEGAHLEYCCQRRLDDRM
  SDTYTFYSADEPGVLGRDEARPGGAEAAPSRRWLERMRRTFEEPTSSLAAQILASVSVVF
  VIVSMVVLCASTLPDWRNAAADNRSLDDRSRYSAGPGREPSGIIEAICIGWFTAECIVRF
  IVSKNKCEFVKRPLNIIDLLAITPYYISVLMTVFTGENSQLQRAGVTLRVLRMMRIFWVI
  KLARHFIGLQTLGLTLKRCYREMVMLLVFICVAMAIFSALSQLLEHGLDLETSNKDFTSI
  PAACWWVIISMTTVGYGDMYPITVPGRILGGVCVVSGIVLLALPITFIYHSFVQCYHELK
  FRSARYSRSLSTEFLN
• Function: Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; this promotes a reduction in the rate of activation and inactivation of the delayed rectifier voltage-gated potassium channel KCNB1.
• Tissue Specificity: Expressed in the brain, liver, testis, small intestine, colon, thymus and adrenal gland .
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[1]
Hirschsprung disease	DISUUSM1	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Potassium voltage-gated channel subfamily G member 3 (KCNG3).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Potassium voltage-gated channel subfamily G member 3 (KCNG3).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Potassium voltage-gated channel subfamily G member 3 (KCNG3).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Potassium voltage-gated channel subfamily G member 3 (KCNG3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Potassium voltage-gated channel subfamily G member 3 (KCNG3).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Potassium voltage-gated channel subfamily G member 3 (KCNG3).	[10]

2 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 voltage-gated channel subfamily G member 3 (KCNG3).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Potassium voltage-gated channel subfamily G member 3 (KCNG3).	[8]

References

• [1] DNA methylation biomarkers for lung cancer.Tumour Biol. 2012 Apr;33(2):287-96. doi: 10.1007/s13277-011-0282-2. Epub 2011 Dec 6.
• [2] Altered expression of KCNG3 and KCNG4 in Hirschsprung's disease.Pediatr Surg Int. 2019 Feb;35(2):193-197. doi: 10.1007/s00383-018-4394-2. Epub 2018 Nov 1.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.