Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ52G7V)

• DOT Name: Potassium voltage-gated channel subfamily H member 6 (KCNH6)
• Synonyms: Ether-a-go-go-related gene potassium channel 2; ERG-2; Eag-related protein 2; Ether-a-go-go-related protein 2; hERG-2; hERG2; Voltage-gated potassium channel subunit Kv11.2
• Gene Name: KCNH6
• Related Disease:
  Hyperglycemia
  Hyperinsulinemia
  Hypoglycemia
  Type-1/2 diabetes
  Adenoma
  Osteoporosis
  Psychotic disorder
  Schizophrenia
  Meningioma
  Endometrium adenocarcinoma
• UniProt ID: KCNH6_HUMAN
• Pfam ID: PF00027 ; PF00520 ; PF13426
• Sequence:
  MPVRRGHVAPQNTYLDTIIRKFEGQSRKFLIANAQMENCAIIYCNDGFCELFGYSRVEVM
  QQPCTCDFLTGPNTPSSAVSRLAQALLGAEECKVDILYYRKDASSFRCLVDVVPVKNEDG
  AVIMFILNFEDLAQLLAKCSSRSLSQRLLSQSFLGSEGSHGRPGGPGPGTGRGKYRTISQ
  IPQFTLNFVEFNLEKHRSSSTTEIEIIAPHKVVERTQNVTEKVTQVLSLGADVLPEYKLQ
  APRIHRWTILHYSPFKAVWDWLILLLVIYTAVFTPYSAAFLLSDQDESRRGACSYTCSPL
  TVVDLIVDIMFVVDIVINFRTTYVNTNDEVVSHPRRIAVHYFKGWFLIDMVAAIPFDLLI
  FRTGSDETTTLIGLLKTARLLRLVRVARKLDRYSEYGAAVLFLLMCTFALIAHWLACIWY
  AIGNVERPYLEHKIGWLDSLGVQLGKRYNGSDPASGPSVQDKYVTALYFTFSSLTSVGFG
  NVSPNTNSEKVFSICVMLIGSLMYASIFGNVSAIIQRLYSGTARYHTQMLRVKEFIRFHQ
  IPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGFPECLQADICLHLHRALLQHCPAFSGAGK
  GCLRALAVKFKTTHAPPGDTLVHLGDVLSTLYFISRGSIEILRDDVVVAILGKNDIFGEP
  VSLHAQPGKSSADVRALTYCDLHKIQRADLLEVLDMYPAFAESFWSKLEVTFNLRDAAGG
  LHSSPRQAPGSQDHQGFFLSDNQSGSPHELGPQFPSKGYSLLGPGSQNSMGAGPCAPGHP
  DAAPPLSISDASGLWPELLQEMPPRHSPQSPQEDPDCWPLKLGSRLEQLQAQMNRLESRV
  SSDLSRILQLLQKPMPQGHASYILEAPASNDLALVPIASETTSPGPRLPQGFLPPAQTPS
  YGDLDDCSPKHRNSSPRMPHLAVATDKTLAPSSEQEQPEGLWPPLASPLHPLEVQGLICG
  PCFSSLPEHLGSVPKQLDFQRHGSDPGFAGSWGH
• Function: Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current. Channel properties may be modulated by cAMP and subunit assembly.
• Tissue Specificity: Expressed in prolactin-secreting adenomas.
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperglycemia	DIS0BZB5	Definitive	Genetic Variation	[1]
Hyperinsulinemia	DISIDWT6	Definitive	Genetic Variation	[1]
Hypoglycemia	DISRCKR7	Definitive	Genetic Variation	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Genetic Variation	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Osteoporosis	DISF2JE0	Strong	Biomarker	[3]
Psychotic disorder	DIS4UQOT	Strong	Biomarker	[4]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Meningioma	DISPT4TG	moderate	Biomarker	[5]
Endometrium adenocarcinoma	DISY6744	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Potassium voltage-gated channel subfamily H member 6 (KCNH6).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Potassium voltage-gated channel subfamily H member 6 (KCNH6).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Potassium voltage-gated channel subfamily H member 6 (KCNH6).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Potassium voltage-gated channel subfamily H member 6 (KCNH6).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Potassium voltage-gated channel subfamily H member 6 (KCNH6).	[10]

References

• [1] From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion.Cell Rep. 2018 Dec 26;25(13):3800-3810.e6. doi: 10.1016/j.celrep.2018.12.005.
• [2] HERG K(+) currents in human prolactin-secreting adenoma cells.Pflugers Arch. 2003 Feb;445(5):589-600. doi: 10.1007/s00424-002-0980-0. Epub 2002 Dec 6.
• [3] Significant pathways detection in osteoporosis based on the bibliometric network.Eur Rev Med Pharmacol Sci. 2013 Jan;17(1):1-7.
• [4] Two four-marker haplotypes on 7q36.1 region indicate that the potassium channel gene HERG1 (KCNH2, Kv11.1) is related to schizophrenia: a case control study.Behav Brain Funct. 2010 May 28;6:27. doi: 10.1186/1744-9081-6-27.
• [5] MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma.Biochem Biophys Res Commun. 2015 May 1;460(2):354-61. doi: 10.1016/j.bbrc.2015.03.038. Epub 2015 Mar 14.
• [6] Selective expression of HERG and Kv2 channels influences proliferation of uterine cancer cells.Int J Oncol. 2004 Jul;25(1):153-9.
• [7] 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.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.