Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLS8OU5)

• DOT Name: Potassium voltage-gated channel subfamily V member 2 (KCNV2)
• Synonyms: Voltage-gated potassium channel subunit Kv8.2
• Gene Name: KCNV2
• Related Disease:
  Cone dystrophy with supernormal rod response
  Cone-rod dystrophy 2
  Inherited retinal dystrophy
  Cone dystrophy
  Epilepsy
  Retinopathy
  Disorder of orbital region
  Severe early-childhood-onset retinal dystrophy
• UniProt ID: KCNV2_HUMAN
• Pfam ID: PF02214 ; PF00520
• Sequence:
  MLKQSERRRSWSYRPWNTTENEGSQHRRSICSLGARSGSQASIHGWTEGNYNYYIEEDED
  GEEEDQWKDDLAEEDQQAGEVTTAKPEGPSDPPALLSTLNVNVGGHSYQLDYCELAGFPK
  TRLGRLATSTSRSRQLSLCDDYEEQTDEYFFDRDPAVFQLVYNFYLSGVLLVLDGLCPRR
  FLEELGYWGVRLKYTPRCCRICFEERRDELSERLKIQHELRAQAQVEEAEELFRDMRFYG
  PQRRRLWNLMEKPFSSVAAKAIGVASSTFVLVSVVALALNTVEEMQQHSGQGEGGPDLRP
  ILEHVEMLCMGFFTLEYLLRLASTPDLRRFARSALNLVDLVAILPLYLQLLLECFTGEGH
  QRGQTVGSVGKVGQVLRVMRLMRIFRILKLARHSTGLRAFGFTLRQCYQQVGCLLLFIAM
  GIFTFSAAVYSVEHDVPSTNFTTIPHSWWWAAVSISTVGYGDMYPETHLGRFFAFLCIAF
  GIILNGMPISILYNKFSDYYSKLKAYEYTTIRRERGEVNFMQRARKKIAECLLGSNPQLT
  PRQEN
• Function: Potassium channel subunit. Modulates channel activity by shifting the threshold and the half-maximal activation to more negative values.
• Tissue Specificity: Detected in lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, ovary and colon.
• Reactome Pathway: Voltage gated Potassium channels (R-HSA-1296072)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone dystrophy with supernormal rod response	DISHSXP5	Definitive	Autosomal recessive	[1]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Genetic Variation	[2]
Inherited retinal dystrophy	DISGGL77	Definitive	Autosomal recessive	[3]
Cone dystrophy	DIS7SAZZ	Strong	Genetic Variation	[4]
Epilepsy	DISBB28L	Strong	Biomarker	[5]
Retinopathy	DISB4B0F	Strong	Biomarker	[4]
Disorder of orbital region	DISH0ECJ	Limited	Biomarker	[6]
Severe early-childhood-onset retinal dystrophy	DISFDRFO	Limited	CausalMutation	[7]

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 voltage-gated channel subfamily V member 2 (KCNV2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Potassium voltage-gated channel subfamily V member 2 (KCNV2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Potassium voltage-gated channel subfamily V member 2 (KCNV2).	[9]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] Screening for variants in 20 genes in 130 unrelated patients with cone-rod dystrophy.Mol Med Rep. 2013 Jun;7(6):1779-85. doi: 10.3892/mmr.2013.1415. Epub 2013 Apr 5.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] The importance of electrophysiology in revealing a complete homozygous deletion of KCNV2.J AAPOS. 2013 Dec;17(6):641-3. doi: 10.1016/j.jaapos.2013.08.006. Epub 2013 Nov 7.
• [5] Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility.Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5443-8. doi: 10.1073/pnas.1017539108. Epub 2011 Mar 14.
• [6] Coexistence of KCNV2 associated cone dystrophy with supernormal rod electroretinogram and MFRP related oculopathy in a Turkish family.Br J Ophthalmol. 2013 Feb;97(2):169-73. doi: 10.1136/bjophthalmol-2012-302355. Epub 2012 Nov 10.
• [7] Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
• [8] 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.
• [9] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [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.