KCNV2

potassium voltage-gated channel modifier subfamily V member 2, the group of Potassium voltage-gated channels

Basic information

Region (hg38): 9:2717510-2730037

Links

ENSG00000168263 ∙ NCBI:169522 ∙ OMIM:607604 ∙ HGNC:19698 ∙ Uniprot:Q8TDN2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cone dystrophy with supernormal rod response (Strong), mode of inheritance: AR
• cone dystrophy with supernormal rod response (Supportive), mode of inheritance: AR
• cone dystrophy with supernormal rod response (Definitive), mode of inheritance: AR
• inherited retinal dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinal cone dystrophy 3B	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	16909397

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KCNV2 gene.

• not provided (40 variants)
• Cone dystrophy with supernormal rod response (5 variants)
• Cone dystrophy (3 variants)
• cone dystrophy with supernormal rod electroretinogram (2 variants)
• Retinal dystrophy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KCNV2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	152	11	171
missense	4	6	355	16	5	386
nonsense	21	6	2			29
start loss		1				1
frameshift	16	4	3			23
inframe indel			15			15
splice donor/acceptor (+/-2bp)						0
splice region	1		3	3		7
non coding			15	13	6	34
Total	41	17	398	181	22

Highest pathogenic variant AF is 0.000118

Variants in KCNV2

This is a list of pathogenic ClinVar variants found in the KCNV2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-2717536-A-C		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 13, 2018)
9-2717560-G-A		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 13, 2018)
9-2717579-G-A		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 13, 2018)
9-2717595-T-C		Cone dystrophy with supernormal rod response	Likely benign (Jan 13, 2018)
9-2717629-C-T		Cone dystrophy with supernormal rod response	Likely benign (Jan 13, 2018)
9-2717646-A-T		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 13, 2018)
9-2717671-G-A		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 13, 2018)
9-2717676-T-G		Cone dystrophy with supernormal rod response	Benign (Apr 27, 2017)
9-2717698-C-G		Cone dystrophy with supernormal rod response	Benign (Jul 11, 2019)
9-2717704-C-T		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 12, 2018)
9-2717721-G-C		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 12, 2018)
9-2717725-C-T		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 12, 2018)
9-2717731-T-C		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 12, 2018)
9-2717734-G-A		Cone dystrophy with supernormal rod response	Uncertain significance (Jan 13, 2018)
9-2717738-C-T		KCNV2-related disorder	Likely benign (Feb 08, 2023)
9-2717740-A-G		Cone dystrophy with supernormal rod response	Likely pathogenic (Jan 14, 2019)
9-2717744-TCAAA-T		Cone dystrophy with supernormal rod response • Retinal dystrophy	Pathogenic (Feb 26, 2023)
9-2717749-C-G			Uncertain significance (Jun 07, 2022)
9-2717751-G-A			Likely benign (Feb 11, 2023)
9-2717754-T-C			Likely benign (Sep 23, 2022)
9-2717754-TGA-T		Retinal dystrophy	Pathogenic (Aug 26, 2022)
9-2717755-G-C		Cone dystrophy with supernormal rod response • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 28, 2022)
9-2717759-G-A			Uncertain significance (Aug 16, 2022)
9-2717759-G-C			Uncertain significance (Jul 05, 2022)
9-2717759-G-T		Cone dystrophy with supernormal rod response	Uncertain significance (Apr 28, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KCNV2	protein_coding	protein_coding	ENST00000382082	2	12536

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.19e-26	7.01e-7	125633	0	115	125748	0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-4.48	606	365	1.66	0.0000280	3503
Missense in Polyphen		216	133.17	1.622		1282
Synonymous	-5.24	253	167	1.52	0.0000145	1099
Loss of Function	-3.30	31	16.5	1.88	7.28e-7	175

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00135	0.00134
Ashkenazi Jewish	0.00	0.00
East Asian	0.000505	0.000489
Finnish	0.000198	0.000185
European (Non-Finnish)	0.000458	0.000440
Middle Eastern	0.000505	0.000489
South Asian	0.000404	0.000392
Other	0.000679	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potassium channel subunit. Modulates channel activity by shifting the threshold and the half-maximal activation to more negative values.
• Disease: DISEASE: Cone dystrophy retinal 3B (RCD3B) [MIM:610356]: A rare form of cone dystrophy associated with supernormal rod responses. The disorder is characterized by reduced visual acuity, photoaversion, night blindness, and abnormal color vision. At an early age, the retina shows subtle depigmentation at the macula and, later, more obvious areas of atrophy. {ECO:0000269|PubMed:16909397}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuronal System;Voltage gated Potassium channels;Potassium Channels (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.0969
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.45

Haploinsufficiency Scores

• pHI: 0.451
• hipred: N
• hipred_score: 0.251
• ghis: 0.408

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.630

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kcnv2
• Phenotype: skeleton phenotype; normal phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of ion transmembrane transport;protein homooligomerization;potassium ion transmembrane transport
• Cellular component: plasma membrane;voltage-gated potassium channel complex;integral component of membrane
• Molecular function: voltage-gated potassium channel activity