KCNV2

Chr 9AR

potassium voltage-gated channel modifier subfamily V member 2

Also known as: CDSRR, KV11.1, Kv8.2, RCD3B

NCBI Gene: 169522ENSG00000168263UniProt: Q8TDN2

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium voltage-gated channel subfamily V. This member is identified as a 'silent subunit', and it does not form homomultimers, but forms heteromultimers with several other subfamily members. Through obligatory heteromerization, it exerts a function-altering effect on other potassium channel subunits. This protein is strongly expressed in pancreas and has a weaker expression in several other tissues. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cone dystrophy with supernormal rod responsesMIM #610356
AR
1028
ClinVar variants
123
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KCNV2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
123 Pathogenic / Likely Pathogenic· 175 VUS of 1028 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.97LOEUF
pLI 0.000
Z-score -3.30
OE 1.88 (1.34–1.97)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-4.48Z-score
OE missense 1.66 (1.55–1.77)
606 obs / 365.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.88 (1.34–1.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.66 (1.55–1.77)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.52
0≤1.21.6
LoF obs/exp: 31 / 16.5Missense obs/exp: 606 / 365.3Syn Z: -5.24

ClinVar Variant Classifications

1028 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic102
Likely Pathogenic21
VUS175
Likely Benign171
Benign10
Conflicting17
102
Pathogenic
21
Likely Pathogenic
175
VUS
171
Likely Benign
10
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
92
0
102
Likely Pathogenic
2
7
12
0
21
VUS
1
139
30
5
175
Likely Benign
0
9
16
146
171
Benign
0
3
3
4
10
Conflicting
—17
Total11160153155496

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KCNV2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

KCNV2-related retinal cone dystrophy

definitive
ARLoss Of FunctionAbsent Gene Product, Uncertain
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cone dystrophy with supernormal rod responses

MIM #610356

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes.
Georgiou M et al.·Prog Retin Eye Res
2024Review
KCNV2 retinopathy: clinical features, molecular genetics and directions for future therapy.
Guimaraes TAC et al.·Ophthalmic Genet
2020Review
KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.
Georgiou M et al.·Am J Ophthalmol
2021
KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.
de Guimaraes TAC et al.·Br J Ophthalmol
2024
KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints-KCNV2 Study Group Report 2.
Georgiou M et al.·Am J Ophthalmol
2021
Cone dystrophy with supernormal rod responses: A rare KCNV2 gene variant.
Esteves-Leandro J et al.·Eur J Ophthalmol
2022
Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility.
Jorge BS et al.·Proc Natl Acad Sci U S A
2011
Pathognomonic (diagnostic) ERGs. A review and update.
Vincent A et al.·Retina
2013Review
Clinical vision and molecular loss: Integrating visual psychophysics with molecular genetics reveals key details of normal and abnormal visual processing.
Stockman A et al.·Prog Retin Eye Res
2021Review
Structural and functional characterization of an individual with the M285R KCNV2 hypomorphic allele.
de Guimaraes TAC et al.·Ophthalmic Genet
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools