KCNV2

Chr 9AR

potassium voltage-gated channel modifier subfamily V member 2

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

NCBI Gene: 169522 ENSG00000168263 UniProt: Q8TDN2 OMIM: 607604

This gene encodes a voltage-gated potassium channel subunit that modulates channel activity by shifting activation thresholds to more negative values and forms heteromultimers with other potassium channel subunits rather than functioning alone. Biallelic mutations cause cone dystrophy with supernormal rod responses, an autosomal recessive retinal disorder. The gene shows tolerance to loss-of-function variants (high LOEUF score), suggesting the pathogenic variants may have effects beyond simple protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.971 OMIM phenotype

Clinical Summary— KCNV2

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Gene-Disease Validity (ClinGen)

inherited retinal dystrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-4.48Z-score

OE missense 1.66 (1.55–1.77)

606 obs / 365.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.88 (1.34–1.97)

0≤0.351.4

Missense OE?1.66 (1.55–1.77)

0≤0.61.4

Synonymous OE?1.52

0≤1.21.6

LoF obs/exp: 31 / 16.5Missense obs/exp: 606 / 365.3Syn Z: -5.24

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveKCNV2-related retinal cone dystrophyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7326th %ile

GOF

0.83top 5%

LOF

0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.