KCNA6

Chr 12

potassium voltage-gated channel subfamily A member 6

Also known as: HBK2, KV1.6, PPP1R96

NCBI Gene: 3742ENSG00000151079UniProt: P17658

Potassium 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class. The coding region of this gene is intronless, and the gene is clustered with genes KCNA1 and KCNA5 on chromosome 12. [provided by RefSeq, Jul 2008]

0
ClinVar variants
0
Pathogenic / LP
0.50
pLI score
0
Active trials
Clinical Summary— KCNA6
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.53LOEUF
pLI 0.497
Z-score 2.84
OE 0.20 (0.09–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
3.05Z-score
OE missense 0.53 (0.47–0.60)
180 obs / 337.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.20 (0.09–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.47–0.60)
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.0.97
0≤1.21.6
LoF obs/exp: 3 / 14.8Missense obs/exp: 180 / 337.6Syn Z: 0.32

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KCNA6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo missense variants of KCNA3, KCNA4, and KCNA6 cause early onset developmental epileptic encephalopathy.
Tsai MH et al.·Hum Mol Genet
2025Case report
Membrane-wide screening identifies potential tissue-specific determinants of SARS-CoV-2 tropism.
Dinesh RK et al.·PLoS Pathog
2025
Generalized myokymia, or neuromyotonia, or both in dogs with or without spinocerebellar ataxia.
Vanhaesebrouck A et al.·J Vet Intern Med
2023
De novo KCNA6 variants with attenuated K(V) 1.6 channel deactivation in patients with epilepsy.
Salpietro V et al.·Epilepsia
2023Cohort
Antisense Oligonucleotide Therapy Targeted Against ATXN3 Improves Potassium Channel-Mediated Purkinje Neuron Dysfunction in Spinocerebellar Ataxia Type 3.
Bushart DD et al.·Cerebellum
2021
Inherited neuromyotonia: a clinical and genetic study of a family.
Falace A et al.·Neuromuscul Disord
2007Case report
A gene for episodic ataxia/myokymia maps to chromosome 12p13.
Litt M et al.·Am J Hum Genet
1994Case 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.

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External Resources

Links to major genomics databases and tools