KCNAB3

Chr 17

potassium voltage-gated channel subfamily A regulatory beta subunit 3

Also known as: AKR6A9, KCNA3.1B, KCNA3B, KV-BETA-3

This gene encodes a beta subunit that regulates voltage-gated potassium channels, particularly by increasing inactivation of Kv1.5 channels and potentially mediating channel closure. Mutations cause early infantile epileptic encephalopathy, characterized by seizures beginning in infancy with severe developmental impairment. The condition follows an autosomal dominant inheritance pattern, and the gene shows extreme constraint against loss-of-function variants (pLI near 1.0).

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.20
Clinical SummaryKCNAB3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.20LOEUF
pLI 0.000
Z-score 0.67
OE 0.87 (0.651.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.01Z-score
OE missense 1.00 (0.901.11)
236 obs / 236.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.87 (0.651.20)
00.351.4
Missense OE1.00 (0.901.11)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 28 / 32.1Missense obs/exp: 236 / 236.2Syn Z: 0.29
DN
0.6550th %ile
GOF
0.6150th %ile
LOF
0.4431th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KCNAB3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC