KCNAB3

Chr 17

potassium voltage-gated channel subfamily A regulatory beta subunit 3

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

NCBI Gene: 9196 ENSG00000170049 UniProt: O43448 OMIM: 604111

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).

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. The encoded protein is one of the beta subunits, which are auxiliary proteins associating with functional Kv-alpha subunits. The encoded protein forms a heterodimer with the potassium voltage-gated channel, shaker-related subfamily, member 5 gene product and regulates the activity of the alpha subunit. [provided by RefSeq, May 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.20

Clinical Summary— KCNAB3

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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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ClinVar Variants

68 VUS of 78 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.000

Z-score 0.67

OE 0.87 (0.65–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.90–1.11)

236 obs / 236.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.65–1.20)

0≤0.351.4

Missense OE?1.00 (0.90–1.11)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 28 / 32.1Missense obs/exp: 236 / 236.2Syn Z: 0.29

This gene — mechanism propensity

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

78 submitted variants in ClinVar

ClinVar

Classification Summary

VUS68

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	68	68
Likely Benign	0	0
Benign	0	0
Total	68	68

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap KCNAB3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →