KCNAB1

Chr 3

potassium voltage-gated channel subfamily A regulatory beta subunit 1

Also known as: AKR6A3, KCNA1B, KV-BETA-1, Kvb1.3, hKvBeta3, hKvb3

NCBI Gene: 7881 ENSG00000169282 UniProt: Q14722 OMIM: 601141

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 includes distinct isoforms which are encoded by alternatively spliced transcript variants of this gene. Some of these isoforms are beta subunits, which form heteromultimeric complexes with alpha subunits and modulate the activity of the pore-forming alpha subunits. [provided by RefSeq, Apr 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.51

Clinical Summary— KCNAB1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

24 VUS of 43 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.042

Z-score 3.56

OE 0.28 (0.16–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.15Z-score

OE missense 0.60 (0.53–0.69)

142 obs / 234.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.28 (0.16–0.51)

0≤0.351.4

Missense OE?0.60 (0.53–0.69)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 8 / 28.5Missense obs/exp: 142 / 234.8Syn Z: 0.59

This gene — mechanism propensity

0.77top 25%

GOF

0.6832th %ile

LOF

0.3164th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

43 submitted variants in ClinVar

ClinVar

Classification Summary

VUS24

Likely Benign1

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	24	0	24
Likely Benign	1	0	1
Benign	2	2	4
Total	27	2	29

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap KCNAB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →