KCNAB2

Chr 1

potassium voltage-gated channel subfamily A regulatory beta subunit 2

Also known as: AKR6A5, HKvbeta2, HKvbeta2.1, HKvbeta2.2, KCNA2B, KV-BETA-2

NCBI Gene: 8514ENSG00000069424UniProt: Q13303

KCNAB2 encodes a regulatory beta subunit of voltage-gated potassium channels that promotes channel inactivation and prevents neuronal hyperexcitability, with additional aldoketoreductase enzymatic activity. Mutations cause autosomal dominant epileptic encephalopathy with onset typically in infancy or early childhood. The gene is highly constrained against loss-of-function variants (pLI = 0.80, LOEUF = 0.385), indicating strong selective pressure for proper gene function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
56
P/LP submissions
0%
P/LP missense
0.39
LOEUF
DN
Mechanism· predicted
Clinical Summary— KCNAB2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 56 VUS of 172 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.800
Z-score 3.96
OE 0.18 (0.10–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.60Z-score
OE missense 0.55 (0.48–0.63)
145 obs / 263.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.18 (0.10–0.39)
0≤0.351.4
Missense OE0.55 (0.48–0.63)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 5 / 27.3Missense obs/exp: 145 / 263.6Syn Z: 0.44
DN
0.6648th %ile
GOF
0.4973th %ile
LOF
0.50top 25%

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

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic2
VUS56
Likely Benign35
Benign11
Conflicting1
54
Pathogenic
2
Likely Pathogenic
56
VUS
35
Likely Benign
11
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
2
0
2
VUS
0
47
9
0
56
Likely Benign
0
6
12
17
35
Benign
0
0
5
6
11
Conflicting
—1
Total0538223159

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

View in ClinVar →

Protein Context — Lollipop Plot

KCNAB2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients