CACNA1B

Chr 9AR

calcium voltage-gated channel subunit alpha1 B

Also known as: BIII, CACNL1A5, CACNN, Cav2.2, DYT23, NEDNEH

The CACNA1B protein forms the alpha-1B subunit of N-type voltage-gated calcium channels, which mediate calcium entry into excitable cells and control neurotransmitter release at synapses, pain signaling, and neuronal migration. Autosomal recessive mutations cause a neurodevelopmental disorder characterized by seizures and nonepileptic hyperkinetic movements. The protein is highly intolerant to loss-of-function mutations, suggesting pathogenicity occurs through severe disruption of calcium channel function.

OMIMResearchSummary from OMIM, UniProt
LOFmechanismARLOEUF 0.241 OMIM phenotype
Clinical SummaryCACNA1B
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder with motor features · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 7.85
OE 0.16 (0.110.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
4.52Z-score
OE missense 0.65 (0.610.69)
841 obs / 1299.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.16 (0.110.24)
00.351.4
Missense OE0.65 (0.610.69)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 16 / 101.2Missense obs/exp: 841 / 1299.1Syn Z: -0.42
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCACNA1B-related neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movementsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5967th %ile
GOF
0.74top 25%
LOF
0.56top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CACNA1B · 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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