CACNA1B

Chr 9AR

calcium voltage-gated channel subunit alpha1 B

NCBI Gene: 774ENSG00000148408UniProt: Q00975

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling (PubMed:25296916). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. Mediates Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity)

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movementsMIM #618497
AR
480
ClinVar variants
26
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CACNA1B
🧬
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.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 155 VUS of 480 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.24LOEUF
pLI 1.000
Z-score 7.85
OE 0.16 (0.11–0.24)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.52Z-score
OE missense 0.65 (0.61–0.69)
841 obs / 1299.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.16 (0.11–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.61–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 16 / 101.2Missense obs/exp: 841 / 1299.1Syn Z: -0.42

ClinVar Variant Classifications

480 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic7
VUS155
Likely Benign246
Benign53
19
Pathogenic
7
Likely Pathogenic
155
VUS
246
Likely Benign
53
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
10
0
19
Likely Pathogenic
7
0
0
0
7
VUS
0
148
7
0
155
Likely Benign
1
8
132
105
246
Benign
0
0
48
5
53
Total17156197110480

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

View 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.

Gene2Phenotype Curations

CACNA1B-related neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements

MIM #618497

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Rare variants in neuronal excitability genes influence risk for bipolar disorder.
Ament SA et al.·Proc Natl Acad Sci U S A
2015
Fine-mapping genomic loci refines bipolar disorder risk genes.
Koromina M et al.·Nat Neurosci
2025
CACNA1B (Ca(v)2.2) Overexpression and Its Association with Clinicopathologic Characteristics and Unfavorable Prognosis in Non-Small Cell Lung Cancer.
Zhou X et al.·Dis Markers
2017
Pharmacogenetics of new analgesics.
Lötsch J et al.·Br J Pharmacol
2011Review
The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort.
Mencacci NE et al.·Hum Mol Genet
2015Cohort
A Clinical and Integrated Genetic Study of Isolated and Combined Dystonia in Taiwan.
Wu MC et al.·J Mol Diagn
2022
High expression of N-type calcium channel indicates a favorable prognosis in gliomas.
Li G et al.·Medicine (Baltimore)
2022
Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.
Gorman KM et al.·Am J Hum Genet
2019
CACNA1B gene variants in adult-onset isolated focal dystonia.
Cocoș R et al.·Neurol Sci
2021
DNA methylation and 28 year incidence of two neuropathy phenotypes in type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications cohort study.
Zhou J et al.·Diabetologia
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Trpv1-dependent Cacna1b gene inactivation reveals cell-specific functions of CaV2.2 channels in vivo.
Meir RY et al.·Channels (Austin)
2026🔓 Open Access
Clinical features and genetic analysis of developmental and epileptic encephalopathy caused by biallelic variants of CACNA1B.
Yu XY et al.·Heliyon
2024🔓 Open Access
Identification of a de novo CACNA1B variant and a start-loss ADRA2B variant in paroxysmal kinesigenic dyskinesia.
Yuan Z et al.·Heliyon
2024🔓 Open Access
CACNA1B protects naked mole-rat hippocampal neuron from apoptosis via altering the subcellular localization of Nrf2 after 60Co irradiation.
Yang W et al.·Cell Biol Int
2024
The Drosophila ortholog of the schizophrenia-associated CACNA1A and CACNA1B voltage-gated calcium channels regulate memory, sleep and circadian rhythms.
Hidalgo S et al.·Neurobiol Dis
2021
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools