CACNB2
Chr 10ADcalcium voltage-gated channel auxiliary subunit beta 2
Also known as: CAB2, CACNLB2, CAVB2, MYSB
This gene encodes a beta subunit of voltage-dependent calcium channels that increases peak calcium current and modulates channel activation and inactivation, particularly contributing to beta-adrenergic regulation of heart rate and contractile force in cardiomyocytes. Mutations cause Brugada syndrome 4, a cardiac arrhythmia disorder with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI nearly 1.0), indicating that complete loss of function is likely incompatible with survival.
Primary Disease Associations & Inheritance
Disputed — evidence questions this relationship
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 3 | 0 | 3 |
Likely Pathogenic | 1 | 0 | 0 | 0 | 1 |
VUS | 9 | 239 | 30 | 3 | 281 |
Likely Benign | 2 | 5 | 70 | 119 | 196 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 1 | |||
| Total | 12 | 244 | 105 | 122 | 484 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CACNB2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools