CACNB1

Chr 17

calcium voltage-gated channel auxiliary subunit beta 1

Also known as: CAB1, CACNLB1, CCHLB1

NCBI Gene: 782UniProt: Q02641

The protein encoded by this gene belongs to the calcium channel beta subunit family. It plays an important role in the calcium channel by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternative splicing occurs at this locus and three transcript variants encoding three distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

0
Active trials
90
ClinVar variants
9
Pathogenic / LP
2.1
Missense Z
0.38
LOEUF
4
Pubs (2 yr)
Clinical Summary— CACNB1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.79) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 72 VUS of 90 total submissions
Some data sources returned errors (2)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.38LOEUF
pLI 0.787
Z-score 4.21
OE 0.19 (0.10–0.38)
Moderately constrained

More LoF-intolerant than ~75% 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.
2.14Z-score
OE missense 0.69 (0.62–0.77)
260 obs / 376.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.19 (0.10–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.62–0.77)
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.0.80
0≤1.21.6
LoF obs/exp: 6 / 31.5Missense obs/exp: 260 / 376.8Syn Z: 1.97

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS72
Likely Benign7
Benign2
9
Pathogenic
72
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
7
0
9
Likely Pathogenic
0
0
0
0
0
VUS
0
67
5
0
72
Likely Benign
0
1
2
4
7
Benign
0
0
0
2
2
Total26814690

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

View in ClinVar →

Protein Context — Lollipop Plot

CACNB1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of CACNB1 protein as an actionable therapeutic target for hepatocellular carcinoma via metabolic dysfunction analysis in liver diseases: An integrated bioinformatics and machine learning approach for precise therapy.
Sun J et al.·Int J Biol Macromol
2025
Functional and structural characterization of a novel malignant hyperthermia-susceptible variant of DHPR-β(1a) subunit (CACNB1).
Perez CF et al.·Am J Physiol Cell Physiol
2018Functional
N-terminal truncating variants in CACNB1 cause a new congenital muscular disorder.
Iturrate A et al.·Eur J Hum Genet
2026
Validation of L-type calcium channel blocker amlodipine as a novel ADHD treatment through cross-species analysis, drug-target Mendelian randomization, and clinical evidence from medical records.
Þorsteinsson H et al.·Neuropsychopharmacology
2025
MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation.
Lu Y et al.·Circulation
2010Functional
Inhibitory effects on L- and N-type calcium channels by a novel Ca(V)β(1) variant identified in a patient with autism spectrum disorder.
Despang P et al.·Naunyn Schmiedebergs Arch Pharmacol
2022Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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

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