CACNB4

Chr 2AD

calcium voltage-gated channel auxiliary subunit beta 4

Also known as: CAB4, CACNLB4, EA5, EIG9, EJM, EJM4, EJM6

NCBI Gene: 785ENSG00000182389UniProt: O00305OMIM: 601949

This gene encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. The protein encoded by this locus plays an important role in calcium channel function 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. Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE), juvenile myoclonic epilepsy (JME), and episodic ataxia, type 5. [provided by RefSeq, Aug 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Episodic ataxia, type 5MIM #613855
AD
{Epilepsy, idiopathic generalized, susceptibility to, 9}MIM #607682
AD
{Epilepsy, juvenile myoclonic, susceptibility to, 6}MIM #607682
AD
UniProtEpisodic ataxia 5

Clinical highlights

Gene-disease validity (ClinGen)
epilepsy · ADRefutedevidence has disproved this relationship
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
12
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.49
LOEUF
LOF*
Mechanism· G2P
📖
GeneReview available — CACNB4
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.49LOEUF
pLI 0.031
Z-score 3.77
OE 0.28 (0.17–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.69Z-score
OE missense 0.55 (0.49–0.63)
161 obs / 290.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.28 (0.17–0.49)
0≤0.351.4
Missense OE?0.55 (0.49–0.63)
0≤0.61.4
Synonymous OE?0.89
0≤1.21.6
LoF obs/exp: 9 / 32.0Missense obs/exp: 161 / 290.2Syn Z: 0.86

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CACNB4 · 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

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