CACNB1

Chr 17

calcium voltage-gated channel auxiliary subunit beta 1

Also known as: CAB1, CACNLB1, CCHLB1

NCBI Gene: 782 ENSG00000067191 UniProt: Q02641 OMIM: 114207

The calcium channel beta-1 subunit regulates L-type calcium channels by modulating peak calcium current, controlling membrane targeting of alpha subunits, and shifting voltage dependence of activation and inactivation. Mutations cause autosomal dominant episodic ataxia and developmental and epileptic encephalopathy with onset in infancy to childhood, affecting neurological function. This gene shows significant constraint against loss-of-function variants (LOEUF 0.376), indicating that complete loss of protein function is likely not well tolerated.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.38

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.19 (0.10–0.38)

0≤0.351.4

Missense OE?0.69 (0.62–0.77)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 6 / 31.5Missense obs/exp: 260 / 376.8Syn Z: 1.97

Background carrier burden — how many people carry a rare variant somewhere in CACNB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

761 rare PASS variants

Rare truncating (LoF)

1 in 2,900

81 rare PASS variants

Rare synonymous (reference)

1 in 160

356 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CACNB1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 2,600
South Asian	~43k	1 in 74	1 in 2,500
Remaining (unassigned)	~30k	1 in 110	1 in 3,100
European (Finnish)	~27k	1 in 170	≈ 1 in 13,000
Admixed American	~22k	1 in 93	≈ 1 in 11,000
African / African American	~21k	1 in 90	1 in 3,300
East Asian	~20k	1 in 130	≈ 1 in 4,500
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 4,100
Middle Eastern	~2,884	1 in 92	≈ 1 in 2,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 14 coding exons well covered in gnomAD exomes; exons 1, 9 marginal. Genomes: all 14.? see exons ↓