CACNA1D

Chr 3ADAR

calcium voltage-gated channel subunit alpha1 D

Also known as: CACH3, CACN4, CACNL1A2, CCHL1A2, Cav1.3, PASNA, SANDD

NCBI Gene: 776ENSG00000157388UniProt: Q01668OMIM: 114206

Voltage-dependent calcium channels 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, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Primary aldosteronism, seizures, and neurologic abnormalitiesMIM #615474
AD
Sinoatrial node dysfunction and deafnessMIM #614896
AR

Clinical highlights

Gene-disease validity (ClinGen)
sinoatrial node dysfunction and deafness · ARModerateconsider for supplementary testing2 gene-disease associations curated in total
Interpreting a novel variant
Both gain of function and loss of function mechanisms are described for this gene and which one applies is variant-dependent. Do not assume a null variant is — or isn't — the pathogenic class without checking the specific variant against curated evidence.Curated gene-level mechanism — a prior for triage, not a per-variant call.
2
Active trials
73
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.21
LOEUF· LoF intol.
GOF/LOF*
Mechanism· annotated
📖
GeneReview available — CACNA1D
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.21LOEUF
pLI 1.000
Z-score 8.67
OE 0.14 (0.10–0.21)
Highly constrained

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

Missense Constraint?
4.58Z-score
OE missense 0.64 (0.60–0.67)
797 obs / 1253.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.14 (0.10–0.21)
0≤0.351.4
Missense OE?0.64 (0.60–0.67)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
LoF obs/exp: 17 / 119.1Missense obs/exp: 797 / 1253.5Syn Z: -0.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CACNA1D · 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