CACNA1D

Chr 3

calcium voltage-gated channel subunit alpha1 D

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

NCBI Gene: 776 ENSG00000157388 UniProt: Q01668

The CACNA1D protein forms the pore-forming alpha-1D subunit of voltage-dependent calcium channels that mediate calcium entry into excitable cells for muscle contraction, hormone/neurotransmitter release, and gene expression. Mutations cause primary aldosteronism with seizures and neurologic abnormalities, as well as sinoatrial node dysfunction and deafness, through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves gain-of-function mutations that alter normal calcium channel activity.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSinoatrial node dysfunction and deafness

UniProtPrimary aldosteronism, seizures, and neurologic abnormalities

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.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.21

LOEUF· LoF intol.

GOF/LOF*

Mechanism· annotated

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GeneReview available — CACNA1D