CACNA1C (Q13936) variants and mutations

CACNA1C (also known as Q13936) is a human protein-coding gene encoding a voltage-dependent L-type calcium channel subunit alpha-1C protein. Its opening provides a major source of depolarization-triggered calcium entry in cardiomyocytes, smooth muscle, and neurons, coupling electrical activity to contraction and signaling. Pathogenic variants can cause Timothy syndrome, Brugada or long-QT phenotypes, and several neurodevelopmental disorders. This analysis covers 225 CACNA1C variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes Timothy syndrome, long QT syndrome 8, and hypertensive disorder. Example CACNA1C variants include V2D, V2L, and V2M.

Variant analysis overview

Gene: CACNA1C
Protein: Q13936
UniProt accession: Q13936
Organism: Homo sapiens
Variants analyzed: 225
Variant scope: all variants
Completed: 2026-08-20

Variant and mutation evidence

Variant composition: 67 unspecified-consequence records; 1 natural variant; 6 stop-gained variants; 108 missense variants; 29 synonymous variants; 9 frameshift variants; 2 splice-region variants; 3 substitution
Prediction scores: 174 variants have prediction scores (77% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Timothy syndrome, long QT syndrome 8, hypertensive disorder, Brugada syndrome 3, neurodevelopmental disorder with hypotonia, language delay, and skeletal defects, Brugada syndrome, Seizure, acquired long QT syndrome, epilepsy, diabetes mellitus, Hypertension, stroke disorder.

Protein structure and variant hotspots

Protein features: 24 transmembrane segments; 3 binding sites; 11 post-translational modification sites.
Structural context: 9 variants have structural context.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable CACNA1C variants

Examples include V2D, V2L, V2M, V2V, V2F, N3D, N3S, N3K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

CACNA1C analysis run — CACNA1C (225 variants) — completed 2026-08-20