CACNA1G
Chr 17ADcalcium voltage-gated channel subunit alpha1 G
Also known as: Ca(V)T.1, Cav3.1, NBR13, SCA42, SCA42ND
This gene encodes the alpha-1G subunit of T-type voltage-gated calcium channels, which generate low-threshold calcium currents essential for neuronal pacemaking, oscillations, and burst firing patterns. Mutations cause spinocerebellar ataxia 42 through an autosomal dominant inheritance pattern, with early-onset variants associated with severe neurodevelopmental deficits. The gene is highly constrained against loss-of-function variants, and mutations can cause disease predominantly through gain-of-function mechanisms that likely disrupt normal neuronal calcium signaling.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
Cav3.1 (T-type) alpha subunit. Monoallelic pathogenic variants cause GOF with shifted voltage dependence and increased window current. G2P classifies as LOF, but electrophysiology data demonstrate gain-of-function at the channel level.
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CACNA1G · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools