CACNA1H
Chr 16ADcalcium voltage-gated channel subunit alpha1 H
Also known as: CACNA1HB, Cav3.2, ECA6, EIG6, HALD4
The protein forms the pore-forming alpha-1 subunit of voltage-dependent T-type calcium channels, controlling calcium ion influx into cells upon membrane depolarization. Mutations cause childhood absence epilepsy, idiopathic generalized epilepsy, and familial hyperaldosteronism type IV through an autosomal dominant inheritance pattern. The pathogenic mechanism involves gain-of-function effects that disrupt normal calcium channel activity.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). 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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CACNA1H · 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
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGEfficacy Study of a Food Supplement With Myo-inositol, N-Acetyl-Cystein, Zinc and Vitamins on Sperm DNA Fragmentation
RECRUITINGExternal Resources
Links to major genomics databases and tools