CACNA1F
Chr XX-linkedXLRcalcium voltage-gated channel subunit alpha1 F
Also known as: AIED, COD3, COD4, CORDX, CORDX3, CSNB2, CSNB2A, CSNBX2
This gene encodes the alpha-1F subunit of voltage-sensitive L-type calcium channels that mediate calcium influx into excitable cells, particularly important for neurotransmitter release and cellular signaling. Mutations cause X-linked eye disorders including congenital stationary night blindness type 2A, cone-rod dystrophy, and Aland Island eye disease. The gene shows X-linked recessive inheritance and is highly constrained against loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative 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.
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
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 36 | 1 | 13 | 0 | 50 |
Likely Pathogenic | 21 | 2 | 1 | 0 | 24 |
VUS | 6 | 228 | 17 | 2 | 253 |
Likely Benign | 1 | 3 | 67 | 64 | 135 |
Benign | 0 | 0 | 3 | 0 | 3 |
Conflicting | — | 1 | |||
| Total | 64 | 234 | 101 | 66 | 466 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CACNA1F · 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