CACNA1F

Chr X

calcium voltage-gated channel subunit alpha1 F

Also known as: AIED, COD3, COD4, CORDX, CORDX3, CSNB2, CSNB2A, CSNBX2

This gene encodes a multipass transmembrane protein that functions as an alpha-1 subunit of the voltage-dependent calcium channel, which mediates the influx of calcium ions into the cell. The encoded protein forms a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Mutations in this gene can cause X-linked eye disorders, including congenital stationary night blindness type 2A, cone-rod dystropy, and Aland Island eye disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2013]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.45
Clinical SummaryCACNA1F
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Gene-Disease Validity (ClinGen)
CACNA1F-related retinopathy · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.45LOEUF
pLI 0.000
Z-score 5.40
OE 0.32 (0.230.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.60Z-score
OE missense 0.75 (0.700.80)
632 obs / 844.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.32 (0.230.45)
00.351.4
Missense OE?0.75 (0.700.80)
00.61.4
Synonymous OE?0.89
01.21.6
LoF obs/exp: 23 / 72.7Missense obs/exp: 632 / 844.7Syn Z: 1.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCACNA1F-related Aland Island eye diseaseLOFXLR

This gene — mechanism propensity

DN
0.79top 25%
GOF
0.85top 5%
LOF
0.2189th %ile

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.

GOFprediction above median
DNprediction above median

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.

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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