CACNA2D4

Chr 12AR

calcium voltage-gated channel auxiliary subunit alpha2delta 4

Also known as: RCD4

NCBI Gene: 93589ENSG00000151062UniProt: Q7Z3S7OMIM: 608171

The alpha-2/delta-4 subunit regulates calcium current density and activation/inactivization kinetics of voltage-dependent calcium channels, which mediate calcium influx upon membrane depolarization. Biallelic mutations cause retinal cone dystrophy 4, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, indicating intolerance to haploinsufficiency in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.011 OMIM phenotype
Clinical Summary— CACNA2D4
🧬
Gene-Disease Validity (ClinGen)
CACNA2D4-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 302 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.47
OE 0.82 (0.66–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.75Z-score
OE missense 0.92 (0.86–0.98)
628 obs / 683.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.82 (0.66–1.01)
0≤0.351.4
Missense OE0.92 (0.86–0.98)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 60 / 73.6Missense obs/exp: 628 / 683.3Syn Z: 0.41

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS302
Likely Benign175
10
Pathogenic
3
Likely Pathogenic
302
VUS
175
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
8
0
10
Likely Pathogenic
1
0
2
0
3
VUS
25
237
37
3
302
Likely Benign
0
6
90
79
175
Benign
0
0
0
0
0
Total2824313782490

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CACNA2D4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients