CACNA2D4

Chr 12AR

calcium voltage-gated channel auxiliary subunit alpha2delta 4

Also known as: RCD4

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Retinal cone dystrophy 4MIM #610478
AR
0
Active trials
1
Pubs (1 yr)
13
P/LP submissions
0%
P/LP missense
1.01
LOEUF
LOF
Mechanism· G2P
Clinical SummaryCACNA2D4
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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· 370 VUS of 600 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.47
OE 0.82 (0.661.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.75Z-score
OE missense 0.92 (0.860.98)
628 obs / 683.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.82 (0.661.01)
00.351.4
Missense OE0.92 (0.860.98)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 60 / 73.6Missense obs/exp: 628 / 683.3Syn Z: 0.41

ClinVar Variant Classifications

600 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic3
VUS370
Likely Benign202
Conflicting5
10
Pathogenic
3
Likely Pathogenic
370
VUS
202
Likely Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
9
0
10
Likely Pathogenic
1
0
2
0
3
VUS
20
301
46
3
370
Likely Benign
0
5
96
101
202
Benign
0
0
0
0
0
Conflicting
5
Total22306153104590

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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