CACNA2D1

Chr 7

calcium voltage-gated channel auxiliary subunit alpha2delta 1

Also known as: CACNA2, CACNL2A, CCHL2A, DEE110, LINC01112, lncRNA-N3

NCBI Gene: 781ENSG00000153956UniProt: P54289

The preproprotein encoded by this gene is cleaved into multiple chains that comprise the alpha-2 and delta subunits of the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. Mutations in this gene can cause cardiac deficiencies, including Brugada syndrome and short QT syndrome. Alternate splicing results in multiple transcript variants, some of which may lack the delta subunit portion. [provided by RefSeq, Nov 2014]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 110

Clinical highlights

Gene-disease validity (ClinGen)
short QT syndrome · ADDisputedevidence questions this relationship2 gene-disease associations curated in total
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
32
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.24
LOEUF· LoF intol.
LOF
Mechanism· predicted
📖
GeneReview available — CACNA2D1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.24LOEUF
pLI 1.000
Z-score 6.81
OE 0.15 (0.09–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.49Z-score
OE missense 0.59 (0.54–0.64)
336 obs / 570.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.15 (0.09–0.24)
0≤0.351.4
Missense OE?0.59 (0.54–0.64)
0≤0.61.4
Synonymous OE?0.90
0≤1.21.6
LoF obs/exp: 11 / 74.4Missense obs/exp: 336 / 570.6Syn Z: 1.08

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CACNA2D1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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