CACNA2D2

Chr 3

calcium voltage-gated channel auxiliary subunit alpha2delta 2

Also known as: CACNA2D, CASVDD

NCBI Gene: 9254ENSG00000007402UniProt: Q9NY47

Calcium channels mediate the entry of calcium ions into the cell upon membrane polarization. This gene encodes the alpha-2/delta subunit of the voltage-dependent calcium channel complex. The complex consists of the main channel-forming subunit alpha-1, and auxiliary subunits alpha-2/delta, beta, and gamma. The auxiliary subunits function in the assembly and membrane localization of the complex, and modulate calcium currents and channel activation/inactivation kinetics. The subunit encoded by this gene undergoes post-translational cleavage to yield the extracellular alpha2 peptide and a membrane-anchored delta polypeptide. This subunit is a receptor for the antiepileptic drug, gabapentin. Mutations in this gene are associated with early infantile epileptic encephalopathy. Single nucleotide polymorphisms in this gene are correlated with increased sensitivity to opioid drugs. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCerebellar atrophy with seizures and variable developmental delay

Clinical highlights

Gene-disease validity (ClinGen)
complex neurodevelopmental disorder · ARModerateconsider for supplementary testing
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.Based on population constraint only.
0
Active trials
23
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.23
LOEUF· LoF intol.
—
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.23LOEUF
pLI 1.000
Z-score 6.89
OE 0.14 (0.08–0.23)
Highly constrained

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

Missense Constraint?
3.00Z-score
OE missense 0.67 (0.61–0.72)
426 obs / 639.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.14 (0.08–0.23)
0≤0.351.4
Missense OE?0.67 (0.61–0.72)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 10 / 74.0Missense obs/exp: 426 / 639.5Syn Z: -0.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CACNA2D2 · 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