CACNA2D2

Chr 3AR

calcium voltage-gated channel auxiliary subunit alpha2delta 2

Also known as: CACNA2D, CASVDD

NCBI Gene: 9254ENSG00000007402UniProt: Q9NY47OMIM: 607082

The protein encodes the alpha-2/delta auxiliary subunit of voltage-dependent calcium channels, which undergoes post-translational cleavage and functions in channel assembly, membrane localization, and modulation of calcium currents and activation/inactivation kinetics. Autosomal recessive mutations cause early infantile epileptic encephalopathy with cerebellar atrophy, seizures, and variable developmental delay. The subunit serves as a receptor for the antiepileptic drug gabapentin.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.231 OMIM phenotype
Clinical Summary— CACNA2D2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Explore recent and relevant literature in Research Assistant →

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 OE0.14 (0.08–0.23)
0≤0.351.4
Missense OE0.67 (0.61–0.72)
0≤0.61.4
Synonymous OE1.03
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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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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
CACNA2D2 rs56287038:G>T and SCN1A rs2298771:C>T Variants Are Associated with Antiseizure Medication Response in Turkish Epilepsy Patients : A Pilot Study.
Todurga-Seven ZG et al.·Neuropsychobiology
2026Cohort
A CACNA2D2-Related Recessive Form of Cerebellar Abiotrophy in Angus Cattle.
Jacinto J et al.·Anim Genet
2026Open Access
iPSC screening identifies CACNA2D2 as a potential therapeutic target for FTLD-Tau.
Imamura K et al.·Eur J Cell Biol
2025
A biallelic mutation in CACNA2D2 associated with developmental and epileptic encephalopathy affects calcium channel-dependent as well as synaptic functions of α2δ-2.
Haddad S et al.·J Neurochem
2025Open Access
Circular RNA circMYLK4 shifts energy metabolism from glycolysis to OXPHOS by binding to the calcium channel auxiliary subunit CACNA2D2.
Cao H et al.·J Biol Chem
2024Open Access
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