CACNA2D1

Chr 7AR

calcium voltage-gated channel auxiliary subunit alpha2delta 1

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

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics, playing an important role in excitation-contraction coupling. Mutations cause autosomal recessive developmental and epileptic encephalopathy 110. This gene is highly constrained against loss-of-function variants (pLI >0.99), indicating that functional copies are essential for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.241 OMIM phenotype
Clinical SummaryCACNA2D1
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Gene-Disease Validity (ClinGen)
short QT syndrome · ADDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 6.81
OE 0.15 (0.090.24)
Highly constrained

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

Missense Constraint
3.49Z-score
OE missense 0.59 (0.540.64)
336 obs / 570.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.15 (0.090.24)
00.351.4
Missense OE0.59 (0.540.64)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 11 / 74.4Missense obs/exp: 336 / 570.6Syn Z: 1.08
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCACNA2D1-related short QT syndromeOTHERAD
limitedCACNA2D1-related Brugada syndromeOTHERAD
limitedCACNA2D1-related neurodevelopmental disorderOTHERAR
DN
0.3892th %ile
GOF
0.4678th %ile
LOF
0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

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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