CACNA2D3

Chr 3

calcium voltage-gated channel auxiliary subunit alpha2delta 3

Also known as: HSA272268

The alpha-2/delta-3 subunit regulates calcium current density and activation/inactivation kinetics of voltage-dependent calcium channels, specifically P/Q-type, N-type, and L-type calcium channels in the nervous system. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.34
Clinical SummaryCACNA2D3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.578
Z-score 5.99
OE 0.22 (0.140.34)
Highly constrained

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

Missense Constraint
1.86Z-score
OE missense 0.78 (0.720.84)
451 obs / 576.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.140.34)
00.351.4
Missense OE0.78 (0.720.84)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 15 / 68.5Missense obs/exp: 451 / 576.9Syn Z: -0.08

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CACNA2D3 · 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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