CACNG3

Chr 16

calcium voltage-gated channel auxiliary subunit gamma 3

The protein encoded by CACNG3 is a transmembrane AMPA receptor regulatory protein (TARP) that regulates trafficking and gating properties of AMPA-selective glutamate receptors by promoting their targeting to synapses and modulating their activation, deactivation, and desensitization rates. Mutations in this gene are associated with childhood absence epilepsy, typically presenting in childhood. The gene is highly constrained against loss-of-function variants (pLI 0.99), indicating that such variants are likely to have significant clinical consequences.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.20
Clinical SummaryCACNG3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 23 VUS of 54 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 0.994
Z-score 3.62
OE 0.00 (0.000.20)
Highly constrained

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

Missense Constraint
2.64Z-score
OE missense 0.47 (0.400.56)
95 obs / 200.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.20)
00.351.4
Missense OE0.47 (0.400.56)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 0 / 15.3Missense obs/exp: 95 / 200.3Syn Z: -0.87
DN
0.4983th %ile
GOF
0.6053th %ile
LOF
0.70top 10%

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

LOFprediction above median · LOEUF 0.20

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

54 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS23
27
Pathogenic
3
Likely Pathogenic
23
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
3
0
3
VUS
1
18
4
0
23
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total11834053

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CACNG3 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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