CACNG3

Chr 16

calcium voltage-gated channel auxiliary subunit gamma 3

NCBI Gene: 10368 ENSG00000006116 UniProt: O60359 OMIM: 606403

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a type I transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family. This gene is a susceptibility locus for childhood absence epilepsy. [provided by RefSeq, Dec 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.20

Clinical Summary— CACNG3

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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.

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ClinVar Variants

19 VUS of 19 total submissions

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?

0.20LOEUF

pLI 0.994

Z-score 3.62

OE 0.00 (0.00–0.20)

Highly constrained

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

Missense Constraint?

2.64Z-score

OE missense 0.47 (0.40–0.56)

95 obs / 200.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.20)

0≤0.351.4

Missense OE?0.47 (0.40–0.56)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 0 / 15.3Missense obs/exp: 95 / 200.3Syn Z: -0.87

This gene — mechanism propensity

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

19 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	18	19
Likely Benign	0	0	0
Benign	0	0	0
Total	1	18	19

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap CACNG3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →