CACNG2
Chr 22ADcalcium voltage-gated channel auxiliary subunit gamma 2
Also known as: MRD10
CACNG2 encodes a transmembrane AMPA receptor regulatory protein (TARP) that controls trafficking and gating properties of AMPA-selective glutamate receptors, which mediate fast excitatory neurotransmission and are crucial for synaptic plasticity, learning and memory. Mutations cause autosomal dominant intellectual developmental disorder. This gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.38), suggesting intolerance to protein disruption.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
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
97 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 16 | 0 | 16 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 3 | 49 | 11 | 1 | 64 |
Likely Benign | 0 | 1 | 3 | 7 | 11 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 3 | 50 | 31 | 9 | 93 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CACNG2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools