RGS3
Chr 9regulator of G protein signaling 3
Also known as: C2PA, RGP3
The protein is a GTPase-activating protein that down-regulates G-protein signaling by increasing GTPase activity of G-alpha subunits, driving them into their inactive GDP-bound form. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by seizures, developmental delay, and intellectual disability. The gene is highly constrained against loss-of-function variants (pLI near 0, LOEUF 0.645), indicating that complete loss of protein function is likely not tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
RGS3 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools