GPSM1
Chr 9G protein signaling modulator 1
Also known as: AGS3
The protein functions as a guanine nucleotide dissociation inhibitor that keeps G(i/o) alpha subunits in their GDP-bound state and controls spindle orientation and asymmetric cell fate in cerebral cortical progenitors. Mutations cause autosomal recessive Chudley-McCullough syndrome, characterized by early-onset sensorineural hearing loss and brain malformations including polymicrogyria and cerebellar hypoplasia. The gene is highly intolerant to loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.
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
GPSM1 · 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