GPR158
Chr 10G protein-coupled receptor 158
Also known as: mGlyR
GPR158 encodes a metabotropic glycine receptor that controls synapse formation and function in the brain by regulating G protein signaling and cAMP levels, particularly affecting neuronal excitability in the prefrontal cortex and hippocampus. Mutations cause autosomal recessive neurodevelopmental disorders characterized by intellectual disability, developmental delay, and behavioral abnormalities with childhood onset. This gene is highly constrained against loss-of-function variants (LOEUF 0.467), indicating that biallelic mutations likely cause severe phenotypes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
GPR158 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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