P2RY8
Chr YP2Y receptor family member 8
Also known as: P2Y8
P2RY8 encodes a G protein-coupled receptor for S-geranylgeranyl-glutathione that regulates lymphocyte positioning and growth within lymphoid organs by coupling to GNA13 signaling and repressing AKT activation. Mutations cause agammaglobulinemia 4, an autosomal recessive primary immunodeficiency characterized by absent or severely reduced immunoglobulins and B cells. The gene has low constraint against loss-of-function variants (pLI 0.003), consistent with the recessive inheritance pattern requiring biallelic mutations for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
37 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 33 |
Likely Pathogenic | — | — | — | — | 0 |
VUS | — | — | — | — | 3 |
Likely Benign | — | — | — | — | 0 |
Benign | — | — | — | — | 1 |
| Total | — | 37 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
P2RY8 · 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