P2RY12
Chr 3ARpurinergic receptor P2Y12
This gene encodes a G-protein coupled receptor for ADP and ATP that inhibits adenylyl cyclase and is required for normal platelet aggregation and blood coagulation. Mutations cause bleeding disorder, platelet-type 8, an autosomal recessive condition affecting hemostasis. The gene is not highly constrained against loss-of-function variants (pLI = 0.002, LOEUF = 1.41), consistent with its recessive inheritance pattern.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Some data sources returned errors (1)
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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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
P2RY12 · 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
A Genomic Approach for Clopidogrel in Caribbean Hispanics
ACTIVE NOT RECRUITINGGenetic Polymorphism Associated With Coronary Heart Disease Susceptibility and Variability of Clopidogrel Response
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools