P2RY12

Chr 3AR

purinergic receptor P2Y12

Also known as: ADPG-R, BDPLT8, HORK3, P2T(AC), P2Y(12)R, P2Y(AC), P2Y(ADP), P2Y(cyc)

NCBI Gene: 64805ENSG00000169313UniProt: Q9H244

The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

Bleeding disorder, platelet-type, 8MIM #609821
AR
149
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— P2RY12
🧬
Gene-Disease Validity (ClinGen)
platelet-type bleeding disorder 8 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 94 VUS of 149 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.41LOEUF
pLI 0.002
Z-score 0.82
OE 0.68 (0.35–1.41)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.86Z-score
OE missense 0.82 (0.72–0.94)
152 obs / 185.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.35–1.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.72–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 5 / 7.4Missense obs/exp: 152 / 185.0Syn Z: 0.18

ClinVar Variant Classifications

149 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic8
VUS94
Likely Benign16
Benign10
Conflicting2
19
Pathogenic
8
Likely Pathogenic
94
VUS
16
Likely Benign
10
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
15
0
19
Likely Pathogenic
2
2
4
0
8
VUS
1
80
13
0
94
Likely Benign
0
7
4
5
16
Benign
0
2
4
4
10
Conflicting
—2
Total692409149

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bleeding disorder, platelet-type, 8

MIM #609821

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Transcriptome sequencing and Mendelian randomization analysis identified biomarkers related to neutrophil extracellular traps in diabetic retinopathy.
Hao L et al.·Front Immunol
2024
Association between P2RY12 gene polymorphisms and adverse clinical events in coronary artery disease patients treated with clopidogrel: A systematic review and meta-analysis.
Li JL et al.·Gene
2018Meta-analysis
Multiomics insights into BMI-related intratumoral microbiota in gastric cancer.
Liu K et al.·Front Cell Infect Microbiol
2025
CD73 inhibitor AB680 suppresses glioblastoma in mice by inhibiting purine metabolism and promoting P2RY12(+) microglia transformation.
Gao PP et al.·Acta Pharmacol Sin
2025
Neuroprotective role of geniposide-loaded UMSC nanovesicles in depression via P2ry12 downregulation.
Duan G et al.·Phytomedicine
2025
P2Y12 receptors: structure and function.
Cattaneo M·J Thromb Haemost
2015Review
An adapted protocol to derive microglia from stem cells and its application in the study of CSF1R-related disorders.
Dorion MF et al.·Mol Neurodegener
2024
P2RY12:rs7637803 TT variant genotype increases coronary artery aneurysm risk in Kawasaki disease in a southern Chinese population.
Lu Z et al.·J Gene Med
2019
Prognostic value and immune infiltration of a novel stromal/immune score-related P2RY12 in lung adenocarcinoma microenvironment.
Yu L et al.·Int Immunopharmacol
2021
Impact of Y chromosome loss on the risk of Parkinson's disease and progression.
Wang J et al.·EBioMedicine
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cardiovascular Disease (CVD)StrokeAcute Coronary Syndrome

A Genomic Approach for Clopidogrel in Caribbean Hispanics

ACTIVE NOT RECRUITING
NCT03419325Phase EARLY_PHASE1University of Puerto RicoStarted 2020-09-01
CYP2C19 testP2RY12 assay
Coronary Disease

Genetic Polymorphism Associated With Coronary Heart Disease Susceptibility and Variability of Clopidogrel Response

ACTIVE NOT RECRUITING
NCT03373552Hôpital Universitaire Fattouma BourguibaStarted 2015-08-12
Platelet function assay

External Resources

Links to major genomics databases and tools