P2RY12: Purinergic Receptor P2Y12 – Platelet ADP Receptor and Antithrombotic Drug Target
A comprehensive biomedical overview of the P2RY12 gene, its protein product, expression, mutations, and clinical significance in thrombosis and beyond.
Gene Information Card
| Symbol | P2RY12 |
|---|---|
| Full Name | Purinergic Receptor P2Y12 |
| Gene Type | protein coding |
| Chromosomal Location | 3q25.1 |
| NCBI Gene ID | 64805 ncbi.nlm.nih.gov/gene/64805 |
| Ensembl ID | ENSG00000169313 |
| UniProt ID | Q9H244 |
| OMIM ID | 600515 |
| HGNC ID | 18124 |
| Aliases | ADPG-R, P2T(ADP), P2Y12, SP1999 |
Description
P2RY12 encodes the P2Y12 receptor, a G protein-coupled receptor (GPCR) that is primarily expressed on platelets and plays a critical role in platelet activation and aggregation. It is activated by adenosine diphosphate (ADP) and is a major target for antiplatelet drugs such as clopidogrel and ticagrelor. Beyond platelets, P2RY12 is also expressed in microglia and certain immune cells, where it modulates inflammatory responses. Mutations in P2RY12 can lead to bleeding disorders, and its expression is altered in various cancers and neurological conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bleeding disorder, platelet-type 8 | Loss-of-function mutations impair ADP-induced platelet aggregation, leading to prolonged bleeding. | ClinVar; OMIM #600515 |
| Thrombotic disorders (e.g., myocardial infarction, stroke) | Gain-of-function variants may enhance platelet reactivity, increasing thrombotic risk. | Literature; ClinVar |
| Cancer (e.g., breast, lung, colorectal) | P2RY12 expression in tumor cells and tumor microenvironment may promote metastasis and immune evasion. | COSMIC; PubMed |
| Neuroinflammation (e.g., Alzheimer's disease, multiple sclerosis) | P2RY12 on microglia mediates chemotaxis and phagocytosis; altered expression is linked to neuroinflammatory states. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood (platelets) | High | Predominant expression |
| Spleen | Moderate | Immune cells |
| Brain (microglia) | Moderate | Glial cells |
| Lung | Low | Alveolar macrophages |
| Liver | Low | Kupffer cells |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | Low | Transfected for functional studies |
| THP-1 (monocytic) | Moderate | Monocyte/macrophage lineage |
| HUVEC (endothelial) | Low | Endothelial cells |
| Platelets (primary) | High | Native expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.136C>T (p.Arg46Trp) | Missense | Rare | Loss of function; impaired ADP binding |
| c.250G>A (p.Gly84Asp) | Missense | Rare | Loss of function; reduced surface expression |
| c.412C>T (p.Arg138Cys) | Missense | Rare | Loss of function; defective signaling |
| c.893C>T (p.Pro298Leu) | Missense | Rare | Loss of function; altered receptor conformation |
| c.1000G>A (p.Gly334Ser) | Missense | Rare | Loss of function; impaired G protein coupling |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations are loss-of-function, leading to defective ADP-induced platelet aggregation and bleeding diathesis.
Gain of Function (GOF)
Gain-of-function variants are less common but may increase platelet reactivity and thrombotic risk; specific variants are under investigation.
Dominant Negative (DN)
No clear dominant-negative mutations have been reported; P2RY12 is a monomeric GPCR, and loss-of-function is typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • ADP receptor activity |
| • signal transduction | • platelet activation |
| • cell surface receptor signaling pathway | • inflammatory response |
| • microglial cell activation |
Pathways
• ADP signaling through P2Y12 receptor
• GPCR downstream signaling
• Platelet aggregation pathway
• G alpha i signaling events
Protein Summary
The P2Y12 protein is a 342-amino acid GPCR with seven transmembrane domains. It couples to Gi proteins, inhibiting adenylate cyclase and activating PI3K pathways, leading to platelet activation and aggregation. It is the target of thienopyridine and cyclopentyl-triazolopyrimidine antiplatelet drugs. In microglia, P2Y12 mediates chemotaxis and process extension. The protein is also implicated in cancer progression and immune modulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| P2RY12 Knockout HEK293 Cell Line | EDJ-KQ51631 | Human | 64805 | Details Get a Quote |
| P2RY12 Knockout HeLa Cell Line | EDJ-KQ57083 | Human | 64805 | Details Get a Quote |
| P2RY12 Knockout A-549 Cell Line | EDJ-KQ65595 | Human | 64805 | Details Get a Quote |
| P2RY12 Knockout HCT 116 Cell Line | EDJ-KQ74024 | Human | 64805 | Details Get a Quote |
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