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: 64805 ENSG00000169313 UniProt: Q9H244 OMIM: 600515

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bleeding disorder, platelet-type, 8MIM #609821

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.41

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.86Z-score

OE missense 0.82 (0.72–0.94)

152 obs / 185.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.35–1.41)

0≤0.351.4

Missense OE?0.82 (0.72–0.94)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 5 / 7.4Missense obs/exp: 152 / 185.0Syn Z: 0.18

Background carrier burden — how many people carry a rare variant somewhere in P2RY12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

386 rare PASS variants

Rare truncating (LoF)

1 in 4,500

51 rare PASS variants

Rare synonymous (reference)

1 in 360

159 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for P2RY12. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 370	1 in 6,200
South Asian	~43k	1 in 150	1 in 1,400
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 7,500
European (Finnish)	~27k	1 in 420	none seen
Admixed American	~22k	1 in 150	1 in 3,200
African / African American	~21k	1 in 130	1 in 3,100
East Asian	~20k	1 in 250	1 in 2,200
Ashkenazi Jewish	~13k	≈ 1 in 2,600	none seen
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓