P2RY2

Chr 11

purinergic receptor P2Y2

Also known as: HP2U, P2RU1, P2U, P2U1, P2UR, P2Y2, P2Y2R

NCBI Gene: 5029 ENSG00000175591 UniProt: P41231

The P2RY2 protein is a G-protein coupled receptor that binds ATP and UTP to activate phosphatidylinositol-calcium second messenger pathways involved in cellular proliferation, apoptosis, and inflammation. Mutations in this gene cause autosomal recessive congenital stationary night blindness and autosomal recessive cone dystrophy. The gene shows tolerance to loss-of-function variants (pLI=0.08, LOEUF=0.91), consistent with recessive inheritance patterns affecting retinal function.

ResearchSummary from RefSeq, UniProt

The product of this gene belongs to the family of P2 receptors, which is activated by extracellular nucleotides and subdivided into P2X ligand-gated ion channels and P2Y 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, found on many cell types, is activated by ATP and UTP and is reported to be overexpressed on some cancer cell types. It is involved in many cellular functions, such as proliferation, apoptosis and inflammation. Three transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Mar 2013]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.084

Z-score 1.75

OE 0.35 (0.16–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.20Z-score

OE missense 0.97 (0.87–1.07)

265 obs / 274.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.16–0.91)

0≤0.351.4

Missense OE?0.97 (0.87–1.07)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 3 / 8.5Missense obs/exp: 265 / 274.2Syn Z: 0.45

Background carrier burden — how many people carry a rare variant somewhere in P2RY2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

604 rare PASS variants

Rare truncating (LoF)

1 in 1,700

69 rare PASS variants

Rare synonymous (reference)

1 in 140

258 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for P2RY2. 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 90	1 in 2,200
South Asian	~43k	1 in 140	1 in 2,300
Remaining (unassigned)	~30k	1 in 72	1 in 2,700
European (Finnish)	~27k	1 in 410	≈ 1 in 6,200
Admixed American	~22k	1 in 110	1 in 1,600
African / African American	~21k	1 in 100	1 in 1,400
East Asian	~20k	1 in 98	1 in 1,100
Ashkenazi Jewish	~13k	1 in 310	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 140	1 in 480

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 ↓