P2RY2

Chr 11

purinergic receptor P2Y2

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

NCBI Gene: 5029ENSG00000175591UniProt: P41231

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]

85
ClinVar variants
8
Pathogenic / LP
0.08
pLI score
0
Active trials
Clinical Summary— P2RY2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.08) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 71 VUS of 85 total submissions

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.
0.91LOEUF
pLI 0.084
Z-score 1.75
OE 0.35 (0.16–0.91)
Tolerant

Typical tolerance to LoF variation

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.
0.20Z-score
OE missense 0.97 (0.87–1.07)
265 obs / 274.2 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.0.35 (0.16–0.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.87–1.07)
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.0.95
0≤1.21.6
LoF obs/exp: 3 / 8.5Missense obs/exp: 265 / 274.2Syn Z: 0.45

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS71
Likely Benign5
Benign1
8
Pathogenic
71
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
1
68
2
0
71
Likely Benign
0
5
0
0
5
Benign
0
0
0
1
1
Total17310185

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

View in ClinVar →

Protein Context — Lollipop Plot

P2RY2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Circulating Naturally Occurring Antibodies to P2RY2 Are Decreased in Alzheimer's Disease.
Jian JM et al.·J Alzheimers Dis
2022
Upregulation of has_circ_0008389 promotes esophageal squamous cell carcinoma progression via miR-761 sponging and P2RY2 mRNA stabilization.
Shao Z et al.·Int J Biol Macromol
2025
The P2RY2 Receptor Induces Carcinoma Cell Migration and EMT Through Cross-Talk With Epidermal Growth Factor Receptor.
Martínez-Ramírez AS et al.·J Cell Biochem
2016
Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans.
Lessard CJ et al.·Arthritis Rheumatol
2016
Purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene is associated with cerebral infarction in Japanese subjects.
Wang Z et al.·Hypertens Res
2009
P2X7 receptor in macrophage polarization and its implications in neuroblastoma tumor behavior.
Bento CA et al.·Purinergic Signal
2025
Molecular Signaling and Dysfunction of the Human Reactive Enteric Glial Cell Phenotype: Implications for GI Infection, IBD, POI, Neurological, Motility, and GI Disorders.
Liñán-Rico A et al.·Inflamm Bowel Dis
2016
Comprehensive analysis of microglia gene and subpathway signatures for glioma prognosis and drug screening: linking microglia to glioma.
Zhang C et al.·J Transl Med
2022
Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets.
Maiga A et al.·Blood Cancer J
2016
Screening pathogenic genes in oral squamous cell carcinoma based on the mRNA expression microarray data.
Ding Y et al.·Int J Mol Med
2018
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools