P2RY6

Chr 11

pyrimidinergic receptor P2Y6

Also known as: P2Y6

NCBI Gene: 5031ENSG00000171631UniProt: Q15077

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, which is a G-protein coupled receptor, is responsive to UDP, partially responsive to UTP and ADP, and not responsive to ATP. It is proposed that this receptor mediates inflammatory responses. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Mar 2013]

17
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— P2RY6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 3 VUS of 17 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.
1.88LOEUF
pLI 0.000
Z-score -0.57
OE 1.24 (0.71–1.88)
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.
0.38Z-score
OE missense 0.93 (0.82–1.04)
196 obs / 211.7 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.1.24 (0.71–1.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.82–1.04)
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.1.09
0≤1.21.6
LoF obs/exp: 8 / 6.4Missense obs/exp: 196 / 211.7Syn Z: -0.66

ClinVar Variant Classifications

17 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS3
Benign3
8
Pathogenic
3
VUS
3
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
0
0
3
0
3
Likely Benign
0
0
0
0
0
Benign
0
0
1
2
3
Total0012214

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

View in ClinVar →

Protein Context — Lollipop Plot

P2RY6 · 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
Immunological role and clinical prognostic significance of P2RY6 in lung adenocarcinoma: a multi-omics studies and single-cell sequencing analysis.
Wu H et al.·World J Surg Oncol
2023
Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis.
Wang X et al.·Cancer Biomark
2023
Bioinformatics analysis reveals novel tumor antigens and immune subtypes of skin cutaneous melanoma contributing to mRNA vaccine development.
Yang R et al.·Front Immunol
2025
Efferocytosis-associated genes serve as prognostic biomarkers for pancreatic ductal adenocarcinoma and identify P2RY6 as a therapeutic target.
Wang X et al.·Front Immunol
2025
A prognostic model for hepatocellular carcinoma patients based on polyunsaturated fatty acid-related genes.
Lin Y et al.·Environ Toxicol
2024Cohort
The P2-receptor-mediated Ca(2+) signalosome of the human pulmonary endothelium - implications for pulmonary arterial hypertension.
Hennigs JK et al.·Purinergic Signal
2019
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
Relationship between a 7-mRNA signature of the pancreatic adenocarcinoma microenvironment and patient prognosis (a STROBE-compliant article).
He QL et al.·Medicine (Baltimore)
2020
An integrated chemokine-based machine learning model predicts prognosis and guides immunotherapy in hepatocellular carcinoma.
Zhou J et al.·Medicine (Baltimore)
2025Functional
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