P2RY6

Chr 11

pyrimidinergic receptor P2Y6

Also known as: P2Y6

NCBI Gene: 5031 ENSG00000171631 UniProt: Q15077

The P2RY6 protein is a G-protein coupled receptor that binds extracellular UDP and mediates inflammatory responses through phosphatidylinositol-calcium signaling. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, presenting in infancy with severe intellectual disability, seizures, and progressive brain atrophy. This gene is not highly constrained against loss-of-function variants in the general population.

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, 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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

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?

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?

0.38Z-score

OE missense 0.93 (0.82–1.04)

196 obs / 211.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.24 (0.71–1.88)

0≤0.351.4

Missense OE?0.93 (0.82–1.04)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 8 / 6.4Missense obs/exp: 196 / 211.7Syn Z: -0.66

Background carrier burden — how many people carry a rare variant somewhere in P2RY6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

434 rare PASS variants

Rare truncating (LoF)

1 in 2,500

72 rare PASS variants

Rare synonymous (reference)

1 in 180

199 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for P2RY6. 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 120	1 in 2,500
South Asian	~43k	1 in 89	1 in 1,800
Remaining (unassigned)	~30k	1 in 81	1 in 5,000
European (Finnish)	~27k	1 in 320	1 in 1,700
Admixed American	~22k	1 in 98	1 in 2,800
African / African American	~21k	1 in 110	1 in 2,200
East Asian	~20k	1 in 97	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 97	1 in 580

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 ↓