P2RX1

Chr 17

purinergic receptor P2X 1

Also known as: P2X1

NCBI Gene: 5023 ENSG00000108405 UniProt: P51575 OMIM: 600845

P2RX1 encodes an ATP-gated cation channel that mediates rapid synaptic transmission in smooth muscle and contributes to platelet activation, neutrophil chemotaxis, and smooth muscle contractions in the vas deferens and urinary bladder. Mutations cause autosomal recessive episodic bleeding due to platelet dysfunction. The gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the P2X family of G-protein-coupled receptors. These proteins can form homo-and heterotimers and function as ATP-gated ion channels and mediate rapid and selective permeability to cations. This protein is primarily localized to smooth muscle where binds ATP and mediates synaptic transmission between neurons and from neurons to smooth muscle and may being responsible for sympathetic vasoconstriction in small arteries, arterioles and vas deferens. Mouse studies suggest that this receptor is essential for normal male reproductive function. This protein may also be involved in promoting apoptosis. [provided by RefSeq, Jun 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.21

Clinical Summary— P2RX1

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Gene-Disease Validity (ClinGen)

inherited bleeding disorder, platelet-type · ADDisputed

Disputed — evidence questions this relationship

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

57 VUS of 94 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.000

Z-score 0.81

OE 0.81 (0.56–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.02Z-score

OE missense 0.81 (0.72–0.92)

197 obs / 241.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.81 (0.56–1.21)

0≤0.351.4

Missense OE?0.81 (0.72–0.92)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 18 / 22.1Missense obs/exp: 197 / 241.7Syn Z: 0.14

This gene — mechanism propensity

0.6453th %ile

GOF

0.6737th %ile

LOF

0.2680th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

VUS57

Likely Benign13

Benign16

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	57	0	0	57
Likely Benign	3	4	6	13
Benign	1	13	2	16
Total	61	17	8	86

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 43) ClinVar copy-number / structural variants overlap P2RX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →