P2RX1

protein-coding

purinergic receptor P2X 1, the group of Purinergic receptors P2X

Gene summary

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]

MANE transcript

NM_002558.4

Inheritance

ClinVar variants

U:59B:13

Top phenotype

P2RX1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr17:3,896,592-3,916,476

External References & Databases

Ensembl (ENSG00000108405)

Transcript & Mutation Effects

hg38 • Region Span ~19.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inherited bleeding disorder, platelet-typeNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0000009

Submitter: ClinGen

The P2RX1 gene was first associated with platelet dysfunction in 2000 by Oury et al. (PMID: 10816552), who reported a somatic heterozygous 3-bp deletion (p.Leu351del) in a child with severe mucocutaneous bleeding and selective impairment of ADP-induced platelet aggregation; this variant was later shown to be incompatible with P2X1 biology as an ATP-gated ion channel rather than an ADP receptor, leading to its reclassification as a VUS by OMIM. A second case was shared via internal ClinGen Hemostasis/Thrombosis GCEP communication by Dr. Marie-Christine Kopp in April 2026, describing a patient with non-syndromic inherited platelet function disorder carrying a heterozygous nonsense variant (c.100C>T; p.Arg34Ter), normal platelet count and size, and selective aggregation defects to ADP, collagen, and epinephrine. Despite these two reports, genetic evidence remains limited and biologically inconsistent with known P2X1 function, while experimental data from mouse models support a role in high-shear thrombosis but not in a matching human bleeding phenotype. In summary, there is disputed evidence to support a gene-disease relationship between P2RX1 and platelet dysfunction, and this classification was determined following review by the ClinGen Hemostasis/Thrombosis GCEP.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to P2RX1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 54

P2RX1-related disorderTotal: 22

not providedTotal: 4

Platelet-type bleeding disorder 8Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002558.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar	2 clinvar	9
missense			58 clinvar	4 clinvar	1 clinvar	63
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	59	10	3	72

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002558.4	RefSeq	NP_002549.1	12	MANE Select
ENST00000225538.4	Ensembl	ENSP00000225538.3	12	MANE Select
ENST00000571637.1	Ensembl	ENSP00000460449.1	2	Standard
ENST00000861554.1	Ensembl	ENSP00000531613.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Platelet activation - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Platelet Aggregation Inhibitor Pathway, Pharmacodynamics
Neutrophil degranulation

Biological Process

serotonin secretion by platelet
regulation of vascular smooth muscle contraction
ion transport
cation transport
apoptotic process

Molecular Function

purinergic nucleotide receptor activity
extracellularly ATP-gated cation channel activity
cation channel activity
ATP binding
zinc ion binding

Cellular Component

integral component of nuclear inner membrane
plasma membrane
integral component of plasma membrane
external side of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000225538
Coding exons: 12
Length: 19909
Individuals with no LoFs: 125643
Homozygous LoFs: 0
Heterozygous LoFs: 105
Defined: 125748
p: 0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	197	242	0.815	0.0000158	2626
Missense (PolyPhen)		72	107.13	0.67206		1256
Synonymous	0.135	96	97.7	0.983	0.00000678	768
Loss of Function	0.813	18	22.1	0.813	0.00000114	241

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.0015	0.0015	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00050	0.00049	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00082	0.00082	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ligand-gated ion channel with relatively high calcium permeability. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Seems to be linked to apoptosis, by increasing the intracellular concentration of calcium in the presence of ATP, leading to programmed cell death (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.171

Intolerance Scores

LoFtool: 0.872
RVIS EVS: -0.49
RVIS percentile EVS: 22.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.157

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium