P2RX7

protein-coding

purinergic receptor P2X 7, the group of Purinergic receptors P2X

Gene summary

The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel and is responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Activation of this nuclear receptor by ATP in the cytoplasm may be a mechanism by which cellular activity can be coupled to changes in gene expression. Multiple alternatively spliced variants have been identified, most of which fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2010]

MANE transcript

NM_002562.6

Inheritance

—

ClinVar variants

U:73B:14

Top phenotype

P2RX7-related disorder

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr12:121,132,819-121,188,032

External References & Databases

Ensembl (ENSG00000089041)

Transcript & Mutation Effects

hg38 • Region Span ~55.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to P2RX7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 11

P2RX7-related disorderTotal: 2

Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002562.6. 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			2 clinvar	2 clinvar	1 clinvar	5
missense			68 clinvar	6 clinvar	4 clinvar	78
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar	1 clinvar		4
Total	0	0	73	9	5	87

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_002562.6	RefSeq	NP_002553.3	13	MANE Select
ENST00000328963.10	Ensembl	ENSP00000330696.6	13	MANE Select
ENST00000261826.10	Ensembl	ENSP00000261826.6	5	Standard
ENST00000535250.5	Ensembl	ENSP00000442572.2	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
p2rx7	Danio rerio	Structure: macrophage chemotaxis Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

p2rx7

Danio rerio

Structure: macrophage chemotaxis

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Calcium signaling pathway - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
The NLRP3 inflammasome
Inflammasomes

Biological Process

activation of MAPK activity
cell morphogenesis
phagolysosome assembly
positive regulation of T cell mediated cytotoxicity
regulation of sodium ion transport

Molecular Function

lipopolysaccharide binding
purinergic nucleotide receptor activity
extracellularly ATP-gated cation channel activity
signaling receptor binding
protein binding

Cellular Component

integral component of nuclear inner membrane
cytoplasm
plasma membrane
integral component of plasma membrane
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000546057
Coding exons: 13
Length: 53255
Individuals with no LoFs: 124173
Homozygous LoFs: 9
Heterozygous LoFs: 1566
Defined: 125748
p: 0.00628

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.401	327	348	0.939	0.0000198	3902
Missense (PolyPhen)		114	121.67	0.937		1419
Synonymous	0.553	130	138	0.940	0.00000831	1091
Loss of Function	1.95	22	34.3	0.641	0.00000191	369

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0020	0.0020	notable
Latino/Admixed American	0.0053	0.0053	notable
Ashkenazi Jewish	0.0079	0.0080	notable
East Asian	0.0048	0.0047	notable
Finnish	0.0025	0.0025	notable
European (Non-Finnish)	0.0091	0.0090	notable
South Asian	0.0018	0.0018	notable
Other	0.0098	0.0098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for ATP that acts as a ligand-gated ion channel. Responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells. In the absence of its natural ligand, ATP, functions as a scavenger receptor in the recognition and engulfment of apoptotic cells (PubMed:21821797, PubMed:23303206). {ECO:0000269|PubMed:21821797, ECO:0000269|PubMed:23303206, ECO:0000269|PubMed:28326637}.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.966
RVIS EVS: 2.83
RVIS percentile EVS: 99.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.250

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High