P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7)
2008-01-01 Pablo Pelegrin , Annmarie Surprenant AffiliationFaculty of Life Science, Michael Smith Building, University of Manchester, Manchester, M13 9PT, UK
DNA/RNA
Description
The P2RX7 gene is comprised of 13 coding exons.
Transcription
The full length transcript is 3135 bp long and 10 alternative splicing isoforms have been identified.
Pseudogene
Not known.
Proteins
Description
The protein has 595 residues amino acids and compromises a 69 kDa calculated molecular weight. However, N-glycosylation in the extracellular loop increases the size of the P2X7 receptor to about 75-85 KDa; the protein is composed successively (from the N- to the C-terminus) by:
25 amino acid intracellular N-terminus
21 amino acid first transmembrane domain
288 amino acid extracellular loop
21 amino acid second transmembrane domain
240 amino acid intracellular C-terminal region
Expression
In a wide variety of tissues including heart, liver, pancreas, thymus, skeletal muscle and brain, although in brain the expression is mainly restricted to microglia. It also has relevant expression and function in immune cells (mainly in antigen presenting cells, such as monocytes, macrophages and dendritic cells).
Localisation
Mainly is found in the plasma membrane, however it also can be found in intracellular membrane compartments while trafficking to the plasma membrane.
Function
Acts as a ligand gated ion channel, sensing high concentration of extracellular ATP. Responsible for ATP-dependent activation and release of proinflammatory cytokines of the interleukin-1 family, mainly interleukin-1beta, interleukin-18 and interleukin-1alpha, playing a pivotal role in inflammatory responses. Prolonged stimulation of the P2X7 receptor can lead to plasma membrane bleb formation, opening of pannexin-1 dependent membrane pores and eventual cell death.
Homology
With other P2X receptors, with the higher homology with P2RX4. Excluding the unique C-terminal domain, homology is 39-49% with other P2X receptors.
Mutations
Germinal
The human P2X7 receptor gene is highly polymorphic and more then 260 SNP have been described, only four loss-of-function and one gain-of-function SNP have been described to date:
Loss of protein function:
946 G to A (Arg-307 to Gln)
1068 G to A (Ala-348 to Thr)
1513 A to C (Glu-496 to Ala)
1729 T to A (Ile-568 to Asp)
Gain of protein function:
489 C to T (His-155 to Tyr)
1068 G to A (Ala-348 to Thr)
1513 A to C (Glu-496 to Ala)
1729 T to A (Ile-568 to Asp)
Somatic
Not known in human.
Implicated in
Entity name
Extrapulmonary tuberculosis
Note
The P2RX7 1513C allele has been strongly associated with extrapulmonary tuberculosis. The allele was associated with a reduced killing of Mycobacterium tuberculosis by macrophages.
Entity name
Chronic lymphoid leukemia (CLL)
Note
The 1513C allele of P2RX7 has been associated with the clinical course of patients affected by chronic lymphocytic leukemia (CLL).
There is a possible role for the P2X7 receptor in the susceptibility to familial CLL or, alternately, the 1513C allele may be in linkage disequilibrium with a nearby susceptibility gene.
There is a possible role for the P2X7 receptor in the susceptibility to familial CLL or, alternately, the 1513C allele may be in linkage disequilibrium with a nearby susceptibility gene.
Entity name
Various cancers, including breast cancer, prostate cancer, papillary thyroid cancer and neuroblastoma.
Note
P2X7 receptor is overexpressed in a variety of cancers (see above). A detailed understanding of the mechanistic contribution mediated by P2RX7 has yet to be established. However, there is substantial evidence that the P2X7 receptor may mediate cell survival and growth by increasing the efficiency of oxidative phosphorylation and total intracellular ATP stores. Finally it has been proposed that the P2X7 receptor may be a candidate marker of papillary thyroid cancer.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15901833 | 2005 | Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. | Adinolfi E et al |
| 15972634 | 2005 | A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. | Cabrini G et al |
| 15896293 | 2005 | Identification and characterization of splice variants of the human P2X7 ATP channel. | Cheewatrakoolpong B et al |
| 15180873 | 2004 | Association of the 1513C polymorphism in the P2X7 gene with familial forms of chronic lymphocytic leukaemia. | Dao-Ung LP et al |
| 16624800 | 2006 | A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization. | Feng YH et al |
| 17095747 | 2007 | A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis. | Fernando SL et al |
| 16547218 | 2006 | The P2X7 receptor: a key player in IL-1 processing and release. | Ferrari D et al |
| 15123679 | 2004 | An Arg307 to Gln polymorphism within the ATP-binding site causes loss of function of the human P2X7 receptor. | Gu BJ et al |
| 11150303 | 2001 | A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. | Gu BJ et al |
| 12270951 | 2002 | Molecular physiology of P2X receptors. | North RA et al |
| 17036048 | 2006 | Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. | Pelegrin P et al |
| 16424024 | 2006 | The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism. | Raffaghello L et al |
| 9038151 | 1997 | The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA. | Rassendren F et al |
| 14997049 | 2004 | Differentiation between cancerous and normal hyperplastic lobules in breast lesions. | Slater M et al |
| 17947359 | 2008 | Increased P2X7 receptor expression and function in thyroid papillary cancer: a new potential marker of the disease? | Solini A et al |
| 8614837 | 1996 | The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). | Surprenant A et al |
| 12586825 | 2003 | An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor. | Wiley JS et al |
Other Information
Locus ID:
NCBI: 5027
MIM: 602566
HGNC: 8537
Ensembl: ENSG00000089041
Variants:
dbSNP: 5027
ClinVar: 5027
TCGA: ENSG00000089041
COSMIC: P2RX7
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA445210 | Pain, Postoperative | Disease | ClinicalAnnotation | associated | PD | ||
| PA449599 | fentanyl | Chemical | ClinicalAnnotation | associated | PD |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37067746 | 2024 | The P2X7 receptor in mucosal adaptive immunity. | 1 |
| 37742908 | 2024 | Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions. | 2 |
| 38255938 | 2024 | Embers of the Past: Early Childhood Traumas Interact with Variation in P2RX7 Gene Implicated in Neuroinflammation on Markers of Current Suicide Risk. | 1 |
| 38339008 | 2024 | P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33. | 0 |
| 38401466 | 2024 | P2RX7 gene variants associate with altered inflammasome assembly and reduced pyroptosis in chronic nonbacterial osteomyelitis (CNO). | 0 |
| 38473744 | 2024 | P2X7 Receptor in Dendritic Cells and Macrophages: Implications in Antigen Presentation and T Lymphocyte Activation. | 0 |
| 38508051 | 2024 | The impact of the P2X7 receptor on the tumor immune microenvironment and its effects on tumor progression. | 0 |
| 38870128 | 2024 | Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells. | 0 |
| 38892324 | 2024 | Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection. | 0 |
| 38993566 | 2024 | P2X7R Modulates NEK7-NLRP3 Interaction to Exacerbate Experimental Autoimmune Prostatitis via GSDMD-mediated Prostate Epithelial Cell Pyroptosis. | 0 |
| 37067746 | 2024 | The P2X7 receptor in mucosal adaptive immunity. | 1 |
| 37742908 | 2024 | Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions. | 2 |
| 38255938 | 2024 | Embers of the Past: Early Childhood Traumas Interact with Variation in P2RX7 Gene Implicated in Neuroinflammation on Markers of Current Suicide Risk. | 1 |
| 38339008 | 2024 | P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33. | 0 |
| 38401466 | 2024 | P2RX7 gene variants associate with altered inflammasome assembly and reduced pyroptosis in chronic nonbacterial osteomyelitis (CNO). | 0 |
Citation
Pablo Pelegrin ; Annmarie Surprenant
P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7)
Atlas Genet Cytogenet Oncol Haematol. 2008-01-01
Online version: http://atlasgeneticsoncology.org/gene/41623/p2rx7-(purinergic-receptor-p2x-ligand-gated-ion-channel-7)
