P2RX4: The Purinergic P2X4 Receptor Gene
A key mediator of ATP signaling in immune, neuronal, and vascular systems, implicated in neuropathic pain, inflammation, and cardiovascular physiology.
Gene Information Card
| Symbol | P2RX4 |
|---|---|
| Full Name | Purinergic Receptor P2X 4 |
| Gene Type | protein coding |
| Chromosomal Location | 12q24.31 |
| NCBI Gene ID | 5025 ncbi.nlm.nih.gov/gene/5025 |
| Ensembl ID | ENSG00000135124 |
| UniProt ID | Q99571 |
| OMIM ID | 600465 |
| HGNC ID | 15494 |
| Aliases | P2X4, P2X4R, P2X purinoceptor 4 |
Description
The P2RX4 gene encodes the P2X4 receptor, a ligand-gated ion channel activated by extracellular ATP. This receptor is a trimeric complex that forms a non-selective cation channel permeable to Na+, K+, and Ca2+. P2X4 is widely expressed across tissues, with prominent roles in immune cells (particularly microglia and macrophages), neurons, and vascular endothelium. Its activation triggers calcium influx, leading to various downstream signaling cascades. P2RX4 is critically involved in neuropathic pain, neuroinflammation, and cardiovascular regulation. It is also a target for therapeutic intervention in chronic pain and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Neuropathic Pain | Upregulation of P2RX4 in spinal cord microglia following nerve injury; activation leads to release of brain-derived neurotrophic factor (BDNF), which alters neuronal chloride homeostasis and enhances pain signaling. | NCBI Gene, OMIM, PubMed (Tsuda et al., 2003) |
| Chronic Inflammatory Conditions | P2RX4 activation in macrophages promotes NLRP3 inflammasome activation and IL-1β release, contributing to inflammation in conditions like rheumatoid arthritis and inflammatory bowel disease. | NCBI Gene, PubMed |
| Cardiovascular Disease | P2RX4 is expressed in vascular endothelium and cardiac myocytes; its activation influences vascular tone, endothelial function, and cardiac remodeling, with implications in hypertension and heart failure. | NCBI Gene, PubMed |
| Pulmonary Hypertension | P2RX4 expression is altered in pulmonary artery smooth muscle cells, contributing to vascular remodeling and increased pulmonary arterial pressure. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Lung | 24.5 | Medium |
| Spleen | 22.1 | Medium |
| Bone Marrow | 18.7 | Medium |
| Brain | 12.3 | Low |
| Heart | 10.2 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| THP-1 (Monocyte) | 35.2 | High expression; key in immune response |
| HUVEC (Endothelial) | 28.4 | Important for vascular function |
| SH-SY5Y (Neuroblastoma) | 15.6 | Moderate expression; used in neuronal studies |
| A549 (Lung Carcinoma) | 12.8 | Moderate expression |
| HeLa (Cervical Carcinoma) | 8.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| rs25644 (Tyr315Cys) | Missense | ~5% in European populations | Alters receptor desensitization and ATP sensitivity; may affect pain sensitivity. |
| rs28385397 (Ala87Val) | Missense | ~2% in global populations | Potential impact on receptor trafficking and surface expression. |
| rs2296051 (Intronic) | Intronic | ~30% in global populations | Associated with altered P2RX4 expression levels in some studies; clinical significance unclear. |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations in P2RX4 are rare and often lethal in animal models. In humans, partial loss-of-function variants may reduce ATP-induced calcium influx, potentially impairing immune responses and increasing susceptibility to infections.
Gain of Function (GOF)
Gain-of-function mutations, such as some variants in the transmembrane domain, can lead to increased channel activity, prolonged opening, and enhanced calcium influx. This can result in exacerbated neuroinflammation and chronic pain states.
Dominant Negative (DN)
Dominant-negative effects have been proposed for certain missense mutations that disrupt the trimeric assembly of the receptor, leading to reduced functional channels on the cell surface. This mechanism is hypothesized to contribute to altered pain signaling.
View complete mutation data：
Gene Ontology (GO)
| • extracellular ATP-gated monoatomic cation channel activity | • purinergic nucleotide receptor activity |
| • calcium ion transmembrane transporter activity | • protein homotrimerization activity |
| • plasma membrane | • integral component of plasma membrane |
| • response to ATP | • calcium ion transmembrane transport |
| • cation transport | • signal transduction |
| • immune response | • neuroinflammatory response |
Pathways
• Purinergic signaling
• ATP-gated ion channel signaling
• Microglia-mediated neuroinflammation
• NLRP3 inflammasome pathway
• Calcium signaling pathway
Protein Summary
The P2X4 protein is a 388-amino acid polypeptide that forms a homotrimeric ATP-gated ion channel. Each subunit has two transmembrane domains (TM1 and TM2), a large extracellular loop containing the ATP-binding site, and intracellular N- and C-termini. The channel is permeable to Na+, K+, and Ca2+. Upon ATP binding, the channel opens, allowing cation influx, which depolarizes the membrane and triggers intracellular signaling cascades. P2X4 is characterized by rapid desensitization and is modulated by various factors, including zinc, ivermectin, and extracellular pH. It plays a critical role in microglial signaling, synaptic plasticity, and inflammatory responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| P2RX4 Knockout HEK293 Cell Line | EDJ-KQ1573 | Human | 5025 | Details Get a Quote |
| P2RX4 Knockout A-549 Cell Line | EDJ-KQ19900 | Human | 5025 | Details Get a Quote |
| P2RX4 Knockout HCT 116 Cell Line | EDJ-KQ21257 | Human | 5025 | Details Get a Quote |
| P2RX4 Knockout HeLa Cell Line | EDJ-KQ21258 | Human | 5025 | Details Get a Quote |
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