Details for: P2RX3

Gene ID: 5024

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: P2RX3

Ensembl ID: ENSG00000109991

Description: purinergic receptor P2X 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pericyte CL0000669
    CSI 2.68
    rCSI 7.15%
    PRS 95.04
  • neuroplacodal cell CL0000032
    CSI 2.05
    rCSI 18.96%
    PRS 99.53

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [P2RX3](/details-gene/5024) encodes the purinergic receptor P2X 3, a member of the family of ion channels that are gated by extracellular adenosine triphosphate (ATP). Functioning as an ATP-gated non-selective cation channel, this receptor plays a crucial role in transducing signals from extracellular ATP into cellular responses, primarily through calcium influx. **Overall**, expression data highlights its significant role in specialized cell types such as the `[pericyte](/details-cell/CL0000669)` and `[neuroplacodal cell](/details-cell/CL0000032)`. Its involvement in processes like `[Behavioral response to pain](/details-go/GO:0048266)` and `[Sensory perception of taste](/details-go/GO:0050909)` underscores its importance in sensory neurobiology. Structurally, it forms homotrimers, and its gating cycle has been defined by X-ray crystallography, providing a basis for understanding its mechanism of action [Link](https://doi.org/10.1038/nature19367). ## Cellular Roles and Expression Landscape The expression profile of [P2RX3](/details-gene/5024) suggests a specialized function in a limited set of cell types. The **Overall** analysis identifies a high cell significance index (CSI) in two key populations: * **[pericyte](/details-cell/CL0000669)** (CSI: 2.68): Pericytes are mural cells that wrap around capillaries and venules, playing a critical role in the regulation of microvascular blood flow, angiogenesis, and the blood-brain barrier. The prominent expression of an ATP-gated channel in these cells suggests a mechanism for sensing local ATP, potentially released during tissue injury, inflammation, or high metabolic activity, to modulate vascular tone. * **[neuroplacodal cell](/details-cell/CL0000032)** (CSI: 2.05): These are embryonic precursor cells that give rise to various sensory neurons, including those of the cranial ganglia. High expression in this lineage is consistent with the receptor's well-established role in sensory functions, such as nociception (pain) and taste transduction, by responding to ATP released as a neurotransmitter or damage signal. The available data points to a specialized role for [P2RX3](/details-gene/5024) in vascular regulation and the development and function of the peripheral sensory nervous system. ## Pathways and Molecular Function [P2RX3](/details-gene/5024) is a key component of the purinergic signaling system, with a primary molecular function as an `[extracellularly atp-gated monoatomic cation channel activity](/details-go/GO:0004931)`. Upon binding ATP, the channel opens, leading to an influx of cations like Na+ and Ca2+. **Key Biological Processes:** * **Sensory Transduction:** The gene is strongly associated with sensory perception. It is implicated in `[Behavioral response to pain](/details-go/GO:0048266)`, `[Sensory perception of taste](/details-go/GO:0050909)`, and responses to various stimuli including `[heat](/details-go/GO:0009408)`, `[cold](/details-go/GO:0009409)`, and `[mechanical stimulus](/details-go/GO:0009612)`. This highlights its function as a primary sensor for ATP in nociceptive and gustatory neurons. * **Calcium Signaling:** As a cation channel, its activation directly contributes to the `[Elevation of cytosolic ca2+ levels](/details-pathway/R-HSA-139853)`, a central event in many signaling cascades. This is reflected in its annotation for `[Positive regulation of calcium-mediated signaling](/details-go/GO:0050850)` and `[Calcium ion transmembrane transport](/details-go/GO:0070588)`. * **Synaptic Transmission:** The receptor's role in `[Excitatory postsynaptic potential](/details-go/GO:0060079)` and `[Neuromuscular synaptic transmission](/details-go/GO:0007274)` suggests its involvement in rapid synaptic signaling in the peripheral and possibly central nervous systems, where ATP acts as a fast neurotransmitter. * **Physiological Regulation:** Its participation in processes like `[Urinary bladder smooth muscle contraction](/details-go/GO:0014832)` and `[Hemostasis](/details-pathway/R-HSA-109582)` indicates a broader role in visceral organ function and blood clotting, likely mediated by ATP signaling in smooth muscle and platelets. ## Research Directions The specific expression and function of [P2RX3](/details-gene/5024) suggest several avenues for future investigation, particularly regarding its role in physiology and pathology. **Testable Hypotheses:** 1. Given its high significance in `[pericytes](/details-cell/CL0000669)` and its function as an ATP-gated calcium channel, [P2RX3](/details-gene/5024) may mediate pericyte contraction in response to ATP released from platelets or damaged tissue, thereby regulating microvascular perfusion during injury and inflammation. 2. Based on its central role in `[Behavioral response to pain](/details-go/GO:0048266)`, selective antagonism of [P2RX3](/details-gene/5024) could be an effective strategy for treating chronic neuropathic or inflammatory pain by blocking ATP-mediated sensitization of nociceptive neurons without affecting other sensory pathways. **Proposed Experimental Approach:** To test the first hypothesis regarding the role of [P2RX3](/details-gene/5024) in pericyte-mediated microvascular control, a functional study using an *in vitro* co-culture model of human endothelial cells and primary pericytes could be employed. After allowing the cells to form capillary-like structures, the system could be stimulated with a stable ATP analog (e.g., α,β-methylene ATP). Changes in pericyte intracellular calcium levels could be monitored using a fluorescent calcium indicator like Fura-2 or GCaMP. Simultaneously, high-resolution microscopy would be used to quantify changes in the diameter of the capillary-like tubes. The experiment would be repeated in the presence of a selective P2RX3 antagonist to confirm that the observed vasoconstriction is specifically mediated by this receptor. **Therapeutic Potential:** [P2RX3](/details-gene/5024) is a highly promising therapeutic target, primarily for the treatment of chronic pain and hypersensitivity disorders. As a cell-surface ion channel expressed on peripheral sensory neurons, it is accessible to small molecule antagonists. The therapeutic strategy would be **inhibition** to block the excessive nociceptive signaling driven by extracellular ATP in chronic conditions. The detailed structural information available for the human receptor provides a strong foundation for the rational design of potent and selective inhibitors, several of which are already in clinical development for conditions like chronic cough and neuropathic pain.

Genular Protein ID: 4278112055

Symbol: P2RX3_HUMAN

Name: P2X purinoceptor 3

UniProtKB Accession Codes:

P56373 Q6DK37 Q9UQB6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 5 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 28 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 12 PDBsum 12 PIRSF 1 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 2 RefSeq 3 SMR 1 STRING 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9016352

Title: Characterization of recombinant human P2X4 receptor reveals pharmacological differences to the rat homologue.

PubMed ID: 9016352

DOI: 10.1124/mol.51.1.109

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 27626375

Title: X-ray structures define human P2X(3) receptor gating cycle and antagonist action.

PubMed ID: 27626375

DOI: 10.1038/nature19367

Sequence Information:

  • Length: 397
  • Mass: 44289
  • Checksum: 3CB0081E65748EED
  • Sequence:
    • MNCISDFFTY ETTKSVVVKS WTIGIINRVV QLLIISYFVG WVFLHEKAYQ VRDTAIESSV 
VTKVKGSGLY ANRVMDVSDY VTPPQGTSVF VIITKMIVTE NQMQGFCPES EEKYRCVSDS 
QCGPERLPGG GILTGRCVNY SSVLRTCEIQ GWCPTEVDTV ETPIMMEAEN FTIFIKNSIR 
FPLFNFEKGN LLPNLTARDM KTCRFHPDKD PFCPILRVGD VVKFAGQDFA KLARTGGVLG 
IKIGWVCDLD KAWDQCIPKY SFTRLDSVSE KSSVSPGYNF RFAKYYKMEN GSEYRTLLKA 
FGIRFDVLVY GNAGKFNIIP TIISSVAAFT SVGVGTVLCD IILLNFLKGA DQYKAKKFEE 
VNETTLKIAA LTNPVYPSDQ TTAEKQSTDS GAFSIGH