P2RX3
protein-codingpurinergic receptor P2X 3, the group of Purinergic receptors P2X
Gene summary
This gene encodes a member of the P2X purinergic receptor (purinoceptor) gene family which includes seven members (P2RX1 - P2RX7). P2X purinoceptors are a family of cation-permeable, ligand-gated ion channels that open in response to the binding of extracellular adenosine 5'-triphosphate (ATP). The encoded protein is a subunit of the trimeric P2X3 receptor ion channel which is expressed by sensory or autonomic neurons. A deficiency of the orthologous protein in mice is associated with reduced pain-related behavior and urinary bladder hyporeflexia. [provided by RefSeq, Aug 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.0 kbGenCC 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 P2RX3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002559.5. 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 | 0 | |||||
| missense | 67 | 2 | 1 | 70 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 67 | 3 | 1 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002550.2 | 12 | MANE Select | |
| Ensembl | ENSP00000263314.2 | 12 | MANE Select | |
| Ensembl | ENSP00000434166.1 | 2 | Standard | |
| Ensembl | ENSP00000562468.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| p2rx3a | Danio rerio | Structure: pharyngeal arch 1 Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Calcium signaling pathway - Homo sapiens (human)
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- Taste transduction - Homo sapiens (human)
- Hemostasis
- Elevation of cytosolic Ca2+ levels
Biological Process
- response to hypoxia
- cation transport
- signal transduction
- neuromuscular synaptic transmission
- blood coagulation
Molecular Function
- purinergic nucleotide receptor activity
- extracellularly ATP-gated cation channel activity
- ATP binding
- ATP-gated ion channel activity
Cellular Component
- integral component of nuclear inner membrane
- rough endoplasmic reticulum
- Golgi apparatus
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263314
- Coding exons
- 12
- Length
- 32226
- Individuals with no LoFs
- 125604
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 143
- Defined
- 125748
- p
- 0.000573
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.27 | 186 | 242 | 0.770 | 0.0000141 | 2600 |
| Missense (PolyPhen) | 79 | 112.23 | 0.70394 | 1223 | ||
| Synonymous | 0.342 | 90 | 94.2 | 0.955 | 0.00000619 | 733 |
| Loss of Function | 1.81 | 13 | 22.2 | 0.586 | 0.00000103 | 256 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0057 | 0.0056 | notable |
| Latino/Admixed American | 0.00067 | 0.00067 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00046 | 0.00046 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for ATP that acts as a ligand-gated cation channel (PubMed:27626375). Plays a role in sensory perception. Required for normal perception of pain. Required for normal taste perception (By similarity). {ECO:0000250|UniProtKB:Q3UR32, ECO:0000269|PubMed:27626375}.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.700
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.148
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |