P2RX6
protein-codingpurinergic receptor P2X 6, the group of Purinergic receptors P2X
Gene summary
The protein encoded by this gene belongs to the family of P2X receptors, which are ATP-gated ion channels and mediate rapid and selective permeability to cations. This gene is predominantly expressed in skeletal muscle, and regulated by p53. The encoded protein is associated with VE-cadherin at the adherens junctions of human umbilical vein endothelial cells. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 22, has been identified. [provided by RefSeq, Apr 2009]
- P2RXL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005336
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to P2RX6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005446.5. 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 | 62 | 7 | 69 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 64 | 7 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005437.2 | 12 | MANE Select | |
| Ensembl | ENSP00000416193.2 | 12 | MANE Select | |
| RefSeq | NP_001153026.1 | 12 | Standard | |
| RefSeq | NP_001336803.1 | 9 | Standard |
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)
- Hemostasis
- Elevation of cytosolic Ca2+ levels
- Platelet calcium homeostasis
Biological Process
- cation transport
- muscle contraction
- signal transduction
- blood coagulation
- response to ATP
Molecular Function
- purinergic nucleotide receptor activity
- transmembrane signaling receptor activity
- extracellularly ATP-gated cation channel activity
- ATP binding
- channel activity
Cellular Component
- integral component of nuclear inner membrane
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- postsynaptic density
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000413302
- Coding exons
- 12
- Length
- 19023
- Individuals with no LoFs
- 125372
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 221
- Defined
- 125593
- p
- 0.000880
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.840 | 212 | 249 | 0.850 | 0.0000148 | 2789 |
| Missense (PolyPhen) | 83 | 90.942 | 0.91267 | 1175 | ||
| Synonymous | -0.184 | 110 | 108 | 1.02 | 0.00000720 | 849 |
| Loss of Function | 1.20 | 16 | 22.1 | 0.724 | 0.00000104 | 244 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00056 | 0.00055 | rare |
| Latino/Admixed American | 0.00096 | 0.00095 | rare |
| Ashkenazi Jewish | 0.0037 | 0.0036 | notable |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00099 | 0.00099 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for ATP that acts as a ligand-gated ion channel. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.987
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 40.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.971
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |