P2RX6

Chr 22

purinergic receptor P2X 6

Also known as: P2RXL1, P2X6, P2XM

NCBI Gene: 9127ENSG00000099957UniProt: O15547OMIM: 608077

The P2RX6 protein functions as a modulatory subunit of ATP-gated ion channels, requiring P2RX4 or P2RX2 for plasma membrane localization and forming functional heterotrimeric receptors, and can translocate to the nucleus to regulate post-transcriptional modifications in neurons. This gene is not highly constrained against loss-of-function variants and currently has no established disease associations in humans. Clinical significance of P2RX6 variants remains to be determined.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.10
Clinical Summary— P2RX6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
350 unique Pathogenic / Likely Pathogenic· 118 VUS of 486 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.20
OE 0.72 (0.49–1.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.84Z-score
OE missense 0.85 (0.76–0.95)
212 obs / 249.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.49–1.10)
0≤0.351.4
Missense OE0.85 (0.76–0.95)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 16 / 22.1Missense obs/exp: 212 / 249.3Syn Z: -0.18
DN
0.6937th %ile
GOF
0.75top 25%
LOF
0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

486 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic317
Likely Pathogenic33
VUS118
Likely Benign8
Benign2
Conflicting2
317
Pathogenic
33
Likely Pathogenic
118
VUS
8
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
317
0
317
Likely Pathogenic
0
0
33
0
33
VUS
1
60
57
0
118
Likely Benign
0
7
1
0
8
Benign
0
0
2
0
2
Conflicting
—2
Total1674100480

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

P2RX6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
[An epigenetic clock model for assessing the human biological age of healthy aging].
Ni XL et al.·Zhonghua Yi Xue Za Zhi
2022Functional
Detection of Selection Signatures in Anqing Six-End-White Pigs Based on Resequencing Data
Chen Y et al.·Genes (Basel)
2022
Comparative Transcriptome Profiling of Ileal and Cecal Tissues Between Pekin Ducks and Shaoxing Ducks.
Wang D et al.·Genes (Basel)
2025
RNA-seq reveals that anti-obesity irisin and triiodothyronine (T3) hormones differentially affect the purinergic signaling transcriptomics in differentiated human adipocytes.
Mathias LS et al.·Biochim Biophys Acta Mol Cell Biol Lipids
2023
Expansion of Schizophrenia Gene Network Knowledge Using Machine Learning Selected Signals From Dorsolateral Prefrontal Cortex and Amygdala RNA-seq Data
Liu Y et al.·Front Psychiatry
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients