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9 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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P2RX6
purinergic receptor P2X 6
Chromosome 22 · 22q11.21
NCBI Gene: 9127Ensembl: ENSG00000099957.18HGNC: HGNC:8538UniProt: O15547
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytoplasmcell junctionsignaling receptor complexextracellularly ATP-gated monoatomic cation channel activityagingdepressive disorderhepatocellular carcinomacancer
✦AI Summary

P2RX6 is a purinergic ATP receptor that functions primarily as a modulatory subunit rather than an independent channel. Unlike other P2X receptor family members, P2RX6 cannot form functional homotrimers and requires heterodimerization with P2RX4 or P2RX2 to reach the plasma membrane and establish functional heterotrimeric receptors 1. Beyond membrane localization, P2RX6 translocates to the nucleus where it regulates post-transcriptional modifications in neurons. In renal cell carcinoma, the ATP-P2RX6 axis activates Ca²⁺-mediated p-ERK1/2/MMP9 signaling to promote cell migration and invasion, contributing to metastasis 2. P2RX6 expression decreases with age in subcutaneous adipose tissue and responds to thyroid hormone signaling, suggesting involvement in age-related metabolic dysfunction and mitochondrial changes 3. At the genetic level, P2RX6 methylation serves as a biomarker in epigenetic aging models, with methylation levels changing significantly across the lifespan 4. In schizophrenia, P2RX6 emerged as part of neuroactive ligand-receptor interaction pathways through machine learning analysis of brain transcriptomics 5. Additionally, P2RX6 is implicated in reward circuitry and substance dependence susceptibility 6, and its expression in adipocytes is differentially regulated by anti-obesity hormones including thyroid hormone and irisin 7.

Sources cited
1
P2RX6 does not form functional homotrimers and requires P2RX4 or P2RX2 for plasma membrane trafficking and heterotrimeric receptor formation
PMID: 22378790
2
ATP-P2RX6 signaling activates Ca²⁺-mediated p-ERK1/2/MMP9 pathway to promote renal cell carcinoma migration, invasion, and metastasis
PMID: 31159832
3
P2RX6 expression decreases with age in subcutaneous adipose tissue and is regulated by thyroid hormone signaling in age-related metabolic dysfunction
PMID: 37626392
4
P2RX6 methylation at cg05442902 locus serves as biomarker in epigenetic clock model for biological age assessment
PMID: 35012300
5
P2RX6 is differentially expressed in schizophrenia brain and participates in neuroactive ligand-receptor interaction pathways
PMID: 35386517
6
P2RX6 genetic variants associate with alcohol and drug dependence liability and reward-related ventral striatum activation
PMID: 31099175
7
P2RX6 expression in human adipocytes is differentially regulated by thyroid hormone T3 and irisin during browning and thermogenesis
PMID: 36642213
Disease Associationsⓘ20
agingOpen Targets
0.22Weak
depressive disorderOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
cancerOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
lung cancerOpen Targets
0.03Suggestive
migraine disorderOpen Targets
0.03Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
colitisOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
hypertensionOpen Targets
0.02Suggestive
asthmaOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
HIV-1 infectionOpen Targets
0.02Suggestive
glaucomaOpen Targets
0.02Suggestive
Parkinson diseaseOpen Targets
0.02Suggestive
Toriello-Lacassie-Droste syndromeOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
gastric cancerOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GRIN1Protein interaction97%GRIN2AProtein interaction97%GRIN2CProtein interaction97%GRIN2DProtein interaction97%P2RY2Protein interaction97%P2RY4Protein interaction97%
Tissue Expression6 tissues
Brain
100%
Heart
90%
Lung
47%
Ovary
46%
Liver
29%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
P2RX6GRIN1GRIN2AGRIN2CGRIN2DP2RY2P2RY4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O15547
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.53LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.24 [1.01–1.53]
RankingsWhere P2RX6 stands among ~20K protein-coding genes
  • #12,407of 20,598
    Most Researched28
  • #15,357of 17,882
    Most Constrained (LOEUF)1.53
Genes detectedP2RX6
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
Subcutaneous adipose tissue alteration in aging process associated with thyroid hormone signaling.
PMID: 37626392
BMC Med Genomics · 2023
1.00
2
[An epigenetic clock model for assessing the human biological age of healthy aging].
PMID: 35012300
Zhonghua Yi Xue Za Zhi · 2022
0.89
3
The m
PMID: 31159832
J Exp Clin Cancer Res · 2019
0.78
4
Prioritizing Genetic Contributors to Cortical Alterations in 22q11.2 Deletion Syndrome Using Imaging Transcriptomics.
PMID: 33638978
Cereb Cortex · 2021
0.67
5
miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels.
PMID: 28614186
Pain · 2017
0.56