Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1FNTXA)

DOT Name P2X purinoceptor 6 (P2RX6)
Synonyms P2X6; ATP receptor; P2XM; Purinergic receptor; Purinergic receptor P2X-like 1
Gene Name P2RX6
Related Disease
Autosomal recessive polycystic kidney disease ( )
Mood disorder ( )
Pulmonary disease ( )
Advanced cancer ( )
Alzheimer disease ( )
Arrhythmia ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Brain neoplasm ( )
Bronchopulmonary dysplasia ( )
Carcinoma ( )
Cardiac failure ( )
Congestive heart failure ( )
Cystic fibrosis ( )
Dengue ( )
Depression ( )
Eosinophilic esophagitis ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Hyperglycemia ( )
Influenza ( )
Lung cancer ( )
Lung carcinoma ( )
Major depressive disorder ( )
Malignant soft tissue neoplasm ( )
Multiple sclerosis ( )
Myeloid leukaemia ( )
Narcolepsy ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Parkinson disease ( )
Pulmonary fibrosis ( )
Rheumatoid arthritis ( )
Sarcoma ( )
Schizophrenia ( )
Status epilepticus seizure ( )
Systemic lupus erythematosus ( )
Vascular disease ( )
Benign neoplasm ( )
Chronic obstructive pulmonary disease ( )
Amyotrophic lateral sclerosis ( )
Bipolar disorder ( )
Hepatitis ( )
Neuralgia ( )
Neuroblastoma ( )
Periodontitis ( )
UniProt ID
P2RX6_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00864
Sequence
MCPQLAGAGSMGSPGATTGWGLLDYKTEKYVMTRNWRVGALQRLLQFGIVVYVVGWALLA
KKGYQERDLEPQFSIITKLKGVSVTQIKELGNRLWDVADFVKPPQGENVFFLVTNFLVTP
AQVQGRCPEHPSVPLANCWVDEDCPEGEGGTHSHGVKTGQCVVFNGTHRTCEIWSWCPVE
SGVVPSRPLLAQAQNFTLFIKNTVTFSKFNFSKSNALETWDPTYFKHCRYEPQFSPYCPV
FRIGDLVAKAGGTFEDLALLGGSVGIRVHWDCDLDTGDSGCWPHYSFQLQEKSYNFRTAT
HWWEQPGVEARTLLKLYGIRFDILVTGQAGKFGLIPTAVTLGTGAAWLGVVTFFCDLLLL
YVDREAHFYWRTKYEEAKAPKATANSVWRELALASQARLAECLRRSSAPAPTATAAGSQT
QTPGWPCPSSDTHLPTHSGSL
Function Receptor for ATP that acts as a ligand-gated ion channel.
Tissue Specificity Expressed predominantly in skeletal muscle.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )
Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway
Platelet homeostasis (R-HSA-418346 )
Elevation of cytosolic Ca2+ levels (R-HSA-139853 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive polycystic kidney disease DISPUS40 Definitive Altered Expression [1]
Mood disorder DISLVMWO Definitive Genetic Variation [2]
Pulmonary disease DIS6060I Definitive Biomarker [3]
Advanced cancer DISAT1Z9 Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Genetic Variation [5]
Arrhythmia DISFF2NI Strong Altered Expression [6]
Arteriosclerosis DISK5QGC Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [7]
Brain neoplasm DISY3EKS Strong Biomarker [8]
Bronchopulmonary dysplasia DISO0BY5 Strong Biomarker [9]
Carcinoma DISH9F1N Strong Biomarker [10]
Cardiac failure DISDC067 Strong Altered Expression [6]
Congestive heart failure DIS32MEA Strong Altered Expression [6]
Cystic fibrosis DIS2OK1Q Strong Altered Expression [11]
Dengue DISKH221 Strong Biomarker [12]
Depression DIS3XJ69 Strong Genetic Variation [9]
Eosinophilic esophagitis DISR8WSB Strong Genetic Variation [13]
Head and neck cancer DISBPSQZ Strong Altered Expression [14]
Head and neck carcinoma DISOU1DS Strong Altered Expression [14]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [14]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [15]
High blood pressure DISY2OHH Strong Genetic Variation [16]
Hyperglycemia DIS0BZB5 Strong Biomarker [17]
Influenza DIS3PNU3 Strong Biomarker [18]
Lung cancer DISCM4YA Strong Genetic Variation [19]
Lung carcinoma DISTR26C Strong Genetic Variation [19]
Major depressive disorder DIS4CL3X Strong Biomarker [9]
Malignant soft tissue neoplasm DISTC6NO Strong Altered Expression [20]
Multiple sclerosis DISB2WZI Strong Altered Expression [21]
Myeloid leukaemia DISMN944 Strong Biomarker [22]
Narcolepsy DISLCNLI Strong Genetic Variation [23]
Neoplasm DISZKGEW Strong Biomarker [24]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [25]
Parkinson disease DISQVHKL Strong Altered Expression [26]
Pulmonary fibrosis DISQKVLA Strong Biomarker [3]
Rheumatoid arthritis DISTSB4J Strong Biomarker [27]
Sarcoma DISZDG3U Strong Altered Expression [20]
Schizophrenia DISSRV2N Strong Genetic Variation [28]
Status epilepticus seizure DISY3BIC Strong Biomarker [29]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [27]
Vascular disease DISVS67S Strong Biomarker [30]
Benign neoplasm DISDUXAD moderate Altered Expression [31]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [32]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [33]
Bipolar disorder DISAM7J2 Limited Biomarker [34]
Hepatitis DISXXX35 Limited Biomarker [35]
Neuralgia DISWO58J Limited Biomarker [36]
Neuroblastoma DISVZBI4 Limited Altered Expression [37]
Periodontitis DISI9JOI Limited Biomarker [38]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of P2X purinoceptor 6 (P2RX6). [39]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of P2X purinoceptor 6 (P2RX6). [41]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved Temozolomide decreases the expression of P2X purinoceptor 6 (P2RX6). [40]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of P2X purinoceptor 6 (P2RX6). [42]
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References

1 Characterization of purinergic receptor expression in ARPKD cystic epithelia.Purinergic Signal. 2018 Dec;14(4):485-497. doi: 10.1007/s11302-018-9632-5. Epub 2018 Nov 11.
2 The P2RX7 polymorphism rs2230912 is associated with depression: A meta-analysis.Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:272-277. doi: 10.1016/j.pnpbp.2017.11.003. Epub 2017 Nov 7.
3 The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and fibroblasts in fibrotic lung disease.Oncotarget. 2017 May 30;8(22):35962-35972. doi: 10.18632/oncotarget.16414.
4 Involvement of the P2X7 purinergic receptor in inflammation: an update of antagonists series since 2009 and their promising therapeutic potential.Curr Med Chem. 2015;22(6):713-29. doi: 10.2174/0929867322666141212120926.
5 Theobromine-Induced Changes in A1 Purinergic Receptor Gene Expression and Distribution in a Rat Brain Alzheimer's Disease Model.J Alzheimers Dis. 2017;55(3):1273-1283. doi: 10.3233/JAD-160569.
6 Loss of function mutation in the P2X7, a ligand-gated ion channel gene associated with hypertrophic cardiomyopathy.Purinergic Signal. 2019 Jun;15(2):205-210. doi: 10.1007/s11302-019-09660-7. Epub 2019 May 31.
7 Deletion of P2Y2 receptor reveals a role for lymphotoxin- in fatty streak formation.Vascul Pharmacol. 2016 Oct;85:11-20. doi: 10.1016/j.vph.2016.06.001. Epub 2016 Jun 26.
8 Roles of purinergic P2X(7) receptor in glioma and microglia in brain tumors.Cancer Lett. 2017 Aug 28;402:93-99. doi: 10.1016/j.canlet.2017.05.004. Epub 2017 May 20.
9 Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms.J Affect Disord. 2013 Aug 15;150(1):104-9. doi: 10.1016/j.jad.2013.02.033. Epub 2013 Apr 18.
10 Role of purinergic receptors in hepatobiliary carcinoma in Pakistani population: an approach towards proinflammatory role of P2X4 and P2X7 receptors.Purinergic Signal. 2019 Sep;15(3):367-374. doi: 10.1007/s11302-019-09675-0. Epub 2019 Aug 10.
11 Extracellular zinc and ATP restore chloride secretion across cystic fibrosis airway epithelia by triggering calcium entry.J Biol Chem. 2004 Mar 12;279(11):10720-9. doi: 10.1074/jbc.M313391200. Epub 2003 Dec 29.
12 The purinergic receptor P2X7 role in control of Dengue virus-2 infection and cytokine/chemokine production in infected human monocytes.Immunobiology. 2016 Jul;221(7):794-802. doi: 10.1016/j.imbio.2016.02.003. Epub 2016 Feb 27.
13 Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.Nat Genet. 2014 Aug;46(8):895-900. doi: 10.1038/ng.3033. Epub 2014 Jul 13.
14 P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer.Oncotarget. 2017 Jul 25;8(30):48972-48982. doi: 10.18632/oncotarget.16903.
15 P2X3 purinergic receptor overexpression is associated with poor recurrence-free survival in hepatocellular carcinoma patients.Oncotarget. 2015 Dec 1;6(38):41162-79. doi: 10.18632/oncotarget.6240.
16 Ambulatory blood pressure is associated with polymorphic variation in P2X receptor genes.Hypertension. 2008 Nov;52(5):980-5. doi: 10.1161/HYPERTENSIONAHA.108.113282. Epub 2008 Oct 13.
17 A G(s)-coupled purinergic receptor boosts Ca(2+) influx and vascular contractility during diabetic hyperglycemia.Elife. 2019 Mar 1;8:e42214. doi: 10.7554/eLife.42214.
18 Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection.mBio. 2017 Mar 28;8(2):e00229-17. doi: 10.1128/mBio.00229-17.
19 Correlation of P2RX7 gene rs1718125 polymorphism with postoperative fentanyl analgesia in patients with lung cancer.Medicine (Baltimore). 2019 Feb;98(7):e14445. doi: 10.1097/MD.0000000000014445.
20 Cloning of P2XM, a novel human P2X receptor gene regulated by p53.Cancer Res. 1997 Aug 1;57(15):3281-7.
21 The role of vitamin D and P2X7R in multiple sclerosis.J Neuroimmunol. 2019 May 15;330:159-169. doi: 10.1016/j.jneuroim.2019.03.004. Epub 2019 Mar 14.
22 Chronic treatment with P2-purinergic receptor agonists induces phenotypic modulation of the HL-60 and U937 human myelogenous leukemia cell lines.J Leukoc Biol. 1991 Aug;50(2):109-22. doi: 10.1002/jlb.50.2.109.
23 Genetic association, seasonal infections and autoimmune basis of narcolepsy.J Autoimmun. 2013 Jun;43:26-31. doi: 10.1016/j.jaut.2013.02.003. Epub 2013 Mar 13.
24 Extracellular vesicles in cancer immune responses: roles of purinergic receptors.Semin Immunopathol. 2018 Sep;40(5):465-475. doi: 10.1007/s00281-018-0706-9. Epub 2018 Sep 12.
25 Type 2 diabetes specifically attenuates purinergic skin vasodilatation without affecting muscarinic and nicotinic skin vasodilatation and sweating.Exp Physiol. 2018 Feb 1;103(2):212-221. doi: 10.1113/EP086694. Epub 2018 Jan 10.
26 Purinergic Signalling in Parkinson's Disease: A Multi-target System to Combat Neurodegeneration.Neurochem Res. 2019 Oct;44(10):2413-2422. doi: 10.1007/s11064-019-02798-1. Epub 2019 May 4.
27 Expression and function of the P2X(7) purinergic receptor in patients with systemic lupus erythematosus and rheumatoid arthritis.Hum Immunol. 2010 Aug;71(8):818-25. doi: 10.1016/j.humimm.2010.05.008. Epub 2010 May 20.
28 Variation in the purinergic P2RX(7) receptor gene and schizophrenia.Schizophr Res. 2008 Sep;104(1-3):146-52. doi: 10.1016/j.schres.2008.05.026. Epub 2008 Jul 9.
29 P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy.Cell Death Dis. 2018 May 1;9(5):546. doi: 10.1038/s41419-018-0586-x.
30 P2X7R mutation disrupts the NLRP3-mediated Th program and predicts poor cardiac allograft outcomes.J Clin Invest. 2018 Aug 1;128(8):3490-3503. doi: 10.1172/JCI94524. Epub 2018 Jul 16.
31 Frequent loss of expression or aberrant alternative splicing of P2XM, a p53-inducible gene, in soft-tissue tumours.Br J Cancer. 1999 Jun;80(8):1185-9. doi: 10.1038/sj.bjc.6690484.
32 NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD.Eur Respir J. 2016 Jan;47(1):254-63. doi: 10.1183/13993003.02144-2014. Epub 2015 Nov 5.
33 Strong P2X4 purinergic receptor-like immunoreactivity is selectively associated with degenerating neurons in transgenic rodent models of amyotrophic lateral sclerosis.J Comp Neurol. 2008 Jan 1;506(1):75-92. doi: 10.1002/cne.21527.
34 Association between depression and the Gln460Arg polymorphism of P2RX7 gene: a dimensional approach.Am J Med Genet B Neuropsychiatr Genet. 2009 Mar 5;150B(2):295-9. doi: 10.1002/ajmg.b.30799.
35 Potentiation of hepatic stellate cell activation by extracellular ATP is dependent on P2X7R-mediated NLRP3 inflammasome activation.Pharmacol Res. 2017 Mar;117:82-93. doi: 10.1016/j.phrs.2016.11.040. Epub 2016 Dec 8.
36 P2Y(12) deficiency in mouse impairs noradrenergic system in brain, and alters anxiety-like neurobehavior and memory.Genes Brain Behav. 2019 Feb;18(2):e12458. doi: 10.1111/gbb.12458. Epub 2018 Feb 9.
37 The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein.J Biol Chem. 2011 Jan 28;286(4):2596-606. doi: 10.1074/jbc.M110.200618. Epub 2010 Nov 16.
38 The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis.BMB Rep. 2018 Sep;51(9):468-473. doi: 10.5483/BMBRep.2018.51.9.126.
39 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
40 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
41 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
42 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.