P2RX3

Summary

P2RX3 (purinergic receptor P2X 3, HGNC:8534) is a protein-coding gene on chromosome 11q12.1, encoding P2X purinoceptor 3 (P56373). Extracellular ATP-activated non-selective cation channel.

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.

Source: NCBI Gene 5024 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8534
Approved symbol	P2RX3
Name	purinergic receptor P2X 3
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	P2X3
Ensembl gene	ENSG00000109991
Ensembl biotype	protein_coding
OMIM	600843
Entrez	5024

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000263314, ENST00000533436, ENST00000534820, ENST00000892409, ENST00000892410, ENST00000946168, ENST00000946169, ENST00000946170, ENST00000946171

RefSeq mRNA: 1 — MANE Select: NM_002559 NM_002559

CCDS: CCDS7953

Canonical transcript exons

ENST00000263314 — 12 exons

Exon	Start	End
ENSE00000916168	57368009	57368102
ENSE00000916169	57368372	57368437
ENSE00000916170	57369361	57369438
ENSE00001027133	57348170	57348263
ENSE00001027134	57346544	57346679
ENSE00001027135	57347415	57347478
ENSE00001027138	57347116	57347187
ENSE00001027143	57350762	57350898
ENSE00002166140	57338352	57338669
ENSE00002192498	57369884	57372396
ENSE00003538454	57349757	57349898
ENSE00003625716	57348627	57348704

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 82.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0406 / max 483.0177, expressed in 137 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114257	1.0406	137

Top tissues by expression

239 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.04	gold quality
cerebellar vermis	UBERON:0004720	75.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.92	silver quality
apex of heart	UBERON:0002098	72.58	gold quality
left testis	UBERON:0004533	70.88	gold quality
right testis	UBERON:0004534	70.82	gold quality
testis	UBERON:0000473	68.12	gold quality
heart left ventricle	UBERON:0002084	67.79	gold quality
cardiac ventricle	UBERON:0002082	67.34	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.07	gold quality
right lobe of liver	UBERON:0001114	62.41	gold quality
vena cava	UBERON:0004087	61.26	gold quality
pancreatic ductal cell	CL:0002079	60.39	silver quality
buccal mucosa cell	CL:0002336	59.21	gold quality
myocardium	UBERON:0002349	58.87	gold quality
liver	UBERON:0002107	56.65	gold quality
body of tongue	UBERON:0011876	55.69	gold quality
heart	UBERON:0000948	55.30	gold quality
sperm	CL:0000019	55.00	gold quality
male germ cell	CL:0000015	54.86	gold quality
thymus	UBERON:0002370	54.80	silver quality
heart right ventricle	UBERON:0002080	54.38	gold quality
superficial temporal artery	UBERON:0001614	53.87	gold quality
pons	UBERON:0000988	53.62	gold quality
quadriceps femoris	UBERON:0001377	53.51	gold quality
nasal cavity epithelium	UBERON:0005384	53.12	gold quality
tongue	UBERON:0001723	52.95	gold quality
left adrenal gland cortex	UBERON:0035825	52.91	gold quality
trachea	UBERON:0003126	52.81	gold quality
vastus lateralis	UBERON:0001379	52.72	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	258.46
E-ANND-3	no	1.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, RUNX1

Literature-anchored findings (GeneRIF, showing 38)

• Review. Activation of P2X(3)-containing channels is an important mediator of persistent nociceptive signalling. The data also indicate potential discrete roles for homomeric P2X(3) & heteromeric P2X(2/3) receptor activation in acute & chronic pain. (PMID:12885270)
• in fibers of human tooth pulp … may play a role in perception of dental pain (PMID:14520770)
• Effect of acute hypoxia on cloned homo- and heteromeric P2X3 receptors expressed in human embryonic kidney 293 cells. (PMID:15331767)
• negative residues in the P2X3 ATP receptor ectodomain are structural determinants for desensitization and the Ca2+-sensing modulatory sites (PMID:15475563)
• These data indicate that PKC activation can enhance both the Ca(2+) signal as well as the cation current through P2X(3)R, however it appears that the regulation is unlikely to be a result of direct phosphorylation of the receptor. (PMID:17052768)
• genetic and pharmacological approaches have provided converging evidence that activation of P2X3-containing channels is an important mediator of acute and persistent nociceptive signaling–review (PMID:18600577)
• Sodium Ferrulate may inhibit the initiation of pain and primary afferent sensitization mediated by P2X(3) receptor during chronic constriction injury. (PMID:18805451)
• These cells expressed P2X3 receptors. Suburothelial myofibroblasts may be intermediate in processing adenosine triphosphate-mediated sensory activation (PMID:19456993)
• The present data indicate a novel target, P2X3 receptors, to express the action of Cdk5 on membrane proteins involved in pain perception. (PMID:19960242)
• P2X(1) receptors showed an anti-inflammatory effect reducing NF-kappaB activation and TNF-alpha release whilst P2X(3) receptors mediated opposite response. (PMID:20110693)
• Released ATP activates P2X(3) receptors in the beta-cell plasma membrane, resulting in increased Ca(2+) and enhanced insulin secretion. (PMID:20308565)
• P2X3 positive fibres in the trigeminal sensory system were significantly increased in burning mouth syndrome patients compared with controls. (PMID:20418063)
• Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP (PMID:20699225)
• Amino acid residues constituting the agonist binding site of the human P2X3 receptor. (PMID:21098022)
• An early and broad expression of P2X3 receptors was found in prenatal dorsal root ganglion neurons. (PMID:22052556)
• HEK 293 cells are not permissive for stable P2X3 expression afer a significant time-dependent cell loss; often used in a recmbinant expression system, HEK cells represent a limiting permissive environment for P2X3 receptors. (PMID:22160848)
• one subunit of P2X2 and two subunits of P2X3 form P2X2/3 heteromeric receptors, whereas two subunits of P2X2 and one subunit of P2X6 constitute P2X2/6 receptors (PMID:22378790)
• The effects of single alanine substitutions of amino acid residues in the supposed ATP binding site of the human P2X3 receptor on the agonistic effect of nucleotide analogs. (PMID:22498660)
• Structure and function of P2RX3 is reviewed, and its role in treatment of pain is discussed. [Review Article] (PMID:22963434)
• ATP-gated P2X3 channels in enterochromaffin cells are downregulated in ulcerative colitis. (PMID:23917247)
• Data indicate that MgATP2- activates P2X1 and P2X3, but not P2X2 and P2X4 receptors. (PMID:23959888)
• Data indicate that Markov models are suitable to simulate agonist antagonist interactions at fast desensitizing receptors such as the P2X3R. (PMID:24223907)
• TRPV1-, TRPV2-, P2X3-, and parvalbumin-immunoreactivity neurons in the human nodose ganglion innervate the pharynx and epiglottis through the pharyngeal branch and superior laryngeal nerve (PMID:24764033)
• sensory proteins P2X3 and TRPV1 are in correlation with urothelial differentiation, while P2X5 and TRPV4 have unique expression patterns (PMID:24868547)
• Conformational flexibility of the agonist binding jaw of the human P2X3 receptor is a prerequisite for channel opening (PMID:24989924)
• esophagitis increases mRNA expressions of P2X3 and P2X7 receptors accompanied by up-regulation of TRPV1 and neurotrophic factors (NGF and GDNF). (PMID:25336328)
• Results demonstrate that the stoichiometry of the heterotrimeric hP2X2/3 receptor is not fixed, but determined by the relative availability of P2X2 and P2X3 subunits (PMID:26184350)
• Urothelial P2X3 receptors decreased significantly in responders after Lipotoxin instillation, but not after BoNT-A injection. (PMID:26241848)
• The results from this study demonstrate that there is a significant difference in the expression of the purinergic P2X2, P2X3 and P2X7 receptors in the different histological layers of the human urinary bladder. (PMID:26253104)
• Data indicate P2X3 purinergic receptors as potential new targets for hepatocellular carcinoma (HCC) therapy. (PMID:26517690)
• P2X3 receptor expression was up-regulated in neurons from patients with temporal lobe epilepsy. (PMID:26738991)
• conclude that the inter-subunit salt bridge between E112 and R198 of the head and dorsal fin domains, respectively, serves to control the mobility of these domains during agonist-activation of the hP2X3R (PMID:26825305)
• Data show that monoclonal antibodies directed against human P2X3 (12D4) potentiated the slow inactivating current mediated by the heteromeric purinergic receptor hP2X2/3 channel. (PMID:27129281)
• there is a relationship between the elevated expression of P2X3 receptor and P2X7 receptor in peripheral blood leukocytes and high serum epinephrine and norepinephrine levels in hyperthyroidism patients. (PMID:27312548)
• X-ray crystal structures of the human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states (PMID:27626375)
• P2X3 expressions in endometriosis endometrium and endometriotic lesions were significantly higher as compared with control endometrium, and positively correlated with pain. (PMID:28898282)
• Druggable negative allosteric site of P2X3 receptors. (PMID:29674445)
• The authors used structural, computational and functional approaches to show that a crucial acidic chamber near the nucleotide-binding pocket in human P2X3 receptors accommodates divalent ions in two distinct modes in the absence and presence of nucleotide. (PMID:31232692)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	p2rx3a	ENSDARG00000010477
danio_rerio	p2rx3b	ENSDARG00000029718
mus_musculus	P2rx3	ENSMUSG00000027071
rattus_norvegicus	P2rx3	ENSRNOG00000008552

Paralogs (6): P2RX5 (ENSG00000083454), P2RX7 (ENSG00000089041), P2RX6 (ENSG00000099957), P2RX1 (ENSG00000108405), P2RX4 (ENSG00000135124), P2RX2 (ENSG00000187848)

Protein

Protein identifiers

P2X purinoceptor 3 — P56373 (reviewed: P56373)

Alternative names: ATP receptor, Purinergic receptor

All UniProt accessions (2): P56373, H0YDR6

UniProt curated annotations — full annotation on UniProt →

Function. Extracellular ATP-activated non-selective cation channel. Plays particularly important role in sensory neurons where its activation is critical for gustatory, nociceptive responses, visceral reflexes and sensory hypersensitization.

Subunit / interactions. Homotrimer. Forms heterotrimer with P2RX2. Heterotrimeric P2RX2/3 has a ligand dose-response profile that is distinct from either homotrimeric P2RX2 or P2RX3.

Subcellular location. Cell membrane.

Activity regulation. Has high sensitivity to ATP. Fast activation by external ATP. Exhibits rapid desensitization. Sensitives to the ATP agonist:alpha/beta-methylene-ATP. Subject to allosteric inhibition by AF-219. Mg(2+) and Ca(2+) slow deactivation of P2RX3.

Domain organisation. Contains extracellular allosteric binding sites-distinct from the orthosteric binding site.

Similarity. Belongs to the P2X receptor family.

RefSeq proteins (1): NP_002550* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001429	P2X_purnocptor	Family
IPR003046	P2X3_purnocptor	Family
IPR027309	P2X_extracellular_dom_sf	Homologous_superfamily
IPR053792	P2X_RECEPTOR_CS	Conserved_site
IPR059116	P2X_receptor	Family

Pfam: PF00864

Catalyzed reactions (Rhea), 2 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (78 total): strand 19, helix 17, binding site 10, mutagenesis site 9, disulfide bond 5, glycosylation site 4, turn 4, topological domain 3, transmembrane region 2, chain 1, sequence variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
9UX4	ELECTRON MICROSCOPY	2.57
9IK1	ELECTRON MICROSCOPY	2.61
9UX3	ELECTRON MICROSCOPY	2.64
9UX2	ELECTRON MICROSCOPY	2.73
5SVK	X-RAY DIFFRACTION	2.77
5SVL	X-RAY DIFFRACTION	2.9
21DX	ELECTRON MICROSCOPY	2.95
9UX1	ELECTRON MICROSCOPY	2.98
5SVJ	X-RAY DIFFRACTION	2.98
5SVM	X-RAY DIFFRACTION	3.09
5SVR	X-RAY DIFFRACTION	3.13
5SVQ	X-RAY DIFFRACTION	3.25
6AH4	X-RAY DIFFRACTION	3.3
5SVP	X-RAY DIFFRACTION	3.3
21FG	ELECTRON MICROSCOPY	3.34
5YVE	X-RAY DIFFRACTION	3.4
5SVT	X-RAY DIFFRACTION	3.79
6AH5	X-RAY DIFFRACTION	3.82
5SVS	X-RAY DIFFRACTION	4.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56373-F1	88.80	0.71

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (10): 111; 158; 158; 172; 275; 279; 281; 299; 63; 65

Disulfide bonds (5): 107–153, 116–137, 122–147, 203–213, 247–256

Glycosylation sites (4): 139, 170, 194, 290

Mutagenesis-validated functional residues (9):

Position	Phenotype
61	decreases sensitivity to the allosteric inhibitor af-219.
176	does not affect the inhibition the allosteric inhibitor af-219.
178	does not affect the inhibition the allosteric inhibitor af-219.
189	abolishes the inhibition by the allosteric inhibitor af-219.
190	decreases sensitivity to the allosteric inhibitor af-219.
238	decreases sensitivity to the allosteric inhibitor af-219.
264	decreases sensitivity to the allosteric inhibitor af-219.
265	decreases sensitivity to the allosteric inhibitor af-219.
267	does not affect the inhibition he allosteric inhibitor af-219.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-139853	Elevation of cytosolic Ca2+ levels
R-HSA-418346	Platelet homeostasis

MSigDB gene sets: 176 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_328, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_RESPONSE_TO_COLD, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, TERAMOTO_OPN_TARGETS_CLUSTER_8, GOBP_CELLULAR_RESPONSE_TO_ATP

GO Biological Process (29): response to hypoxia (GO:0001666), signal transduction (GO:0007165), neuromuscular synaptic transmission (GO:0007274), response to heat (GO:0009408), response to cold (GO:0009409), response to mechanical stimulus (GO:0009612), response to carbohydrate (GO:0009743), positive regulation of calcium ion transport into cytosol (GO:0010524), urinary bladder smooth muscle contraction (GO:0014832), peristalsis (GO:0030432), regulation of synaptic plasticity (GO:0048167), behavioral response to pain (GO:0048266), positive regulation of calcium-mediated signaling (GO:0050850), sensory perception of taste (GO:0050909), establishment of localization in cell (GO:0051649), protein homotrimerization (GO:0070207), calcium ion transmembrane transport (GO:0070588), cellular response to ATP (GO:0071318), obsolete inorganic cation transmembrane transport (GO:0098662), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), chemical synaptic transmission (GO:0007268), response to temperature stimulus (GO:0009266), response to ATP (GO:0033198), monoatomic ion transmembrane transport (GO:0034220), purinergic nucleotide receptor signaling pathway (GO:0035590), modulation of chemical synaptic transmission (GO:0050804), excitatory postsynaptic potential (GO:0060079), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (7): purinergic nucleotide receptor activity (GO:0001614), extracellularly ATP-gated monoatomic cation channel activity (GO:0004931), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), monoatomic ion channel activity (GO:0005216), channel activity (GO:0015267)

GO Cellular Component (9): plasma membrane (GO:0005886), axon (GO:0030424), signaling receptor complex (GO:0043235), Schaffer collateral - CA1 synapse (GO:0098685), hippocampal mossy fiber to CA3 synapse (GO:0098686), postsynapse (GO:0098794), endomembrane system (GO:0012505), membrane (GO:0016020), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Platelet calcium homeostasis	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	3
cellular anatomical structure	3
response to temperature stimulus	2
synapse	2
response to decreased oxygen levels	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
chemical synaptic transmission	1
response to external stimulus	1
response to abiotic stimulus	1
response to oxygen-containing compound	1
positive regulation of cytosolic calcium ion concentration	1
regulation of calcium ion transport into cytosol	1
calcium ion transport into cytosol	1
positive regulation of calcium ion transmembrane transport	1
urinary tract smooth muscle contraction	1
phasic smooth muscle contraction	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
behavior	1
response to pain	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
sensory perception of chemical stimulus	1
establishment of localization	1
cellular localization	1
protein homooligomerization	1
protein trimerization	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
response to ATP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
transport	1
nucleotide receptor activity	1
purine nucleotide binding	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P2RX3	P2RX2	Q9UBL9	984
P2RX3	P2RX6	O15547	930
P2RX3	P2RX4	Q99571	917
P2RX3	P2RX1	P51575	911
P2RX3	TRPV1	Q8NER1	897
P2RX3	P2RX5	Q93086	868
P2RX3	ZNF77	Q15935	861
P2RX3	P2RX7	Q99572	798
P2RX3	P2RY2	P41231	788
P2RX3	P2RY4	P51582	775
P2RX3	P2RY6	Q15077	767
P2RX3	A0A0B4J1V8	A0A0B4J1V8	756
P2RX3	P2RY11	Q96G91	756
P2RX3	TRPA1	O75762	732
P2RX3	P2RY1	P47900	707

IntAct

12 interactions, top by confidence:

A	B	Type	Score
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): P2RX3 (Affinity Capture-MS), P2RX3 (Affinity Capture-MS)

ESM2 similar proteins: A7MB71, A8X4W9, F8W463, O73798, O97827, P05029, P15127, P15208, P18434, P18597, P18598, P21188, P25169, P30715, P30716, P33704, P33879, P43002, P49654, P50992, P51164, P51578, P54709, P56373, P97370, Q202B1, Q24046, Q3T0C6, Q3UR32, Q60489, Q63377, Q64663, Q6DE92, Q6UX71, Q80TS3, Q8IUK5, Q91VE2, Q93086, Q93235, Q99572

Diamond homologs: F8W463, O15547, O54803, O70397, P47824, P49653, P49654, P51575, P51576, P51577, P51578, P51579, P56373, Q3UR32, Q5E9U1, Q64663, Q8K3P1, Q91VE2, Q93086, Q99571, Q99572, Q9JJX6, Q9UBL9, Q9Z1M0, Q86JM7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

60 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1951 predictions. Top by Δscore:

Variant	Effect	Δscore
11:57338665:GTAGG:G	donor_gain	1.0000
11:57338668:GG:G	donor_gain	1.0000
11:57338669:GG:G	donor_gain	1.0000
11:57346542:AGGTG:A	acceptor_gain	1.0000
11:57346543:GGTGG:G	acceptor_gain	1.0000
11:57346680:G:GC	donor_loss	1.0000
11:57346681:T:G	donor_loss	1.0000
11:57347113:AAG:A	acceptor_gain	1.0000
11:57348264:G:GG	donor_gain	1.0000
11:57348702:GAA:G	donor_gain	1.0000
11:57348705:G:GG	donor_gain	1.0000
11:57349752:CCCA:C	acceptor_loss	1.0000
11:57349753:CCA:C	acceptor_loss	1.0000
11:57349754:CAG:C	acceptor_loss	1.0000
11:57349755:A:AG	acceptor_gain	1.0000
11:57349755:A:G	acceptor_loss	1.0000
11:57349755:AG:A	acceptor_gain	1.0000
11:57349755:AGG:A	acceptor_gain	1.0000
11:57349755:AGGG:A	acceptor_gain	1.0000
11:57349756:G:GA	acceptor_gain	1.0000
11:57349756:GG:G	acceptor_gain	1.0000
11:57349756:GGG:G	acceptor_gain	1.0000
11:57349756:GGGG:G	acceptor_gain	1.0000
11:57349756:GGGGA:G	acceptor_gain	1.0000
11:57366631:A:G	acceptor_gain	1.0000
11:57368098:GGAAT:G	donor_gain	1.0000
11:57368099:GAAT:G	donor_gain	1.0000
11:57368099:GAATG:G	donor_gain	1.0000
11:57368103:G:GG	donor_gain	1.0000
11:57369435:GGAG:G	donor_gain	1.0000

AlphaMissense

2631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:57348234:G:C	W152C	1.000
11:57348234:G:T	W152C	1.000
11:57350789:T:A	W245R	1.000
11:57350789:T:C	W245R	1.000
11:57350791:G:C	W245C	1.000
11:57350791:G:T	W245C	1.000
11:57350795:T:A	C247S	1.000
11:57350796:G:A	C247Y	1.000
11:57350796:G:C	C247S	1.000
11:57368418:C:A	A328D	1.000
11:57369377:A:C	D340A	1.000
11:57369377:A:T	D340V	1.000
11:57338620:G:A	G24R	0.999
11:57338620:G:C	G24R	0.999
11:57338621:G:A	G24E	0.999
11:57338633:G:C	R28P	0.999
11:57348187:T:A	C137S	0.999
11:57348188:G:C	C137S	0.999
11:57348232:T:A	W152R	0.999
11:57348232:T:C	W152R	0.999
11:57348665:T:A	I175N	0.999
11:57348672:C:A	N177K	0.999
11:57348672:C:G	N177K	0.999
11:57348682:T:C	F181L	0.999
11:57348683:T:C	F181S	0.999
11:57348683:T:G	F181C	0.999
11:57348684:C:A	F181L	0.999
11:57348684:C:G	F181L	0.999
11:57349830:T:C	C213R	0.999
11:57350795:T:C	C247R	0.999

dbSNP variants (sampled 300 via entrez): RS1000029743 (11:57340136 A>G), RS1000160591 (11:57357644 A>G), RS1000195405 (11:57358448 T>A,G), RS1000277111 (11:57357961 G>A), RS1000298628 (11:57351365 C>T), RS1000344050 (11:57345538 C>G,T), RS1000466213 (11:57340365 C>T), RS1000501722 (11:57339812 T>A), RS1000562040 (11:57359251 C>T), RS1000594640 (11:57359543 C>T), RS1000709980 (11:57368584 T>C), RS1000801175 (11:57365944 T>C), RS1000851155 (11:57346194 T>A), RS1000882221 (11:57346421 G>A), RS1000885097 (11:57364381 G>T)

Disease associations

OMIM: gene MIM:600843 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003391_7	Low high density lipoprotein cholesterol levels	4.000000e-10
GCST004600_96	Eosinophil percentage of white cells	6.000000e-09
GCST005173_36	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	5.000000e-06
GCST005174_37	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	9.000000e-06
GCST010244_418	Triglyceride levels	8.000000e-10
GCST012100_13	Hypertrophic cardiomyopathy (sarcomere positive)	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004723	coronary artery calcification
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2998 (SINGLE PROTEIN), CHEMBL3831281 (PROTEIN COMPLEX), CHEMBL4524012 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 486,843 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL3716057	GEFAPIXANT	4	386
CHEMBL265502	SURAMIN	3	36,848
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	287,353
CHEMBL5095224	ELIAPIXANT	2	115

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — P2X receptors

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
spinorphin	Negative	11.0	pIC50
TNP-ATP	Antagonist	8.9	pIC50
AF-906	Antagonist	8.9	pIC50
gefapixant	Antagonist	8.5	pIC50
sivopixant	Antagonist	8.38	pIC50
filapixant	Antagonist	8.15	pIC50
eliapixant	Antagonist	8.1	pIC50
AF353	Antagonist	8.0	pIC50
camlipixant	Antagonist	7.6	pIC50
A317491	Antagonist	7.5	pIC50
RO3	Antagonist	7.5	pIC50
ATP	Agonist	6.47	pEC50
suramin	Antagonist	4.83	pIC50

Binding affinities (BindingDB)

4641 measured of 4672 human assays (4675 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[1-[(4-chlorophenyl)methyl]-2-[4-[(5-fluoro-3-pyridinyl)oxy]anilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	0.8 nM	US-9212130: Heterocyclic derivative and pharmaceutical composition comprising the same
A-317491	KI	0.9 nM
N-[1-[(4-chlorophenyl)methyl]-2-[4-[(6-methyl-3-pyridinyl)oxy]anilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	1 nM	US-9212130: Heterocyclic derivative and pharmaceutical composition comprising the same
6-[4-[[3-[(4-chlorophenyl)methyl]-1-ethyl-2,6-dioxo-1,3-diazinan-4-yl]amino]-2-methylphenoxy]pyridine-2-carboxylic acid	IC50	1 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
6-[4-[[3-[(4-chlorophenyl)methyl]-1-ethyl-2,6-dioxo-1,3-diazinan-4-yl]amino]-2-fluorophenoxy]pyridine-2-carboxylic acid	IC50	1 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-[(5-fluoro-2-pyridinyl)oxy]anilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	1 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-(6-methylpyridazin-3-yl)oxyanilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	1 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
methyl 5-[4-[[1-[(4-chlorophenyl)methyl]-5-ethyl-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carboxylate	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
methyl 3-[4-[[1-[(4-chlorophenyl)methyl]-5-[2-(oxan-2-yloxy)ethyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]-1,2-oxazole-5-carboxylate	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
5-[4-[[1-[(4-chlorophenyl)methyl]-5-ethyl-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carboxamide	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
methyl 5-[4-[[1-[(4-chlorophenyl)methyl]-4,6-dioxo-5-propyl-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carboxylate	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
1-[(4-chlorophenyl)methyl]-3-ethyl-6-[4-[(6-nitro-3-pyridinyl)oxy]anilino]-1,3,5-triazine-2,4-dione	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
methyl 5-[3-[(4-chlorophenyl)methyl]-4-[(2-ethyl-1,3-benzothiazol-6-yl)amino]-2,6-dioxo-1,3,5-triazin-1-yl]pentanoate	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
5-[4-[[1-[(4-chlorophenyl)methyl]-4,6-dioxo-5-propyl-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carboxamide	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
N-[5-[4-[[1-[(4-chlorophenyl)methyl]-5-ethyl-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]-2-pyridinyl]acetamide	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
1-[(4-chlorophenyl)methyl]-3-[2-(oxan-2-yloxy)ethyl]-6-[4-(1,2-oxazol-3-yloxy)anilino]-1,3,5-triazine-2,4-dione	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
6-[4-[[5-methyl-1-[(4-methylcyclohexyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carbonitrile	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
6-[4-[[5-ethyl-1-[(4-methylcyclohexyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carbonitrile	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
6-[4-[[5-ethyl-1-[(4-methylcyclohexyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carboxamide	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
6-[4-[[1-[(4-chlorophenyl)methyl]-5-ethyl-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]-N-cyanopyridine-2-carboxamide	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
methyl 6-[4-[[5-ethyl-1-[(4-methylcyclohexyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]pyridazine-3-carboxylate	IC50	1 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
2-[6-oxo-3-propan-2-yl-5-(4-thiophen-3-ylphenyl)-2,4-dihydropyrrolo[3,4-c]pyrazol-4-yl]benzamide	IC50	2 nM	US-8575197: Pyrolinone derivative and pharmaceutical composition comprising the same
N-(2-hydroxyethyl)-2-[6-oxo-3-propan-2-yl-5-(4-thiophen-3-ylphenyl)-2,4-dihydropyrrolo[3,4-c]pyrazol-4-yl]benzamide	IC50	2 nM	US-8575197: Pyrolinone derivative and pharmaceutical composition comprising the same
N-methyl-2-[6-oxo-3-propan-2-yl-5-(4-thiophen-3-ylphenyl)-2,4-dihydropyrrolo[3,4-c]pyrazol-4-yl]benzamide	IC50	2 nM	US-8575197: Pyrolinone derivative and pharmaceutical composition comprising the same
N,N-dimethyl-2-[6-oxo-3-propan-2-yl-5-(4-thiophen-3-ylphenyl)-2,4-dihydropyrrolo[3,4-c]pyrazol-4-yl]benzamide	IC50	2 nM	US-8575197: Pyrolinone derivative and pharmaceutical composition comprising the same
3-tert-butyl-4-(2-methoxyphenyl)-5-(6-thiophen-3-yl-3-pyridinyl)-2,4-dihydropyrrolo[3,4-c]pyrazol-6-one	IC50	2 nM	US-8575197: Pyrolinone derivative and pharmaceutical composition comprising the same
N-[1-[(4-chlorophenyl)methyl]-6-oxo-2-[4-(2-oxopiperidin-4-yl)oxyanilino]pyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9212130: Heterocyclic derivative and pharmaceutical composition comprising the same
N-[1-[(4-chlorophenyl)methyl]-2-[4-[(6-methyl-3-pyridinyl)oxy]anilino]-6-oxopyrimidin-5-yl]-2-hydroxy-2-methylpropanamide	IC50	2 nM	US-9212130: Heterocyclic derivative and pharmaceutical composition comprising the same
methyl 5-[4-[[1-[(4-chlorophenyl)methyl]-5-(oxane-4-carbonylamino)-6-oxopyrimidin-2-yl]amino]phenoxy]pyridine-3-carboxylate	IC50	2 nM	US-9212130: Heterocyclic derivative and pharmaceutical composition comprising the same
3-[4-[[1-[(4-chlorophenyl)methyl]-5-(oxane-4-carbonylamino)-6-oxopyrimidin-2-yl]amino]phenoxy]benzoic acid	IC50	2 nM	US-9212130: Heterocyclic derivative and pharmaceutical composition comprising the same
6-[4-[[3-[(4-chlorophenyl)methyl]-1-ethyl-2,6-dioxo-1,3-diazinan-4-yl]amino]-2-fluorophenoxy]pyridine-2-carbonitrile	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
6-[4-[[3-[(4-chlorophenyl)methyl]-1-ethyl-2,6-dioxo-1,3-diazinan-4-yl]amino]-2-methylphenoxy]pyridine-2-carbonitrile	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
2-[4-[[3-[(4-chlorophenyl)methyl]-1-ethyl-2,6-dioxo-1,3-diazinan-4-yl]amino]phenoxy]-1,3-thiazole-5-carboxylic acid	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
6-[4-[[1-[(4-chlorophenyl)methyl]-5-(oxane-4-carbonylamino)-6-oxopyrimidin-2-yl]amino]phenoxy]pyridine-2-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
6-[4-[[1-[(4-chlorophenyl)methyl]-5-ethoxycarbonyl-6-oxopyrimidin-2-yl]amino]phenoxy]pyridine-2-carboxylic acid	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-(1,2-oxazol-3-yloxy)anilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-6-oxo-2-[4-(1,3-thiazol-2-yloxy)anilino]pyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-[(3-fluoro-2-pyridinyl)oxy]anilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-[(6-fluoro-2-pyridinyl)oxy]anilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-[(6-fluoro-2-pyridinyl)oxy]-3-methylanilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-(6-methylpyrazin-2-yl)oxyanilino]-6-oxopyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
N-[1-[(4-chlorophenyl)methyl]-2-[4-(5-cyanopyrazin-2-yl)oxyanilino]-6-oxo-4,5-dihydropyrimidin-5-yl]oxane-4-carboxamide	IC50	2 nM	US-9550763: Heterocyclic ring and carbocyclic derivative
4-[4-[[1-[(4-chlorophenyl)methyl]-5-ethyl-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]-N-methylpyridine-2-carboxamide	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
methyl 5-[4-(3-chloro-4-propan-2-yloxyanilino)-3-[(4-methylphenyl)methyl]-2,6-dioxo-1,3,5-triazin-1-yl]pentanoate	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
ethyl 3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyridin-4-yloxyanilino)-1,3,5-triazin-1-yl]propanoate	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
ethyl 4-[3-[(4-methylphenyl)methyl]-2,6-dioxo-4-(4-pyridin-4-yloxyanilino)-1,3,5-triazin-1-yl]butanoate	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
1-[(4-chlorophenyl)methyl]-3-ethyl-6-[4-[4-(1H-1,2,4-triazol-5-yl)phenoxy]anilino]-1,3,5-triazine-2,4-dione	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
ethyl 3-[4-[(2-methyl-1,3-benzothiazol-6-yl)amino]-3-[(4-methylcyclohexyl)methyl]-2,6-dioxo-1,3,5-triazin-1-yl]propanoate	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
methyl 5-[4-[[5-ethyl-1-[(4-methylphenyl)methyl]-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]pyridine-2-carboxylate	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same
ethyl 2-[4-[[1-[(4-chlorophenyl)methyl]-5-ethyl-4,6-dioxo-1,3,5-triazin-2-yl]amino]phenoxy]-1,3-thiazole-5-carboxylate	IC50	2 nM	US-9718790: Triazine derivative and pharmaceutical composition having an analgesic activity comprising the same

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.32	IC50	0.0481	nM	SPINORPHIN
9.10	IC50	0.8	nM	CHEMBL3910178
9.05	EC50	0.9	nM	TNP-ATP
9.00	IC50	1	nM	CHEMBL3917952
9.00	IC50	1	nM	CHEMBL6053649
9.00	IC50	1	nM	CHEMBL5890506
9.00	IC50	1	nM	CHEMBL6059311
9.00	IC50	1	nM	CHEMBL5828119
9.00	IC50	1	nM	CHEMBL5822127
9.00	IC50	1	nM	CHEMBL5988038
9.00	IC50	1	nM	CHEMBL6023508
9.00	IC50	1	nM	CHEMBL5906764
9.00	IC50	1	nM	CHEMBL6014320
9.00	IC50	1	nM	CHEMBL6057378
9.00	IC50	1	nM	CHEMBL6020746
9.00	IC50	1	nM	CHEMBL5750119
9.00	IC50	1	nM	CHEMBL5931380
9.00	IC50	1	nM	CHEMBL5889467
9.00	IC50	1	nM	CHEMBL6051463
9.00	IC50	1	nM	CHEMBL5813666
9.00	IC50	1	nM	CHEMBL6026949
9.00	IC50	1	nM	CHEMBL5843845
9.00	IC50	1	nM	CHEMBL5999082
8.70	IC50	2	nM	CHEMBL3679934
8.70	IC50	2	nM	CHEMBL3679935
8.70	IC50	2	nM	CHEMBL3679936
8.70	IC50	2	nM	CHEMBL3679937
8.70	IC50	2	nM	CHEMBL3684651
8.70	IC50	2	nM	CHEMBL3977217
8.70	IC50	2	nM	CHEMBL3985879
8.70	IC50	2	nM	CHEMBL3891765
8.70	IC50	2	nM	CHEMBL3910668
8.70	IC50	2	nM	CHEMBL5963991
8.70	IC50	2	nM	CHEMBL5987403
8.70	IC50	2	nM	CHEMBL5919007
8.70	IC50	2	nM	CHEMBL5891540
8.70	IC50	2	nM	CHEMBL6040938
8.70	IC50	2	nM	CHEMBL6046972
8.70	IC50	2	nM	CHEMBL6058060
8.70	IC50	2	nM	CHEMBL5933802
8.70	IC50	2	nM	CHEMBL5965698
8.70	IC50	2	nM	CHEMBL5862320
8.70	IC50	2	nM	CHEMBL5854092
8.70	IC50	2	nM	CHEMBL5770574
8.70	IC50	2	nM	CHEMBL5894745
8.70	IC50	2	nM	CHEMBL5755421
8.70	IC50	2	nM	CHEMBL6031248
8.70	IC50	2	nM	CHEMBL5852812
8.70	IC50	2	nM	CHEMBL5922608
8.70	IC50	2	nM	CHEMBL5823448

PubChem BioAssay actives

541 with measured affinity, of 917 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoic acid	297380: Antagonist activity at human P2X3 receptor expressed in Xenopus oocytes assessed as inhibition of ATP-induced ion current by two electrode voltage clamping technique	ic50	<0.0001	uM
[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-1’,3’,5’-trinitrospiro[3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-2,6’-cyclohexa-1,3-diene]-6-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	150151: Antagonist activity against recombinant human P2X purinoceptor 3 (P2X3 )	ec50	0.0009	uM
N,3,5-trimethyl-4-[7-methyl-3-[(4-propanoylmorpholin-2-yl)methyl]imidazo[1,2-a]pyridin-2-yl]benzamide	1863330: Antagonist activity at human P2X3R expressed in HEK293 cells assessed as reduction in alphabeta-MeATP-induced intracellular Ca2+ influx pretreated with compound followed by alphabeta-MeATP addition and measured by Fluo-4 dye fluorescence analysis	ic50	0.0030	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-4-[4-[(6-fluoro-2-pyridinyl)oxy]anilino]-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0030	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-4-[4-[(5-fluoro-2-pyridinyl)oxy]anilino]-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0031	uM
2-[5-cyclopropyl-12-(difluoromethyl)-8-oxo-2,3,7,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,10,12-pentaen-7-yl]-N-(5-fluoro-2-pyridinyl)acetamide	2036556: Antagonist activity at human P2X3 receptor transfected in CHO cells assessed as inhibition of alpha,beta-methylene ATP induced intracellular calcium level preincubated for 10 mins followed by alpha,beta-methylene ATP addition and measured immediately by bioluminescence based analysis	ic50	0.0040	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyridin-2-yloxyanilino)-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0042	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-4-[4-[(4-fluoro-2-pyridinyl)oxy]anilino]-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid;ethane	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0049	uM
N-[4-[3-[2-(2,5-dimethoxyphenyl)ethyl]-4-oxoquinazolin-6-yl]-3-methoxyphenyl]acetamide	1627273: Antagonist activity at human P2X3 receptor expressed in recombinant HEK293 Tet-on cells assessed as inhibition of alpha-beta-methylene-ATP induced calcium release by fluo-4 dye based assay	ic50	0.0050	uM
2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol	414333: Antagonist activity at human P2X2/3 receptor expressed in 1321n1c cells by FLIPR	ic50	0.0050	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyridin-4-yloxyanilino)-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0052	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-4-[4-[(2-fluoro-4-pyridinyl)oxy]anilino]-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0054	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-4-[4-[(5-fluoro-3-pyridinyl)oxy]anilino]-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0056	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-[4-(1,2-thiazol-3-yloxy)anilino]-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0056	uM
1-[(4-chlorophenyl)methyl]-6-(3-chloro-4-propan-2-yloxyanilino)-3-[(2R)-2,3-dihydroxypropyl]-1,3,5-triazine-2,4-dione	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0057	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyrazin-2-yloxyanilino)-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0058	uM
N-[5-[3-[2-(2,5-dimethoxyphenyl)ethyl]-4-oxoquinazolin-6-yl]-6-methyl-2-pyridinyl]acetamide	1627273: Antagonist activity at human P2X3 receptor expressed in recombinant HEK293 Tet-on cells assessed as inhibition of alpha-beta-methylene-ATP induced calcium release by fluo-4 dye based assay	ic50	0.0060	uM
2-(5-cyclopropyl-8-oxo-12-propan-2-yl-2,3,7,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,10,12-pentaen-7-yl)-N-(5-fluoro-2-pyridinyl)acetamide	2036556: Antagonist activity at human P2X3 receptor transfected in CHO cells assessed as inhibition of alpha,beta-methylene ATP induced intracellular calcium level preincubated for 10 mins followed by alpha,beta-methylene ATP addition and measured immediately by bioluminescence based analysis	ic50	0.0060	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-[4-(1,3-thiazol-2-yloxy)anilino]-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0063	uM
1-[(4-chlorophenyl)methyl]-6-(3-chloro-4-propan-2-yloxyanilino)-3-[3-hydroxy-2-(hydroxymethyl)propyl]-1,3,5-triazine-2,4-dione	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0067	uM
3-[3-[(4-chlorophenyl)methyl]-4-(3-chloro-4-propan-2-yloxyanilino)-2,6-dioxo-1,3,5-triazin-1-yl]-2,2-dimethylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0067	uM
1-[(4-chlorophenyl)methyl]-6-(3-chloro-4-propan-2-yloxyanilino)-3-(3-hydroxypropyl)-1,3,5-triazine-2,4-dione	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0069	uM
6-(6-amino-2-methyl-3-pyridinyl)-3-[2-(2,5-dimethoxyphenyl)ethyl]quinazolin-4-one	1627273: Antagonist activity at human P2X3 receptor expressed in recombinant HEK293 Tet-on cells assessed as inhibition of alpha-beta-methylene-ATP induced calcium release by fluo-4 dye based assay	ic50	0.0070	uM
2-(5,12-dicyclopropyl-8-oxo-2,3,7,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,10,12-pentaen-7-yl)-N-(5-fluoro-2-pyridinyl)acetamide	2036556: Antagonist activity at human P2X3 receptor transfected in CHO cells assessed as inhibition of alpha,beta-methylene ATP induced intracellular calcium level preincubated for 10 mins followed by alpha,beta-methylene ATP addition and measured immediately by bioluminescence based analysis	ic50	0.0070	uM
2-(4,10-dicyclopropyl-7-oxo-5-thia-1,3,8,12-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,9,11-tetraen-8-yl)-N-(5-fluoro-2-pyridinyl)acetamide	2036556: Antagonist activity at human P2X3 receptor transfected in CHO cells assessed as inhibition of alpha,beta-methylene ATP induced intracellular calcium level preincubated for 10 mins followed by alpha,beta-methylene ATP addition and measured immediately by bioluminescence based analysis	ic50	0.0070	uM
2-[5-cyclopropyl-8-oxo-12-(trifluoromethyl)-2,3,7,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,10,12-pentaen-7-yl]-N-(5-fluoro-2-pyridinyl)acetamide	2036556: Antagonist activity at human P2X3 receptor transfected in CHO cells assessed as inhibition of alpha,beta-methylene ATP induced intracellular calcium level preincubated for 10 mins followed by alpha,beta-methylene ATP addition and measured immediately by bioluminescence based analysis	ic50	0.0070	uM
2-[5-(difluoromethyl)-8-oxo-12-(trifluoromethyl)-2,3,7,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,10,12-pentaen-7-yl]-N-(5-fluoro-2-pyridinyl)acetamide	2036556: Antagonist activity at human P2X3 receptor transfected in CHO cells assessed as inhibition of alpha,beta-methylene ATP induced intracellular calcium level preincubated for 10 mins followed by alpha,beta-methylene ATP addition and measured immediately by bioluminescence based analysis	ic50	0.0070	uM
(2S)-3-[4-(3-chloro-4-propan-2-yloxyanilino)-3-[(4-methylphenyl)methyl]-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0070	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyridazin-3-yloxyanilino)-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0077	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-4-(3-fluoro-4-propan-2-yloxyanilino)-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0078	uM
3-(5-methyl-1,3-thiazol-2-yl)-5-[(3R)-oxolan-3-yl]oxy-N-[(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl]benzamide	1863330: Antagonist activity at human P2X3R expressed in HEK293 cells assessed as reduction in alphabeta-MeATP-induced intracellular Ca2+ influx pretreated with compound followed by alphabeta-MeATP addition and measured by Fluo-4 dye fluorescence analysis	ic50	0.0080	uM
sodium (2R)-2-(2-methoxyphenyl)-3-(2-methylpropanoyl)-5-oxo-1-(4-thiophen-3-ylphenyl)-2H-pyrrol-4-olate	1624857: Antagonist activity at human P2X3 receptor expressed in rat C6BU-1 cells measured up to 3 mins by Fluo-3/AM dye-based fluorescence assay	ic50	0.0080	uM
[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-sulfanylidene-3H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1870739: Agonist activity at human P2X2R/P2X3R expressing CHO cells assessed as reduction in intracellular Ca2+ influx pretreated with Fluo-4 for 1 hr followed by compound addition and further incubated for 30 mins in presence of ATP by multimode plate reader analysis	ic50	0.0083	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyridin-3-yloxyanilino)-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0086	uM
(4E)-5-cyclohexyl-4-[hydroxy-(4-methoxyphenyl)methylidene]-1-[4-(3-methyl-1,2-oxazol-5-yl)phenyl]pyrrolidine-2,3-dione	1497295: Antagonist activity at human P2X3 receptor expressed in C6-BU-1 cells assessed as inhibition of calcium flux after 1 hr by Fluo-3AM dye based FLIPR assay	ic50	0.0090	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-4-(3-chloro-4-propan-2-yloxyanilino)-2,6-dioxo-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0090	uM
5-[(3-phenoxyphenyl)methyl-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]benzene-1,2,4-tricarboxylic acid	1627252: Antagonist activity at human P2X2/3 expressed in human1321N1 cells assessed as inhibition of alpha,beta-methylene-ATP-stimulated Ca2+ influx preincubated for 3 mins followed by alpha,beta-methylene-ATP addition measured after 3 mins by Fluo-4 assay	ki	0.0090	uM
3-[3-[(4-chlorophenyl)methyl]-4-(3-fluoro-4-propan-2-yloxyanilino)-2,6-dioxo-1,3,5-triazin-1-yl]propanenitrile	1731277: Antagonist activity at human P2X3 receptor expressed in rat C6-BU-1 cells	ic50	0.0091	uM
3-[4-(3-chloro-4-propan-2-yloxyanilino)-3-[(4-methylphenyl)methyl]-2,6-dioxo-1,3,5-triazin-1-yl]-2,2-dimethylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0098	uM
(2S)-3-[3-[(4-chlorophenyl)methyl]-2,6-dioxo-4-(4-pyrimidin-2-yloxyanilino)-1,3,5-triazin-1-yl]-2-methylpropanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0099	uM
ethyl 4-[(3E)-2-cyclohexyl-3-[hydroxy-(4-methoxyphenyl)methylidene]-4,5-dioxopyrrolidin-1-yl]benzoate	1497295: Antagonist activity at human P2X3 receptor expressed in C6-BU-1 cells assessed as inhibition of calcium flux after 1 hr by Fluo-3AM dye based FLIPR assay	ic50	0.0100	uM
4-[2-(2,5-dimethoxyphenyl)ethyl]-11-(2,2-dimethylpropanoyl)-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	1627253: Antagonist activity at human recombinant P2X3 receptor expressed in HEK293-Tet-on cells assessed as alpha,beta-methylene-ATP-stimulated Ca2+ influx by Fluo-4 assay	ic50	0.0100	uM
2-[4-[[(1R)-1-(2-methoxypyrimidin-5-yl)ethyl]amino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-5-methylbenzonitrile	1627272: Antagonist activity at human P2X3 receptor expressed in HEK293 cells assessed as inhibition of alpha-beta-methylene-ATP induced calcium release measured at 0.1 to 3 secs interval by fluo-4 dye based FLIPR assay	ic50	0.0100	uM
(4Z)-4-[hydroxy-(4-methoxyphenyl)methylidene]-1-[4-(1,2-oxazol-3-yl)phenyl]-5-pentan-3-ylpyrrolidine-2,3-dione	1624857: Antagonist activity at human P2X3 receptor expressed in rat C6BU-1 cells measured up to 3 mins by Fluo-3/AM dye-based fluorescence assay	ic50	0.0100	uM
1-[(4-chlorophenyl)methyl]-6-(3-chloro-4-propan-2-yloxyanilino)-3-[(2S)-2,3-dihydroxypropyl]-1,3,5-triazine-2,4-dione	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0104	uM
4-[(Z)-[2-cyclohexyl-1-[4-(1,2-oxazol-3-yl)phenyl]-4,5-dioxopyrrolidin-3-ylidene]-hydroxymethyl]-N-methylbenzamide	1624857: Antagonist activity at human P2X3 receptor expressed in rat C6BU-1 cells measured up to 3 mins by Fluo-3/AM dye-based fluorescence assay	ic50	0.0110	uM
3-(2,2-dimethylpropanoyl)-4-hydroxy-2-[2-(2-methoxyethoxy)phenyl]-1-(4-thiophen-3-ylphenyl)-2H-pyrrol-5-one	1624857: Antagonist activity at human P2X3 receptor expressed in rat C6BU-1 cells measured up to 3 mins by Fluo-3/AM dye-based fluorescence assay	ic50	0.0110	uM
N-[3-[3-[(4-chlorophenyl)methyl]-4-(3-fluoro-4-propan-2-yloxyanilino)-2,6-dioxo-1,3,5-triazin-1-yl]propyl]acetamide	1731277: Antagonist activity at human P2X3 receptor expressed in rat C6-BU-1 cells	ic50	0.0110	uM
5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidine-2,4-diamine	2111277: Antagonist activity at human P2X3R expressed in HEK293 cells incubated for 18 hrs by Fluo-4 dye based microplate reader assay	ic50	0.0114	uM
4-[4-(3-chloro-4-propan-2-yloxyanilino)-3-[(4-methylphenyl)methyl]-2,6-dioxo-1,3,5-triazin-1-yl]butanoic acid	1809622: Antagonist activity at P2X3 receptor (unknown origin)	ic50	0.0124	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Rotenone	decreases expression, increases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
alpha,beta-methyleneadenosine 5’-triphosphate	increases activity, increases abundance, decreases reaction, affects binding	1
ethyl-p-hydroxybenzoate	decreases expression	1
quercitrin	increases expression	1
sulforaphane	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
A-317491	affects binding, decreases activity	1
pyrimidifen	decreases expression	1
picoxystrobin	decreases expression	1
Antimycin A	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcium	increases abundance, increases activity, decreases reaction, affects binding	1
Diethylhexyl Phthalate	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Trichloroethylene	decreases reaction, increases abundance, increases activity, affects binding, decreases activity	1
Gold Compounds	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	increases expression	1

ChEMBL screening assays

150 unique, capped per target: 109 binding, 41 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069588	Functional	Antagonist activity at human P2X3 receptor	Discovery and optimization of RO-85, a novel drug-like, potent, and selective P2X3 receptor antagonist. — Bioorg Med Chem Lett
CHEMBL2327436	Binding	Antagonist activity at human P2X3 expressed in rat liver endothelium cells assessed as inhibition of the intracellular calcium increase after 30 to 40 mins by FLIPR assay	Ion channels as therapeutic targets: a drug discovery perspective. — J Med Chem

Cellosaurus cell lines

7 cell lines: 6 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0YG	B’SYS CHO P2X3	Spontaneously immortalized cell line	Female
CVCL_D6U2	HEK293 P2RX2(B)+P2RX3	Transformed cell line	Female
CVCL_D6U3	HEK293 P2RX3	Transformed cell line	Female
CVCL_E2Y4	HEK293 P2RX2(B)V60L+P2RX3	Transformed cell line	Female
CVCL_E2Y5	HEK293 P2RX2(B)D273Y+P2RX3	Transformed cell line	Female
CVCL_E2Y6	HEK293 P2RX2(B)G353R+P2RX3	Transformed cell line	Female
CVCL_E5JC	HEK293/P2X3	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.