P2RX1

Summary

P2RX1 (purinergic receptor P2X 1, HGNC:8533) is a protein-coding gene on chromosome 17p13.2, encoding P2X purinoceptor 1 (P51575). ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and with relatively high calcium permeability.

The protein encoded by this gene belongs to the P2X family of G-protein-coupled receptors. These proteins can form homo-and heterotimers and function as ATP-gated ion channels and mediate rapid and selective permeability to cations. This protein is primarily localized to smooth muscle where binds ATP and mediates synaptic transmission between neurons and from neurons to smooth muscle and may being responsible for sympathetic vasoconstriction in small arteries, arterioles and vas deferens. Mouse studies suggest that this receptor is essential for normal male reproductive function. This protein may also be involved in promoting apoptosis.

Source: NCBI Gene 5023 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 94 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8533
Approved symbol	P2RX1
Name	purinergic receptor P2X 1
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	P2X1
Ensembl gene	ENSG00000108405
Ensembl biotype	protein_coding
OMIM	600845
Entrez	5023

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000225538, ENST00000571637, ENST00000572418, ENST00000576764, ENST00000861554, ENST00000861555, ENST00000861556, ENST00000968387, ENST00000968388, ENST00000968389

RefSeq mRNA: 1 — MANE Select: NM_002558 NM_002558

CCDS: CCDS11040

Canonical transcript exons

ENST00000225538 — 12 exons

Exon	Start	End
ENSE00000670894	3903551	3903631
ENSE00000670897	3903928	3904024
ENSE00001134812	3916089	3916465
ENSE00003468550	3899634	3899761
ENSE00003506927	3903202	3903343
ENSE00003539072	3904858	3904929
ENSE00003539815	3898484	3898549
ENSE00003567533	3898009	3898110
ENSE00003570591	3905220	3905367
ENSE00003600494	3896592	3897879
ENSE00003691870	3904330	3904399
ENSE00003693597	3898934	3899024

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 98.31.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2012 / max 453.1907, expressed in 393 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163891	4.8662	383
163890	0.2575	42
163885	0.0765	29
163886	0.0010	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	98.31	gold quality
tibial artery	UBERON:0007610	98.31	gold quality
saphenous vein	UBERON:0007318	97.04	gold quality
body of pancreas	UBERON:0001150	95.01	gold quality
monocyte	CL:0000576	93.53	gold quality
granulocyte	CL:0000094	93.36	gold quality
mononuclear cell	CL:0000842	93.04	gold quality
leukocyte	CL:0000738	92.63	gold quality
lower esophagus mucosa	UBERON:0035834	90.30	gold quality
blood	UBERON:0000178	89.76	gold quality
right coronary artery	UBERON:0001625	88.41	gold quality
bone marrow cell	CL:0002092	88.08	gold quality
left coronary artery	UBERON:0001626	87.20	gold quality
spleen	UBERON:0002106	86.93	gold quality
urinary bladder	UBERON:0001255	86.52	gold quality
superficial temporal artery	UBERON:0001614	86.34	gold quality
coronary artery	UBERON:0001621	86.15	gold quality
blood vessel layer	UBERON:0004797	86.00	gold quality
aorta	UBERON:0000947	85.82	gold quality
bone marrow	UBERON:0002371	84.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.30	gold quality
rectum	UBERON:0001052	83.20	gold quality
small intestine	UBERON:0002108	83.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.97	gold quality
endocervix	UBERON:0000458	82.92	gold quality
right lung	UBERON:0002167	82.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.59	gold quality
lower esophagus	UBERON:0013473	81.58	gold quality
mucosa of transverse colon	UBERON:0004991	80.91	gold quality
seminal vesicle	UBERON:0000998	80.88	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	16.36
E-CURD-112	yes	11.62
E-MTAB-6701	yes	9.64
E-MTAB-10042	yes	8.75
E-MTAB-9801	yes	7.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1

miRNA regulators (miRDB)

77 targeting P2RX1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357

Literature-anchored findings (GeneRIF, showing 40)

• Ionotropic P2X1 receptors may play a priming role in the subsequent activation of metabotropic P2Y receptors during platelet stimulation. (PMID:11815371)
• P2X1 ion channel acts as a positive regulator of platelet responses to collagen. (PMID:11816716)
• role of tyrosine residues essential for function (PMID:12135734)
• Mediates activation of extracellular signal-regulated kinase 2 and contributes to platelet secretion and aggregation induced by collagen (PMID:12239162)
• early, transient Ca2+ influx via P2X1 receptors can contribute to platelet activation by stimulating a significant morphological change, but does not readily synergise with P2Y12 receptors to support aggregation (PMID:12353081)
• plays a role in hemostasis and thrombosis through its participation in collagen-, thromboxane A(2)-, and shear stress-triggered platelet responses (PMID:12521992)
• Decreased expression of the contractile P2X1 receptor could lead to reduced vascular tonus and increased blood flow. (PMID:12791671)
• ATP is the principal physiologic agonist at P2X1 receptors and it plays a role in the activation of platelets. (PMID:12907444)
• the P2X1-ERK2-Myosin Light Chain Kinase axis contributes to collagen-induced platelet activation by enhancing platelet degranulation (PMID:14500714)
• Detrusor nerve varicosities from sensory urgency patients revealed general loss of all presynaptic P2X subtypes with the proportion containing receptors reducing to only 0.5-5% depending on P2X subtype. (PMID:14557870)
• P2X1 stimulation can induce/potentiate platelet activation in combination with other platelet agonists (PMID:14675100)
• residues Lys-68, Phe-185, Phe-291, Arg-292, and Lys-309 contribute to ligand binding at P2X(1) receptors, with Phe-185 and Phe-291 coordinating the binding of the adenine ring of ATP (PMID:14699168)
• the P2X(1) ion channel induces MLC-mediated cytoskeletal rearrangements, thus contributing to SIPA and degranulation during VWF-triggered platelet activation (PMID:15087444)
• P2X1 receptors are expressed in human cardiomyocytes and mainly distributed in the regions of intercalated discs; there is some close association of P2X1 receptors and connexin43 in some, not all, regions. (PMID:15686781)
• Results suggest that lipid rafts play an important role in P2X1 receptor-mediated control of arteries. (PMID:16006561)
• P2X1 receptors have a role in the early collagen-evoked intracellular Ca2+ responses of human platelets (PMID:16113781)
• glycine 250 substitution by serine gave functional responses to ATP with no effect on ATP sensitivity but a reduction in peak amplitude to P2X1 receptors (PMID:16236030)
• P2X receptor-mediated contractions of human pregnant uterus to alpha,beta-meATP and EFS, but not to ATP, are increased with the progression of pregnancy (PMID:16359770)
• P2X(1) and ERK2 both participate in shear stress controlled thrombosis, but ERK2 activation is initiated predominantly via GPIb-VWF interactions. (PMID:16420578)
• identified and characterized the P2X1 promoter utilized in MEG-01 cells and showed that binding of Sp1/3 and NF-1 to elements in the direct vicinity of the transcription start site is essential for basal transcription (PMID:16529657)
• We conclude that lipid rafts play a significant role in the regulation of P2X1 but not P2Y1 receptors in human platelets and that a reserve of non-functional P2X1 receptors may exist. (PMID:16546137)
• analysis of a novel interaction between platelet P2X1 and thrombin receptors, with P2X1 functioning to amplify aggregation responses at low levels of thrombin receptor stimulation (PMID:16634759)
• Co-expression of T18A and K367A mutant P2X1 receptors produced larger ATP evoked responses than either mutant alone and suggests that these amino and carboxy terminal regions interact to regulate channel function (PMID:16997281)
• P2X1 mRNA expression may occur as a result of an increased component of neural ATP release in the aging bladder. (PMID:17399929)
• PAR4-pretreated platelets, epinephrine caused dense granule secretion, and subsequent signaling from the ATP-gated P2X(1)-receptor and the alpha(2A)-adrenergic receptor induced aggregation. (PMID:18480058)
• analysis of ectodomain lysines and suramin block of P2X1 receptors (PMID:18765669)
• Expression and localization of the nucleotide selective P(2Y2) and P(2X1) receptors suggest that these receptors may mediate ATP-induced vasodilation in skeletal muscle. (PMID:19118095)
• Data confirmed the presence of functional P2X1, P2X4 and P2X7 receptors in LAD2 cells and HLMCs. (PMID:19552691)
• Activation of P2X1 ion channels by adenosine triphosphate (ATP) promotes neutrophil chemotaxis via Rho kinase-dependent actomyosin-mediated contraction at the cell rear. (PMID:19635923)
• Expression is reduced in typ3 2 diabetes, not due to alterations in receptor distribution and mRNA expression, but may be due to differences in receptor sensitivity. (PMID:19808895)
• TLR2/1 agonist-induced platelet aggregation and secretion depends on a P2X1-mediated Ca2+ mobilisation, production of TxA2 and ADP receptor activation (PMID:20024498)
• Studies indicate that release of ATP and the subsequent activation of P2 receptors help establish the basal level of activation for signal transduction pathways and regulate a wide array of responses. (PMID:20068232)
• P2X(1) receptors showed an anti-inflammatory effect reducing NF-kappaB activation and TNF-alpha release. (PMID:20110693)
• PMA-evoked Ca(2+)entry results from an NCX3-dependent dense granule secretion and subsequent P(2X1) receptor activation by secreted ATP, rather than activation of a novel NCCE pathway. (PMID:20345709)
• these studies demonstrate for the first time an important role of receptor recycling on P2X1 receptor responsiveness (PMID:20374431)
• T-cell receptor stimulation results in the translocation of P2X1 and P2X4 receptors and pannexin-1 hemichannels to the immune synapse. (PMID:20660288)
• Lipid raft association and cholesterol sensitivity of P2X1-4 receptors for ATP (PMID:20699225)
• Cysteine scanning mutagenesis (residues Glu52-Gly96) of the human P2X1 receptor for ATP: mapping agonist binding and channel gating. (PMID:21690089)
• the cytoskeleton plays an important role in P2X1 receptor regulation (PMID:21757694)
• Studies indicate that P2X1, P2X2, and P2X4 receptors are detected in preglomerular microvessels. (PMID:21768526)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	p2rx1	ENSDARG00000016695
mus_musculus	P2rx1	ENSMUSG00000020787
rattus_norvegicus	P2rx1	ENSRNOG00000017606

Paralogs (6): P2RX5 (ENSG00000083454), P2RX7 (ENSG00000089041), P2RX6 (ENSG00000099957), P2RX3 (ENSG00000109991), P2RX4 (ENSG00000135124), P2RX2 (ENSG00000187848)

Protein

Protein identifiers

P2X purinoceptor 1 — P51575 (reviewed: P51575)

Alternative names: ATP receptor, Purinergic receptor

All UniProt accessions (2): P51575, I3L3H3

UniProt curated annotations — full annotation on UniProt →

Function. ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and with relatively high calcium permeability. Furthermore, CTP functions as a weak affinity agonist for P2RX1. Plays a role a role in urogenital, immune and cardiovascular function. Specifically, plays an important role in neurogenic contraction of smooth muscle of the vas deferens, and therefore is essential for normal male reproductive function. In addition, contributes to smooth muscle contractions of the urinary bladder. On platelets, contributes to platelet activation and aggregation and thereby, also to thrombosis. On neutrophils, it is involved in chemotaxis and in mitigating the activation of circulating cells.

Subunit / interactions. Functional P2XRs are organized as homomeric and heteromeric trimers. Forms heterodimer with P2RX2. Forms heterodimer with P2RX4. Forms heterodimer with P2RX5.

Subcellular location. Cell membrane.

Tissue specificity. Expressed on neutrophils and platelets. Expressed on urinary bladder smooth muscle.

Activity regulation. Activated by low concentrations of ATP (<1 uM). Undergoes rapid desensitisation. Sensitives to the ATP agonist:alpha/beta-methylene-ATP. Modulated by cholesterol.

Domain organisation. The N-terminal 20 to 23 and 27 to 29 residues seem to play a role in the cholesterol-dependent gating of this receptor.

Similarity. Belongs to the P2X receptor family.

RefSeq proteins (1): NP_002549* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001429	P2X_purnocptor	Family
IPR003044	P2X1_purnocptor	Family
IPR027309	P2X_extracellular_dom_sf	Homologous_superfamily
IPR053792	P2X_RECEPTOR_CS	Conserved_site
IPR059116	P2X_receptor	Family

Pfam: PF00864

Catalyzed reactions (Rhea), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (35 total): binding site 14, disulfide bond 5, glycosylation site 4, topological domain 3, modified residue 3, transmembrane region 2, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
9B73	ELECTRON MICROSCOPY	1.96
9C2B	ELECTRON MICROSCOPY	2.42
9B95	ELECTRON MICROSCOPY	2.61
9C2A	ELECTRON MICROSCOPY	2.74
9C2C	ELECTRON MICROSCOPY	2.9
9LXC	ELECTRON MICROSCOPY	3.1
9LX5	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51575-F1	88.09	0.63

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 (14): 70; 140; 186; 186; 286; 290; 290; 292; 292; 309; 309; 68 …

Post-translational modifications (3): 387, 388, 389

Disulfide bonds (5): 117–165, 126–149, 132–159, 217–227, 261–270

Glycosylation sites (4): 153, 184, 242, 300

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-139853	Elevation of cytosolic Ca2+ levels
R-HSA-418346	Platelet homeostasis
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 337 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_274, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, CHUNG_BLISTER_CYTOTOXICITY_DN, GOBP_PLATELET_ACTIVATION, MODULE_45, MODULE_64, HASLINGER_B_CLL_WITH_MUTATED_VH_GENES, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION

GO Biological Process (26): serotonin secretion by platelet (GO:0002554), regulation of vascular associated smooth muscle contraction (GO:0003056), monoatomic ion transport (GO:0006811), apoptotic process (GO:0006915), signal transduction (GO:0007165), insemination (GO:0007320), regulation of blood pressure (GO:0008217), neuronal action potential (GO:0019228), platelet activation (GO:0030168), response to ATP (GO:0033198), synaptic transmission, glutamatergic (GO:0035249), ceramide biosynthetic process (GO:0046513), calcium ion transmembrane transport (GO:0070588), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509), positive regulation of calcium ion import across plasma membrane (GO:1905665), regulation of synaptic vesicle exocytosis (GO:2000300), regulation of smooth muscle contraction (GO:0006940), regulation of vasoconstriction (GO:0019229), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220), purinergic nucleotide receptor signaling pathway (GO:0035590), positive regulation of monoatomic ion transport (GO:0043270), establishment of localization in cell (GO:0051649), regulation of calcium ion transport (GO:0051924), excitatory postsynaptic potential (GO:0060079), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (12): purinergic nucleotide receptor activity (GO:0001614), extracellularly ATP-gated monoatomic cation channel activity (GO:0004931), monoatomic cation channel activity (GO:0005261), ATP binding (GO:0005524), identical protein binding (GO:0042802), suramin binding (GO:0043924), protein-containing complex binding (GO:0044877), ligand-gated calcium channel activity (GO:0099604), nucleotide binding (GO:0000166), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), channel activity (GO:0015267)

GO Cellular Component (10): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), secretory granule membrane (GO:0030667), protein-containing complex (GO:0032991), specific granule membrane (GO:0035579), membrane raft (GO:0045121), postsynaptic membrane (GO:0045211), presynaptic active zone membrane (GO:0048787), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Platelet calcium homeostasis	1
Hemostasis	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ligand-gated monoatomic cation channel activity	2
binding	2
synaptic membrane	2
serotonin secretion involved in inflammatory response	1
platelet degranulation	1
establishment of localization in cell	1
exocytic process	1
regulation of smooth muscle contraction	1
vascular associated smooth muscle contraction	1
regulation of vasoconstriction	1
transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
copulation	1
multi-organism reproductive process	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
blood circulation	1
regulation of biological quality	1
action potential	1
transmission of nerve impulse	1
cell activation	1
blood coagulation	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
chemical synaptic transmission	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
regulation of cytosolic calcium ion concentration	1
neuron cellular homeostasis	1
presynapse	1

Protein interactions and networks

STRING

1568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P2RX1	P2RY12	Q9H244	976
P2RX1	P2RX6	O15547	954
P2RX1	P2RY1	P47900	954
P2RX1	P2RY2	P41231	928
P2RX1	P2RX3	P56373	911
P2RX1	P2RY14	Q15391	893
P2RX1	P2RY4	P51582	889
P2RX1	P2RX7	Q99572	872
P2RX1	P2RY6	Q15077	867
P2RX1	P2RY11	Q96G91	860
P2RX1	A0A0B4J1V8	A0A0B4J1V8	843
P2RX1	P2RX5	Q93086	816
P2RX1	P2RX2	Q9UBL9	813
P2RX1	P2RY13	Q9BPV8	785
P2RX1	PANX1	Q96RD7	767

IntAct

11 interactions, top by confidence:

A	B	Type	Score
P2RX1	CYBC1	psi-mi:“MI:0915”(physical association)	0.560
P2RX1	ATE1	psi-mi:“MI:0914”(association)	0.530
P2RX1	HSPD1	psi-mi:“MI:0915”(physical association)	0.400
	AP3D1	psi-mi:“MI:0914”(association)	0.350
P2RX1	FAM20B	psi-mi:“MI:0914”(association)	0.350
P2RX1	ATP1A3	psi-mi:“MI:0914”(association)	0.350
CYBC1	P2RX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): TMED8 (Affinity Capture-MS), GMCL1 (Affinity Capture-MS), PRMT9 (Affinity Capture-MS), GOLPH3L (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), PI4K2A (Affinity Capture-MS), ATE1 (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), ARL10 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), C17orf62 (Two-hybrid)

ESM2 similar proteins: A5A6J8, P05026, P05027, P05028, P05029, P06583, P07340, P08251, P13638, P14094, P14231, P14415, P18434, P18597, P18598, P21188, P30715, P30716, P33704, P33879, P43002, P50992, P51164, P51165, P51575, P51577, P54709, Q17QL5, Q202B1, Q24048, Q28030, Q2HZ96, Q4R4V5, Q5E9U1, Q5F362, Q5J583, Q5R6C0, Q5R8S8, Q6AY41, Q8L8W0

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, Q54J33, Q54JH4, Q553Y0, Q553Y1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	13
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

2100 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3898007:ACCGC:A	donor_gain	1.0000
17:3898008:CCGCC:C	donor_gain	1.0000
17:3898564:C:CT	acceptor_gain	1.0000
17:3898929:CTCA:C	donor_loss	1.0000
17:3898932:A:AC	donor_gain	1.0000
17:3898933:C:CC	donor_gain	1.0000
17:3899760:CC:C	acceptor_gain	1.0000
17:3899761:CC:C	acceptor_gain	1.0000
17:3903197:CATAC:C	donor_loss	1.0000
17:3903199:TACC:T	donor_loss	1.0000
17:3903200:A:AC	donor_gain	1.0000
17:3903201:C:CC	donor_gain	1.0000
17:3903201:C:CG	donor_loss	1.0000
17:3903201:CCTT:C	donor_gain	1.0000
17:3903339:TGCGC:T	acceptor_gain	1.0000
17:3903340:GCGC:G	acceptor_gain	1.0000
17:3903341:CGC:C	acceptor_gain	1.0000
17:3903341:CGCC:C	acceptor_gain	1.0000
17:3903342:GC:G	acceptor_gain	1.0000
17:3903342:GCCTG:G	acceptor_loss	1.0000
17:3903343:CC:C	acceptor_gain	1.0000
17:3903343:CCTG:C	acceptor_loss	1.0000
17:3903344:C:CC	acceptor_gain	1.0000
17:3903344:CT:C	acceptor_loss	1.0000
17:3903345:T:A	acceptor_loss	1.0000
17:3903903:G:C	donor_gain	1.0000
17:3904852:CCTCA:C	donor_loss	1.0000
17:3904853:CTCAC:C	donor_loss	1.0000
17:3904854:TCAC:T	donor_loss	1.0000
17:3904855:CA:C	donor_loss	1.0000

AlphaMissense

2643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3899727:C:G	C261S	0.999
17:3899728:A:T	C261S	0.999
17:3899732:C:A	W259C	0.999
17:3899732:C:G	W259C	0.999
17:3899734:A:G	W259R	0.999
17:3899734:A:T	W259R	0.999
17:3898094:T:G	D350A	0.998
17:3898497:C:T	G340D	0.998
17:3898509:C:T	G336D	0.998
17:3899700:C:G	C270S	0.998
17:3899701:A:T	C270S	0.998
17:3899727:C:T	C261Y	0.998
17:3903270:A:G	C227R	0.998
17:3903337:G:C	N204K	0.998
17:3903337:G:T	N204K	0.998
17:3898039:G:C	F368L	0.997
17:3898039:G:T	F368L	0.997
17:3898041:A:G	F368L	0.997
17:3898094:T:A	D350V	0.997
17:3898094:T:C	D350G	0.997
17:3898503:C:T	G338E	0.997
17:3899700:C:T	C270Y	0.997
17:3899726:A:C	C261W	0.997
17:3899727:C:A	C261F	0.997
17:3899728:A:G	C261R	0.997
17:3903269:C:G	C227S	0.997
17:3903270:A:T	C227S	0.997
17:3903583:G:C	N191K	0.997
17:3903583:G:T	N191K	0.997
17:3903960:C:A	W164C	0.997

dbSNP variants (sampled 300 via entrez): RS1000069788 (17:3910925 T>C), RS1000114431 (17:3900854 A>G), RS1000147475 (17:3901209 A>G), RS1000379976 (17:3898278 A>G), RS1000441874 (17:3896361 G>A), RS1000485310 (17:3902869 A>G), RS1000541276 (17:3905436 C>A,T), RS1000552825 (17:3912936 A>G), RS1000710348 (17:3899679 T>C), RS1000777794 (17:3896110 C>G,T), RS1000848536 (17:3914733 G>A,C), RS1001206542 (17:3900050 G>A), RS1001260956 (17:3897449 A>T), RS1001477898 (17:3909672 C>T), RS1001721439 (17:3900204 G>A)

Disease associations

OMIM: gene MIM:600845 | disease phenotypes: MIM:609821

GenCC curated gene-disease

Mondo (1): platelet-type bleeding disorder 8 (MONDO:0012354)

Orphanet (1): Bleeding disorder due to P2Y12 defect (Orphanet:36355)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005551_3	Systemic sclerosis (anti-topoisomerase-positive)	1.000000e-06
GCST90002395_237	Mean platelet volume	3.000000e-10
GCST90002400_199	Plateletcrit	5.000000e-09
GCST90002402_432	Platelet count	8.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008537	anti-topoisomerase-I-antibody-positive systemic scleroderma
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565220	Bleeding Disorder Due To P2RY12 Defect (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094 (SINGLE PROTEIN), 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: 350,927 (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
CHEMBL265502	SURAMIN	3	36,848
CHEMBL82202	PYRIDOXAL PHOSPHATE ANHYDROUS	3	26,220
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	287,353
CHEMBL2104794	SALFLUVERINE	2	37
CHEMBL536151	IMD-0354	1	469

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 (8 total), top 8:

Ligand	Action	Affinity	Parameter
TNP-ATP	Antagonist	8.9	pIC50
Ip5I	Antagonist	8.5	pIC50
MRS2159	Antagonist	8.0	pIC50
NF279	Antagonist	7.3	pIC50
ATP	Agonist	7.25	pEC50
NF023	Antagonist	6.7	pIC50
NF449	Antagonist	6.3	pIC50
suramin	Antagonist	6.0	pIC50

Binding affinities (BindingDB)

1 measured of 3 human assays (4 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SR 147778	KI	1000 nM

ChEMBL bioactivities

89 potent at pChembl≥5 of 97 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	EC50	2	nM	CHEMBL339386
8.45	IC50	3.548	nM	CHEMBL1160555
8.22	EC50	6	nM	TNP-ATP
7.72	IC50	19.2	nM	IMD-0354
7.64	IC50	23.1	nM	CHEMBL2338696
7.53	IC50	29.3	nM	CHEMBL2179173
7.50	IC50	31.6	nM	CHEMBL4640175
7.42	IC50	38.3	nM	CHEMBL2088014
7.30	IC50	50.5	nM	CHEMBL2179174
7.27	EC50	54	nM	CHEMBL336208
7.25	EC50	56	nM	ADENOSINE TRIPHOSPHATE
7.24	IC50	58	nM	CHEMBL2338695
7.20	IC50	63.1	nM	CHEMBL413145
7.15	IC50	70.6	nM	CHEMBL4644398
7.12	IC50	75.6	nM	CHEMBL2088011
7.11	IC50	76.9	nM	CHEMBL461542
7.04	IC50	91	nM	CHEMBL589733
6.92	IC50	120	nM	CHEMBL337395
6.76	IC50	172	nM	CHEMBL2088009
6.75	IC50	180	nM	CHEMBL3263056
6.74	EC50	182	nM	DIADENOSINE TETRAPHOSPHATE
6.70	IC50	199	nM	CHEMBL2088012
6.70	EC50	200	nM	DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER
6.68	IC50	210	nM	CHEMBL216504
6.66	IC50	219	nM	CHEMBL4637528
6.63	IC50	236	nM	CHEMBL1253351
6.63	IC50	236	nM	CHEMBL2313115
6.49	IC50	323	nM	CHEMBL2178702
6.47	IC50	341	nM	CHEMBL2338686
6.47	IC50	335	nM	CHEMBL4648128
6.36	IC50	439	nM	CHEMBL2313133
6.30	IC50	496	nM	CHEMBL190141
6.28	IC50	522	nM	CHEMBL2179168
6.25	IC50	567	nM	CHEMBL2179170
6.24	IC50	570	nM	IMD-0354
6.22	IC50	602	nM	CHEMBL2180149
6.18	IC50	655	nM	CHEMBL4639803
6.12	IC50	755	nM	CHEMBL2313119
6.06	IC50	869	nM	CHEMBL3628655
6.04	IC50	907	nM	CHEMBL2312822
6.04	IC50	915	nM	CHEMBL4634436
5.94	IC50	1140	nM	CHEMBL2338696
5.94	IC50	1150	nM	CHEMBL129841
5.94	EC50	1150	nM	CHEMBL129841
5.89	IC50	1300	nM	SALFLUVERINE
5.87	IC50	1340	nM	CHEMBL2179166
5.82	IC50	1530	nM	CHEMBL2313134
5.82	IC50	1514	nM	CHEMBL4583478
5.80	IC50	1600	nM	CHEMBL3104636
5.78	IC50	1660	nM	CHEMBL2313116

PubChem BioAssay actives

89 with measured affinity, of 329 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
[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-[[hydroxy-[hydroxy(phosphonooxy)phosphoryl]oxyphosphoryl]oxymethyl]oxolan-3-yl] 4-phenylbenzoate	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	0.0020	uM
[[(2R,3S,4R,5R)-5-(6-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1870736: Agonist activity at human P2X1R 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	0.0035	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	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	0.0060	uM
N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0192	uM
N-[3,5-bis(trifluoromethyl)phenyl]-4-chloro-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0231	uM
5-chloro-N-(3,5-dichlorophenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0293	uM
5-chloro-2-hydroxy-N-[3-nitro-5-(trifluoromethyl)phenyl]benzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0316	uM
5-chloro-2-hydroxy-N-[4-(trifluoromethyl)phenyl]benzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0383	uM
5-chloro-N-(3,5-difluorophenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0505	uM
[[(2R,3S,4R,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	0.0540	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	0.0560	uM
N-[3,5-bis(trifluoromethyl)phenyl]-3-chloro-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0580	uM
hexasodium;8-[[4-fluoro-3-[[3-[[3-[[2-fluoro-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	255205: Inhibitory concentration against human P2X purinoceptor 1 expressed in Xenopus laevis oocytes	ic50	0.0631	uM
N-[3,5-bis(trifluoromethyl)phenyl]-3-fluoro-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0706	uM
5-chloro-N-(3-chlorophenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0756	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0769	uM
5-chloro-2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.0910	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-1,4-diene]-6-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1852200: Antagonist activity at human P2X1R transfected in CHO-K1 cells preincubated for 30 mins followed by alpha,beta-meATP addition by luminescence based assay	ic50	0.1200	uM
5-chloro-2-hydroxy-N-(3-nitrophenyl)benzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.1720	uM
1-[2-[4-chloro-1’-(2,2-dimethylpropyl)-7-hydroxyspiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-(5-chloro-[1,3]thiazolo[5,4-b]pyridin-2-yl)urea	1151489: Antagonist activity at P2X1 receptor (unknown origin) by FLIPR assay	ic50	0.1800	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	0.1820	uM
5-chloro-N-(4-chlorophenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.1990	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-[[hydroxy(phosphonooxy)phosphoryl]methyl]phosphinic acid	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	0.2000	uM
hexasodium;8-[[3-[[3-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoylamino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	152478: The compound was evaluated for antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ic50	0.2100	uM
3-chloro-2-hydroxy-N-[3-nitro-5-(trifluoromethyl)phenyl]benzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.2190	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-5-methylbenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.2360	uM
octasodium;4-[[3-[[3,5-bis[(2,4-disulfonatophenyl)carbamoyl]phenyl]carbamoylamino]-5-[(2,4-disulfonatophenyl)carbamoyl]benzoyl]amino]benzene-1,3-disulfonate	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.2360	uM
5-chloro-N-(3,5-dimethylphenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.3230	uM
5-chloro-2-hydroxy-N-[3-(trifluoromethylsulfonyl)phenyl]benzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.3350	uM
N-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxynaphthalene-2-carboxamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.3410	uM
N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzenesulfonamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.4390	uM
N-[(2R)-1-[[(2S,3R,4S)-1-cyclohexyl-4-cyclopropyl-3,4-dihydroxybutan-2-yl]amino]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl]-1H-benzimidazole-2-carboxamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.4960	uM
5-chloro-N-(3-cyanophenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.5220	uM
N-(3-tert-butylphenyl)-5-chloro-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.5670	uM
10-benzyl-9-phenylacridin-9-ol	709131: Antagonist activity at human P2X1 receptor by cell-based calcium influx assay	ic50	0.6020	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-3-methylbenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.6550	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-5-methoxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.7550	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-3-nitrobenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.8690	uM
5-chloro-N-(4-fluorophenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.9070	uM
5-chloro-N-(3,5-dimethoxyphenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	0.9150	uM
[(2R,3S,5R)-5-[6-(methylamino)purin-9-yl]-2-(phosphonooxymethyl)oxolan-3-yl] dihydrogen phosphate	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	1.1500	uM
2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	1.3000	uM
5-chloro-N-(3-ethynylphenyl)-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	1.3400	uM
[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-sulfanylidene-3H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1870736: Agonist activity at human P2X1R 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	1.5136	uM
N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-chloro-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	1.5300	uM
1-[2-[1’-(2,2-dimethylpropyl)spiro[2H-indole-3,4’-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1062265: Antagonist activity at P2X1 receptor in HEK293 cells assessed as alpha, beta-methylene ATP-induced calcium flux by FLIPR assay	ic50	1.6000	uM
N-[3,5-bis(trifluoromethyl)phenyl]-5-fluoro-2-hydroxybenzamide	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	1.6600	uM
2-[3,5-bis(trifluoromethyl)anilino]-1-(5-chloro-2-hydroxyphenyl)ethanone	1654781: Antagonist activity at non-desensitizing human P2X1 receptor ( P2X2/P2X1 chimera) expressed in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx pre-incubated for 30 mins before ATP stimulation by FLIPR assay relative to control	ic50	1.7900	uM
[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]methylphosphonic acid	152476: Antagonist activity against recombinant human P2X purinoceptor 1 (P2X1 )	ec50	2.0000	uM
N,N-dipropylphenoxazine-10-carboxamide	709131: Antagonist activity at human P2X1 receptor by cell-based calcium influx assay	ic50	2.0200	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Ozone	affects expression, increases abundance, decreases expression	2
triphenyl phosphate	affects expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	decreases methylation, increases methylation	1
aluminum sulfate	decreases expression	1
jasplakinolide	affects localization, decreases activity, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
pinostrobin	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Microplastics	affects expression, increases abundance	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Cholesterol	decreases activity, decreases reaction	1
Cisplatin	decreases expression	1
Doxorubicin	affects expression	1
Polystyrenes	affects expression, increases abundance	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Cytochalasin D	decreases activity	1
1-Methyl-4-phenylpyridinium	increases expression	1
Soot	decreases expression, increases abundance	1

ChEMBL screening assays

55 unique, capped per target: 47 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017977	Functional	Antagonist activity at P2X1 receptor up to 10 uM	Identification and SAR of novel diaminopyrimidines. Part 2: The discovery of RO-51, a potent and selective, dual P2X(3)/P2X(2/3) antagonist for the treatment of pain. — Bioorg Med Chem Lett
CHEMBL2379686	Binding	Antagonist activity at P2X1 receptor (unknown origin)	Synthesis and structure-activity relationships of carboxylic acid derivatives of pyridoxal as P2X receptor antagonists. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 1 spontaneously immortalized cell line, 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0YE	B’SYS CHO P2X1	Spontaneously immortalized cell line	Female
CVCL_E0JL	Ubigene HeLa P2RX1 KO	Cancer cell line	Female
CVCL_E5JB	HEK293/P2X1	Transformed cell line	Female

Clinical trials (associated diseases)

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