P2RY11

Summary

P2RY11 (purinergic receptor P2Y11, HGNC:8540) is a protein-coding gene on chromosome 19p13.2, encoding P2Y purinoceptor 11 (Q96G91). Receptor for ATP and ADP coupled to G-proteins that activate both phosphatidylinositol-calcium and adenylyl cyclase second messenger systems.

The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is coupled to the stimulation of the phosphoinositide and adenylyl cyclase pathways and behaves as a selective purinoceptor. Naturally occuring read-through transcripts, resulting from intergenic splicing between this gene and an immediately upstream gene (PPAN, encoding peter pan homolog), have been found. The PPAN-P2RY11 read-through mRNA is ubiquitously expressed and encodes a fusion protein that shares identity with each individual gene product.

Source: NCBI Gene 5032 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 26 total
• Phenotypes (HPO): 30
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002566

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8540
Approved symbol	P2RY11
Name	purinergic receptor P2Y11
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	P2Y11
Ensembl gene	ENSG00000244165
Ensembl biotype	protein_coding
OMIM	602697
Entrez	5032

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000321826, ENST00000471843

RefSeq mRNA: 1 — MANE Select: NM_002566 NM_002566

CCDS: CCDS12226

Canonical transcript exons

ENST00000321826 — 2 exons

Exon	Start	End
ENSE00001242940	10113633	10115372
ENSE00001408094	10111693	10111740

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 91.89.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2784 / max 79.1623, expressed in 220 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173739	1.0897	179
173737	0.1024	56
173738	0.0863	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	91.89	gold quality
right uterine tube	UBERON:0001302	89.47	gold quality
skin of leg	UBERON:0001511	86.89	gold quality
zone of skin	UBERON:0000014	86.35	gold quality
skin of abdomen	UBERON:0001416	85.98	gold quality
lower esophagus mucosa	UBERON:0035834	85.67	gold quality
right frontal lobe	UBERON:0002810	85.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.34	gold quality
putamen	UBERON:0001874	85.23	gold quality
cerebellum	UBERON:0002037	85.20	gold quality
cerebellar hemisphere	UBERON:0002245	85.19	gold quality
cerebellar cortex	UBERON:0002129	85.13	gold quality
mucosa of transverse colon	UBERON:0004991	85.04	gold quality
spleen	UBERON:0002106	84.95	gold quality
primary visual cortex	UBERON:0002436	84.75	gold quality
nucleus accumbens	UBERON:0001882	84.74	gold quality
caudate nucleus	UBERON:0001873	84.52	gold quality
anterior cingulate cortex	UBERON:0009835	84.40	gold quality
Ammon’s horn	UBERON:0001954	84.15	gold quality
left lobe of thyroid gland	UBERON:0001120	83.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.85	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.64	gold quality
lower esophagus	UBERON:0013473	83.63	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.63	gold quality
gastrocnemius	UBERON:0001388	83.53	gold quality
lymph node	UBERON:0000029	83.50	gold quality
thyroid gland	UBERON:0002046	83.46	gold quality
temporal lobe	UBERON:0001871	83.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.38	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting P2RY11, 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-6756-5P	99.82	67.97	2466
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-6840-5P	88.69	60.91	68

Literature-anchored findings (GeneRIF, showing 33)

• expression profile in human peripheral tissues and brain regions using PCR (PMID:11690642)
• beta-NAD(e)+ is an agonist of the P2Y(11) purinoceptor and P2Y(11) is the endogenous receptor in granulocytes mediating the sustained [Ca2+]i increase responsible for their functional activatio (PMID:16926152)
• We propose that residues Arg106, Arg268, Arg307 and Glu186 are involved in ionic interactions with the phosphate moiety of ATP. Arg307 is possibly also H-bonded to N6 of ATP via the backbone carbonyl. (PMID:17338680)
• In human granulocytes, endogenous P2Y(11) proved to be responsible for NAADP+-induced cell activation, unveiling a role of NAADP+ as a pro-inflammatory cytokine. (PMID:17707504)
• oligomerization of the P2Y11 receptor with the P2Y1 receptor controls the internalization and ligand selectivity of the P2Y11 receptor (PMID:17824841)
• The P2 receptor mediating the antiapoptotic actions of ATP was identified using a combination of more selective ATP analogs, receptor expression studies, and study of downstream signaling pathways. (PMID:18056402)
• present data clearly show that P2Y purinoceptor 11 and P2Y purinoceptor 12 are expressed in human pancreatic islets (PMID:18726826)
• Inhibition of Natural killer cell response to CX3CL1 is mediated by the P2Y11 receptor. (PMID:20668227)
• Extracellular NAD stimulates mesenchymal stem cell functions through activation of P2Y11 receptor. (PMID:20964598)
• Common variants in P2RY11 are associated with narcolepsy. (PMID:21170044)
• P2Y11 receptors are abundantly and diffusely expressed intracellularly in skeletal muscle fibers. (PMID:22052557)
• The study extends on the observation of a strong multiethnic association of polymorphisms in the TCRA and P2RY11 with narcolepsy, but does not confirm the association of CPT1B/CHKB (rs5770917) in the Chinese population. (PMID:22177342)
• P2Y11 receptor mediates interferon gamma-induced IL-6 production in HaCaT cells, suggesting the importance of purinergic signaling in interferon-gamma induced skin inflammatory conditions (PMID:23461851)
• vesicular exocytosis of ATP and autocrine, positive feedback through P2Y11 receptors is required for the effective activation of macrophages (PMID:23577075)
• the physiological impact of A87T mutation of the P2Y11 receptor derives from detrimental effects on P2Y1-P2Y11 receptor interaction. (PMID:24524250)
• Suggest role for LXA4 in stimulating apical ATP secretion via pannexin-1 channels and P2RY11 purinoreceptors activation leading to an airway surface liquid layer height increase and epithelial repair. (PMID:24588705)
• Hypoxia/reoxygenation inhibits P2y11 receptor expression and its immunosuppressive activity in human dendritic cells. (PMID:26078273)
• a major role for P2X7R and P2Y11R in ATP-mediated inhibition of tumor-derived endothelial cell migration, is reported. (PMID:27586846)
• these results show hepatocellular carcinoma-specific expression of the P2Y11 receptor and its critical role in mediating ATP-inducing Ca2+ signalling and regulating cancer cell migration (PMID:28418839)
• Decreased P2Y11 signaling plays an important role in the development of narcolepsy with cataplexy. (PMID:28460015)
• this paper provides evidence that P2Y11 receptor inhibits P2X7 receptor pore formation but not calcium signaling which occurs independently of P2Y11 receptor signaling (PMID:29937766)
• These results also demonstrated a beneficial role of P2Y11R in human cardiac fibroblasts during Hypoxia/Reoxygenation (H/R) and strongly support the hypothesis that P2Y11R is a modulator of Ischemia/Reperfusion injury. (PMID:30031814)
• findings suggest that LPS and ATP accumulation in the circulation of sepsis patients suppresses T cells by promoting inappropriate P2Y11 receptor stimulation that impairs T cell metabolism and functions. (PMID:30787105)
• Our study provides evidence of a protective mechanism of P2Y11R antagonist NF340 against cytokine-induced inflammation. Therefore, targeting P2Y11R could have potential therapeutic implication in the treatment of rheumatoid arthritis. (PMID:31301116)
• The Human G Protein-Coupled ATP Receptor P2Y11 Is Associated With IL-10 Driven Macrophage Differentiation. (PMID:31447857)
• Study of eight narcolepsy-associated P2RY11 mutations showed decreased surface expression of the R307W P2Y11 mutant and a surface expression similar to wild type for the other seven mutants in HEK293 cells. (PMID:31450027)
• Frontline Science: P2Y11 receptors support T cell activation by directing mitochondrial trafficking to the immune synapse. (PMID:32531829)
• The purinergic receptor P2Y11 choreographs the polarization, mitochondrial metabolism, and migration of T lymphocytes. (PMID:32994212)
• High nocturnal sleep fragmentation is associated with low T lymphocyte P2Y11 protein levels in narcolepsy type 1. (PMID:33710305)
• The P2Y11 receptor of human M2 macrophages activates canonical and IL-1 receptor signaling to translate the extracellular danger signal ATP into anti-inflammatory and pro-angiogenic responses. (PMID:36107259)
• P2Y11/IL-1 receptor crosstalk controls macrophage inflammation: a novel target for anti-inflammatory strategies? (PMID:37016172)
• Systematic P2Y receptor survey identifies P2Y11 as modulator of immune responses and virus replication in macrophages. (PMID:37881155)
• Crosstalk between purinergic receptor P2Y11 and chemokine receptor CXCR7 is regulated by CXCR4 in human macrophages. (PMID:38472446)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	p2ry11	ENSDARG00000014929

Paralogs (7): GPR174 (ENSG00000147138), GPR146 (ENSG00000164849), GPR183 (ENSG00000169508), GPR151 (ENSG00000173250), RXFP3 (ENSG00000182631), GPR132 (ENSG00000183484), GPR141 (ENSG00000187037)

Protein

Protein identifiers

P2Y purinoceptor 11 — Q96G91 (reviewed: Q96G91)

All UniProt accessions (1): Q96G91

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for ATP and ADP coupled to G-proteins that activate both phosphatidylinositol-calcium and adenylyl cyclase second messenger systems. Not activated by UTP or UDP.

Subcellular location. Cell membrane.

Tissue specificity. Highest expression in liver and spleen.

Induction. Increased by DMSO and retinoic acid.

Miscellaneous. A chimeric transcript, characterized by the first third of PPAN exon 12 joined to P2RY11 exon 2, has been detected. It is possibly produced by trans-splicing. The chimeric transcript is widely expressed and can be induced by retinoic acid during the granulocytic differentiation of the HL-60 cell line. The resulting chimeric protein shows a much lower activity than the non-chimeric P2RY11 gene product, but qualitatively indistinguishable.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_002557* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR027677	P2Y11_rcpt	Family

Pfam: PF00001

UniProt features (21 total): topological domain 8, transmembrane region 7, glycosylation site 2, chain 1, region of interest 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96G91-F1	81.11	0.48

Functional residue map

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

Disulfide bonds (1): 102–180

Glycosylation sites (2): 4, 179

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-417957	P2Y receptors
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 137 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_G_PROTEIN_COUPLED_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_P2Y_RECEPTORS, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_ATP, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_ADENYLATE_CYCLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_ATP, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (9): defense response (GO:0006952), G protein-coupled receptor signaling pathway (GO:0007186), activation of adenylate cyclase activity (GO:0007190), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), calcium-mediated signaling (GO:0019722), neuronal signal transduction (GO:0023041), cellular response to ATP (GO:0071318), signal transduction (GO:0007165), G protein-coupled purinergic nucleotide receptor signaling pathway (GO:0035589)

GO Molecular Function (4): neurotransmitter receptor activity (GO:0030594), signaling receptor activity (GO:0038023), G protein-coupled ATP receptor activity (GO:0045031), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	2
Nucleotide-like (purinergic) receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
G protein-coupled receptor signaling pathway	2
response to stress	1
G protein-coupled receptor activity	1
positive regulation of adenylate cyclase activity	1
phospholipase C activator activity	1
intracellular signaling cassette	1
response to ATP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
purinergic nucleotide receptor signaling pathway	1
signaling receptor activity	1
molecular transducer activity	1
G protein-coupled purinergic nucleotide receptor activity	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P2RY11	PPAN	Q9NQ55	894
P2RY11	P2RY13	Q9BPV8	882
P2RY11	P2RX1	P51575	860
P2RY11	EIF3G	O75821	812
P2RY11	P2RX5	Q93086	788
P2RY11	P2RX2	Q9UBL9	763
P2RY11	P2RX3	P56373	756
P2RY11	P2RX6	O15547	752
P2RY11	P2RX4	Q99571	742
P2RY11	P2RX7	Q99572	680
P2RY11	ENTPD8	Q5MY95	609
P2RY11	PANX1	Q96RD7	591
P2RY11	ENTPD1	P49961	582
P2RY11	ENTPD3	O75355	572
P2RY11	P2RY4	P51582	566

IntAct

9 interactions, top by confidence:

A	B	Type	Score
P2RY11	TMED2	psi-mi:“MI:0915”(physical association)	0.400
P2RY11	IL37	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	P2RY11	psi-mi:“MI:0915”(physical association)	0.400
P2RY11	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
P2RY11	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
P2RY11	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	P2RY11	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): P2RY11 (Affinity Capture-RNA), P2RY11 (Affinity Capture-MS), P2RY11 (Affinity Capture-MS), P2RY11 (Affinity Capture-RNA), IL37 (Affinity Capture-MS), P2RY11 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R4IM31, A0A0R4IP11, E9QJ73, F8VQN3, O00270, O00421, O15218, O35457, O97663, P31392, P32302, P34997, P43142, P49685, Q04683, Q0II78, Q0VDU3, Q149R9, Q16570, Q3ZC80, Q67ES2, Q6XKD3, Q75ZH0, Q7TMA4, Q7TQA9, Q7TQP4, Q7TSN5, Q7TSN6, Q863H8, Q8BZR0, Q8TDV2, Q95LF2, Q95LF3, Q95LF4, Q95LF5, Q95LF7, Q95LF9, Q95LG5, Q96CH1, Q96G91

Diamond homologs: A1ZAX0, B2ZI34, F1MV99, O00270, O08858, O09047, O15974, O42179, O54798, O54799, O62709, O88855, O97666, O97967, P21451, P21729, P24053, P24530, P25101, P26684, P28088, P28336, P30550, P30937, P31391, P32247, P35346, P35370, P35371, P35377, P35414, P35463, P47211, P47748, P47751, P48302, P49660, P49683, P52500, P56479

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
P2RY11	“up-regulates activity”	GNAS	binding
P2RY11	“up-regulates activity”	GNAL	binding
P2RY11	“up-regulates activity”	GNAI1	binding
P2RY11	“up-regulates activity”	GNAI3	binding
P2RY11	“up-regulates activity”	GNAO1	binding
P2RY11	“up-regulates activity”	GNAZ	binding
P2RY11	“up-regulates activity”	GNAQ	binding
P2RY11	“up-regulates activity”	GNA14	binding
ATP(4-)	“up-regulates activity”	P2RY11	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	17
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

266 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10113628:CACAG:C	acceptor_loss	0.9900
19:10113629:ACAG:A	acceptor_loss	0.9900
19:10113630:CA:C	acceptor_loss	0.9900
19:10113631:A:AG	acceptor_gain	0.9900
19:10113632:G:A	acceptor_loss	0.9900
19:10113632:G:GA	acceptor_loss	0.9900
19:10113632:G:GG	acceptor_gain	0.9900
19:10113632:GGT:G	acceptor_gain	0.9900
19:10115126:CGGC:C	acceptor_gain	0.9900
19:10115130:C:CC	acceptor_gain	0.9900
19:10113631:AG:A	acceptor_gain	0.9800
19:10113631:AGGT:A	acceptor_gain	0.9800
19:10113632:GG:G	acceptor_gain	0.9800
19:10113632:GGTG:G	acceptor_gain	0.9800
19:10115128:GCCT:G	acceptor_loss	0.9800
19:10115129:CCTG:C	acceptor_loss	0.9800
19:10115131:T:A	acceptor_loss	0.9800
19:10111739:GG:G	donor_gain	0.9700
19:10111740:GG:G	donor_gain	0.9700
19:10113632:GGTGC:G	acceptor_gain	0.9700
19:10115127:GGC:G	acceptor_gain	0.9600
19:10111741:GTAA:G	donor_loss	0.9500
19:10111742:T:A	donor_loss	0.9500
19:10115135:G:C	acceptor_gain	0.9500
19:10115135:G:GC	acceptor_gain	0.9500
19:10111741:G:GG	donor_gain	0.9300
19:10111753:C:T	donor_gain	0.9300
19:10113624:T:TA	acceptor_gain	0.9300
19:10115128:GC:G	acceptor_gain	0.9100
19:10115129:CC:C	acceptor_gain	0.9100

AlphaMissense

2392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10113898:G:C	W95C	0.981
19:10113898:G:T	W95C	0.981
19:10114061:A:C	S150R	0.970
19:10114063:C:A	S150R	0.970
19:10114063:C:G	S150R	0.970
19:10114447:G:C	W278C	0.970
19:10114447:G:T	W278C	0.970
19:10113983:A:C	S124R	0.964
19:10113985:C:A	S124R	0.964
19:10113985:C:G	S124R	0.964
19:10114112:T:C	F167L	0.960
19:10114114:C:A	F167L	0.960
19:10114114:C:G	F167L	0.960
19:10114466:T:C	F285L	0.952
19:10114468:T:A	F285L	0.952
19:10114468:T:G	F285L	0.952
19:10113833:A:C	S74R	0.947
19:10113835:C:A	S74R	0.947
19:10113835:C:G	S74R	0.947
19:10114388:A:C	S259R	0.943
19:10114390:C:A	S259R	0.943
19:10114390:C:G	S259R	0.943
19:10113932:T:C	F107L	0.930
19:10113934:C:A	F107L	0.930
19:10113934:C:G	F107L	0.930
19:10114467:T:G	F285C	0.929
19:10114457:T:A	C282S	0.928
19:10114458:G:C	C282S	0.928
19:10113896:T:A	W95R	0.923
19:10113896:T:C	W95R	0.923

dbSNP variants (sampled 300 via entrez): RS1001315406 (19:10113348 G>A), RS1003246665 (19:10115266 A>G), RS1003399374 (19:10112297 C>A,T), RS1003619151 (19:10112377 G>C), RS1004113751 (19:10111622 CTG>C), RS1005077847 (19:10113179 C>T), RS1005655360 (19:10110218 C>A,T), RS1005698057 (19:10113024 G>A), RS1006148478 (19:10110710 G>A,C), RS1006400026 (19:10110944 G>C,T), RS1006451285 (19:10110849 G>A), RS1007496685 (19:10113597 G>A), RS1007608707 (19:10115196 G>A), RS1007657270 (19:10111891 C>A,T), RS1007874270 (19:10112805 G>A,C)

Disease associations

OMIM: gene MIM:602697 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000017	Nocturia
HP:0000709	Psychosis
HP:0000711	Restlessness
HP:0000716	Depression
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000822	Hypertension
HP:0000826	Precocious puberty
HP:0000975	Hyperhidrosis
HP:0001262	Excessive daytime somnolence
HP:0001279	Syncope
HP:0001350	Slurred speech
HP:0001513	Obesity
HP:0002019	Constipation
HP:0002076	Migraine
HP:0002307	Drooling
HP:0002360	Sleep disturbance
HP:0002494	Abnormal rapid eye movement sleep
HP:0002519	Hypnagogic hallucination
HP:0002524	Cataplexy
HP:0006896	Hypnopompic hallucination
HP:0007018	Attention deficit hyperactivity disorder
HP:0007686	Abnormal pupillary function
HP:0010534	Transient global amnesia
HP:0010535	Sleep apnea
HP:0012452	Restless legs
HP:0025233	Sleep paralysis
HP:0025235	NREM parasomnia
HP:0030014	Female sexual dysfunction
HP:0040307	Male sexual dysfunction

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002260_3	Narcolepsy	4.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524011 (PROTEIN FAMILY), CHEMBL4867 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 489,517 (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
CHEMBL752	ADENOSINE PHOSPHATE	4	165,316
CHEMBL265502	SURAMIN	3	36,848
CHEMBL14249	ADENOSINE TRIPHOSPHATE	2	287,353

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2305795	EIF3G, P2RY11, PPAN-P2RY11		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — P2Y receptors

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

Ligand	Action	Affinity	Parameter
AR-C67085	Full agonist	8.52	pEC50
NF340	Antagonist	7.7	pEC50
NF157	Antagonist	7.35	pKi
NF546	Full agonist	6.27	pEC50
suramin	Antagonist	6.0	pIC50
ATP	Full agonist	5.6	pEC50
ATPγS	Full agonist	5.5	pEC50
UTP	Full agonist	5.2	pEC50
BzATP	Full agonist	5.1	pEC50
reactive blue-2	Antagonist	5.0	pIC50
dATP	Full agonist	5.0	pEC50
ADPβS	Full agonist	4.5	pEC50
2MeSATP	Full agonist	4.3	pEC50

ChEMBL bioactivities

41 potent at pChembl≥5 of 50 total, top 39 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.80	Ki	15.85	nM	CHEMBL5289838
7.35	Ki	44.67	nM	CHEMBL413145
7.20	EC50	63.1	nM	ATPGAMMAS
7.12	Ki	75.86	nM	CHEMBL413910
6.97	Ki	107.2	nM	CHEMBL413180
6.95	Ki	112.2	nM	SURAMIN
6.89	EC50	130	nM	CHEMBL2386496
6.52	Ki	302	nM	SURAMIN
6.52	Ki	302	nM	CHEMBL266646
6.35	Ki	446.7	nM	CHEMBL405500
6.34	IC50	457.1	nM	CHEMBL413145
6.32	EC50	478.6	nM	8-CARBOXY-ISO-IANTHERAN A
6.30	EC50	500	nM	CHEMBL3634183
6.05	EC50	900	nM	CHEMBL3289393
6.05	EC50	900	nM	CHEMBL3634185
6.00	EC50	1000	nM	CHEMBL2386492
6.00	EC50	1000	nM	CHEMBL3634186
6.00	EC50	1000	nM	CHEMBL3634182
6.00	Ki	1000	nM	CHEMBL276295
5.96	EC50	1100	nM	CHEMBL3634184
5.89	EC50	1288	nM	ISO-IANTHERAN A
5.85	EC50	1400	nM	CHEMBL2386495
5.85	EC50	1400	nM	CHEMBL3634183
5.82	EC50	1500	nM	CHEMBL2386490
5.82	EC50	1500	nM	CHEMBL336292
5.77	EC50	1700	nM	ADENOSINE DIPHOSPHATE
5.62	Ki	2399	nM	CHEMBL409304
5.54	EC50	2900	nM	CHEMBL2181938
5.52	EC50	3000	nM	ATPGAMMAS
5.50	EC50	3200	nM	CHEMBL3634182
5.48	EC50	3300	nM	ADENOSINE TRIPHOSPHATE
5.43	EC50	3680	nM	CHEMBL3392138
5.35	EC50	4500	nM	CHEMBL575257
5.17	EC50	6700	nM	ADENOSINE TRIPHOSPHATE
5.16	EC50	7000	nM	CHEMBL339386
5.12	Ki	7586	nM	CHEMBL411554
5.06	EC50	8700	nM	CHEMBL575257
5.05	EC50	9000	nM	CHEMBL335538
5.04	EC50	9100	nM	CHEMBL3634184

PubChem BioAssay actives

40 with measured affinity, of 132 total; 30 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
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	254596: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=7	ki	0.0447	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] dihydroxyphosphinothioyl hydrogen phosphate	302984: Agonist activity at P2Y11 receptor expressed in 1321N1 cells assessed as cytosolic calcium level	ec50	0.0631	uM
hexasodium;8-[[4-methoxy-3-[[3-[[3-[[2-methoxy-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	254596: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=7	ki	0.0759	uM
hexasodium;8-[[4-chloro-3-[[3-[[3-[[2-chloro-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	254596: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=7	ki	0.1071	uM
8-[[4-methyl-3-[[3-[[3-[[2-methyl-5-[(4,6,8-trisulfonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonic acid	254593: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=3	ki	0.1122	uM
73353445	751212: Agonist activity at human GFP-tagged P2Y11R transfected in human 1321N1 cells assessed as induction of intracellular calcium mobilization by fluorescence assay	ec50	0.1300	uM
hexasodium;8-[[4-phenyl-3-[[3-[[3-[[2-phenyl-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	254593: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=3	ki	0.3020	uM
hexasodium;8-[[4-propan-2-yl-3-[[3-[[3-[[2-propan-2-yl-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	254593: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=3	ki	0.4467	uM
disodium;[(1Z,3Z)-1-[7-bromo-2-(3-bromo-4-hydroxyphenyl)-1-benzofuran-5-yl]-4-[7-bromo-2-(3-bromo-4-hydroxyphenyl)-3-carboxy-1-benzofuran-5-yl]-3-sulfonatooxybuta-1,3-dien-2-yl] sulfate	302984: Agonist activity at P2Y11 receptor expressed in 1321N1 cells assessed as cytosolic calcium level	ec50	0.4786	uM
[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl] dihydrogen phosphate	1256111: Agonist activity at GFP-tagged human P2Y11R transfected in human 1321N1 cells assessed as increase in intracellular Ca2+ level by fura 2/AM probe-based fluorescence assay	ec50	0.5000	uM
[(2R,3S,4R,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydroxyphosphinothioyl hydrogen phosphate	1256111: Agonist activity at GFP-tagged human P2Y11R transfected in human 1321N1 cells assessed as increase in intracellular Ca2+ level by fura 2/AM probe-based fluorescence assay	ec50	0.9000	uM
[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-hydroxyphosphoryl]methylphosphonic acid	1153893: Agonist activity at human P2Y11 receptor expressed in human 1321N1 cells assessed as increase of intracellular calcium level after 30 mins using fura-2 AM by fluorescence assay	ec50	0.9000	uM
hexasodium;8-[[4-ethyl-3-[[3-[[3-[[2-ethyl-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	254593: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=3	ki	1.0000	uM
[[(2R,3S,4R,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl] dihydrogen phosphate	1256111: Agonist activity at GFP-tagged human P2Y11R transfected in human 1321N1 cells assessed as increase in intracellular Ca2+ level by fura 2/AM probe-based fluorescence assay	ec50	1.0000	uM
[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydroxyphosphinothioyl hydrogen phosphate	1256111: Agonist activity at GFP-tagged human P2Y11R transfected in human 1321N1 cells assessed as increase in intracellular Ca2+ level by fura 2/AM probe-based fluorescence assay	ec50	1.0000	uM
73351984	751212: Agonist activity at human GFP-tagged P2Y11R transfected in human 1321N1 cells assessed as induction of intracellular calcium mobilization by fluorescence assay	ec50	1.0000	uM
[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl] phosphono hydrogen phosphate	1256111: Agonist activity at GFP-tagged human P2Y11R transfected in human 1321N1 cells assessed as increase in intracellular Ca2+ level by fura 2/AM probe-based fluorescence assay	ec50	1.1000	uM
disodium;[(1Z,3Z)-1,4-bis[7-bromo-2-(3-bromo-4-hydroxyphenyl)-1-benzofuran-5-yl]-3-sulfonatooxybuta-1,3-dien-2-yl] sulfate	302984: Agonist activity at P2Y11 receptor expressed in 1321N1 cells assessed as cytosolic calcium level	ec50	1.2882	uM
73347374	751212: Agonist activity at human GFP-tagged P2Y11R transfected in human 1321N1 cells assessed as induction of intracellular calcium mobilization by fluorescence assay	ec50	1.4000	uM
[[[[(2R,3S,4R,5R)-5-(6-amino-2-propylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]-dichloromethyl]phosphonic acid	150489: Agonist activity against phospholipase C coupled human P2Y purinoceptor 11 (P2Y11)	ec50	1.5000	uM
[(2R,3R,4S,5R)-2-(6-amino-2-methylsulfanylpurin-9-yl)-4-hydroxy-5-[[hydroxy(phosphonooxy)phosphoryl]oxymethyl]oxolan-3-yl] benzoate	751212: Agonist activity at human GFP-tagged P2Y11R transfected in human 1321N1 cells assessed as induction of intracellular calcium mobilization by fluorescence assay	ec50	1.5000	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1256111: Agonist activity at GFP-tagged human P2Y11R transfected in human 1321N1 cells assessed as increase in intracellular Ca2+ level by fura 2/AM probe-based fluorescence assay	ec50	1.7000	uM
hexasodium;8-[[4-(methoxymethyl)-3-[[3-[[3-[[2-(methoxymethyl)-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoyl]phenyl]carbamoylamino]benzoyl]amino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	254594: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=4	ki	2.3988	uM
71450314	751212: Agonist activity at human GFP-tagged P2Y11R transfected in human 1321N1 cells assessed as induction of intracellular calcium mobilization by fluorescence assay	ec50	2.9000	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	605231: Agonist activity at GFP tagged-human P2Y11 receptor expressed in human 1321N1 cells assessed as elevation in calcium level after 30 mins by fluorescence spectrophotometric analysis	ec50	3.3000	uM
118725181	751212: Agonist activity at human GFP-tagged P2Y11R transfected in human 1321N1 cells assessed as induction of intracellular calcium mobilization by fluorescence assay	ec50	3.6800	uM
[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl] dihydrogen phosphate	1256111: Agonist activity at GFP-tagged human P2Y11R transfected in human 1321N1 cells assessed as increase in intracellular Ca2+ level by fura 2/AM probe-based fluorescence assay	ec50	4.5000	uM
[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-4-hydroxy-5-[[hydroxy-[hydroxy(phosphonooxy)phosphoryl]oxyphosphoryl]oxymethyl]oxolan-3-yl] 4-phenylbenzoate	150489: Agonist activity against phospholipase C coupled human P2Y purinoceptor 11 (P2Y11)	ec50	7.0000	uM
hexasodium;8-[[4-methyl-3-[[2-methyl-5-[(4,6,8-trisulfonatonaphthalen-1-yl)carbamoyl]phenyl]carbamoylamino]benzoyl]amino]naphthalene-1,3,5-trisulfonate	254593: Inhibitory concentration against P2Y purinoceptor 11 expressed in 1321N1 astrocytoma cells; n=3	ki	7.5858	uM
[[(2R,3S,5R)-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	150489: Agonist activity against phospholipase C coupled human P2Y purinoceptor 11 (P2Y11)	ec50	9.0000	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
NF157 compound	affects binding, decreases activity	2
Cisplatin	decreases expression, affects binding, increases response to substance, affects cotreatment	2
aristolochic acid I	increases expression	1
Esketamine	increases expression	1
quercitrin	increases expression	1
sulforaphane	increases expression	1
adenosine 5’-O-(3-thiotriphosphate)	affects binding, increases activity, increases expression	1
3’-O-(4-benzoyl)benzoyladenosine 5’-triphosphate	decreases reaction, increases reaction, increases secretion	1
beta-methylcholine	affects expression	1
jinfukang	affects cotreatment, decreases expression	1
4,4’-(carbonylbis(imino-3,1-phenylenecarbonylimino-3,1-(4-methylphenylene)carbonylimino))bis(1,3-xylene-alpha,alpha’-diphosphonic acid)	increases activity, increases expression, affects binding	1
Temozolomide	increases expression	1
Adenosine Triphosphate	affects binding, decreases expression, increases response to substance	1
Atrazine	decreases expression	1
Estradiol	increases expression	1
NAD	decreases reaction, increases reaction, increases secretion	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Genistein	increases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	decreases expression	1

ChEMBL screening assays

45 unique, capped per target: 31 functional, 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4880107	Binding	P2Y CEREP ligand profiling	Data for DCP probe A-079
CHEMBL1806221	Functional	Agonist activity at GFP tagged-human P2Y11 receptor expressed in human 1321N1 cells assessed as elevation in calcium level after 30 mins by fluorescence spectrophotometric analysis	Diadenosine 5’,5’’-(boranated)polyphosphonate analogues as selective nucleotide pyrophosphatase/phosphodiesterase inhibitors. — J Med Chem

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H356	1321N1/P2Y11	Cancer cell line	Male
CVCL_KY74	PathHunter CHO-K1 P2RY11 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZD94	1321N1-HA-P2Y11	Cancer cell line	Male
CVCL_ZI73	GeneBLAzer P2RY11-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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