P2RY6

Summary

P2RY6 (pyrimidinergic receptor P2Y6, HGNC:8543) is a protein-coding gene on chromosome 11q13.4, encoding P2Y purinoceptor 6 (Q15077). Receptor for extracellular UDP > UTP > ATP.

The product of this gene belongs to the family of P2 receptors, which is activated by extracellular nucleotides and subdivided into P2X ligand-gated ion channels and P2Y 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, which is a G-protein coupled receptor, is responsive to UDP, partially responsive to UTP and ADP, and not responsive to ATP. It is proposed that this receptor mediates inflammatory responses. Alternative splicing results in multiple transcript variants that encode different protein isoforms.

Source: NCBI Gene 5031 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 6 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001277204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8543
Approved symbol	P2RY6
Name	pyrimidinergic receptor P2Y6
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	P2Y6
Ensembl gene	ENSG00000171631
Ensembl biotype	protein_coding
OMIM	602451
Entrez	5031

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 27 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000349767, ENST00000393590, ENST00000393591, ENST00000393592, ENST00000535931, ENST00000536225, ENST00000538328, ENST00000540124, ENST00000540342, ENST00000542092, ENST00000544437, ENST00000618468, ENST00000679753, ENST00000680825, ENST00000680915, ENST00000680955, ENST00000859334, ENST00000859335, ENST00000859336, ENST00000859337, ENST00000859338, ENST00000859339, ENST00000960450, ENST00000960451, ENST00000960452, ENST00000960453, ENST00000960454, ENST00000960455

RefSeq mRNA: 8 — MANE Select: NM_001277204 NM_001277204, NM_001277205, NM_001277206, NM_001277207, NM_001277208, NM_176796, NM_176797, NM_176798

CCDS: CCDS8220

Canonical transcript exons

ENST00000540124 — 3 exons

Exon	Start	End
ENSE00001184996	73295730	73295815
ENSE00001301840	73296485	73298625
ENSE00002204750	73272338	73272466

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 88.54.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2206 / max 168.3081, expressed in 847 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115783	2.3825	355
115782	0.9681	259
115777	0.8616	274
115787	0.6339	229
115786	0.1210	48
115780	0.0673	32
115778	0.0506	26
115781	0.0413	18
115784	0.0396	21
115785	0.0303	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	88.54	gold quality
spleen	UBERON:0002106	87.21	gold quality
type B pancreatic cell	CL:0000169	84.70	gold quality
placenta	UBERON:0001987	84.61	gold quality
olfactory bulb	UBERON:0002264	84.36	gold quality
mucosa of urinary bladder	UBERON:0001259	81.63	gold quality
triceps brachii	UBERON:0001509	80.16	gold quality
gluteal muscle	UBERON:0002000	79.91	gold quality
right coronary artery	UBERON:0001625	79.52	gold quality
decidua	UBERON:0002450	75.36	gold quality
left coronary artery	UBERON:0001626	75.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.90	gold quality
coronary artery	UBERON:0001621	74.60	gold quality
vermiform appendix	UBERON:0001154	73.94	gold quality
ileal mucosa	UBERON:0000331	73.71	silver quality
buccal mucosa cell	CL:0002336	73.46	gold quality
quadriceps femoris	UBERON:0001377	73.45	gold quality
vastus lateralis	UBERON:0001379	73.34	gold quality
adult mammalian kidney	UBERON:0000082	73.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.34	gold quality
thoracic aorta	UBERON:0001515	72.12	gold quality
secondary oocyte	CL:0000655	72.09	gold quality
ascending aorta	UBERON:0001496	72.09	gold quality
right lobe of thyroid gland	UBERON:0001119	72.08	gold quality
cervix epithelium	UBERON:0004801	71.96	gold quality
caecum	UBERON:0001153	71.58	gold quality
metanephros cortex	UBERON:0010533	71.57	gold quality
jejunal mucosa	UBERON:0000399	71.27	silver quality
oocyte	CL:0000023	71.22	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.21	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	802.93
E-HCAD-36	yes	333.80
E-HCAD-13	yes	22.85
E-MTAB-8142	yes	18.23
E-MTAB-9467	yes	17.56
E-HCAD-1	yes	13.78
E-MTAB-9801	yes	8.14
E-CURD-88	yes	4.21
E-ANND-3	yes	2.98
E-MTAB-3929	no	175.56
E-MTAB-6379	no	4.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting P2RY6, 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-4283	100.00	66.42	2097
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-193A-5P	95.70	65.33	613

Literature-anchored findings (GeneRIF, showing 40)

• expression profile in human peripheral tissues and brain regions using PCR (PMID:11690642)
• hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation (PMID:12464620)
• P2Y(6) receptors interact rapidly with the TNF alpha-related intracellular signals to prevent apoptotic cell death. (PMID:12623123)
• Adenine and uracil nucleotides differentially activate this receptor, which regulates the proliferation of lung cancer cells (PMID:12691958)
• P2Y6 receptors highly responsive to UDP are endogenously expressed in human neuroblastoma SK-N-BE(2)C cells and they are involved in modulation of phospholipase C-coupled receptor-mediated Ca2+ mobilization by depleting the IP3-sensitive Ca2+ stores (PMID:12716436)
• findings expand the pro-inflammatory biology of UDP mediated by the P2Y6 receptor (PMID:15796906)
• P2Y receptors revealed that the P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating human neutrophil peptides-induced IL-8 production. (PMID:16322472)
• inotropic effects of UDP, mediated by P2Y6 receptors (PMID:16543499)
• on/off effect of IL-13 on P2Y(6)-induced Cl-secretion may help to identify the molecular determinants responsible for the CaCC channel activity (PMID:17762175)
• modulation of human cavernosal smooth muscle relaxation can be achieved by activation of the P2Y6 receptor via non-neuronal and non-NO-dependent mechanisms, reinforcing the possible involvement of purinergic signalling in the erectile process (PMID:17971163)
• P2Y6 receptor expression is increased by the stress-associated inflammatory response of Caco-2 intestinal epithelial cells. (PMID:18250478)
• These results indicate that activation of Galpha(12/13) in cardiomyocytes by the extracellular nucleotides-stimulated P2Y(6) receptor triggers fibrosis in pressure overload-induced cardiac fibrosis (PMID:19008857)
• P2Y agonists stimulate Ca(2+)-dependent Cl(-) secretion across human bronchial epithelia and that the cAMP/PKA pathway regulates apical but not basolateral P2Y(6) receptor-coupled ion transport in human bronchial epithelia (PMID:19011163)
• Human mast cells express uridine diphosphate-selective P2Y6 receptors that cooperate with type 1 cysteinyl-leukotriene receptors to promote cell survival and chemokine generation by a pathway involving reciprocal ligand-mediated cross-talk. (PMID:19124756)
• Extracellular nucleotides, via P2Y2 and P2Y6 receptors, regulate neutrophil migration by controlling TLR2-induced IL-8 release from human monocytes. (PMID:19735076)
• human microvascular endothelia exposed to inflammatory stimuli, followed by measurements of P2Y or P2X transcriptional responses, showed a selective induction of the P2Y(6) receptor (PMID:21173118)
• P2Y6 receptors and ADAM17 mediates the low-dose gamma-radiation-induced activation of EGFR. (PMID:21268712)
• activation of P2Y6 receptor mediates the UVB-radiation-induced activation of p38 MAPK and expression of COX-2 (PMID:21388279)
• P2Y6 receptor transgene is an important endogenous inhibitor of T cell function in mice with allergic pulmonary inflammation (PMID:21724990)
• Report role of ecto-NTPDases on UDP-sensitive P2Y(6) receptor activation during osteogenic differentiation of primary bone marrow stromal cells from postmenopausal women. (PMID:21898410)
• P2Y(6) receptor signaling pathway may be a potential therapeutic target for MSU-associated inflammatory diseases, such as tophaceous gout. (PMID:22102722)
• Results indicate involvement of P2Y purinoceptors P2Y(1) and P2Y(6) receptors in ADP- and UDP-stimulated proliferation. (PMID:22249129)
• no obvious correlation was found between the expression of P2Y6 and breast cancer cell proliferation (PMID:22558990)
• Data indicate that after P2Y6 receptor stimulation both phospholipase D (PLD) and DGKzeta enzymes are responsible for producing phosphatidic acid (PA). (PMID:23723068)
• nucleotides released during the airway inflammatory processes will activate P2Y6 receptors, which will lead to further release of inflammatory cytokines. (PMID:25243587)
• high millimolar concentrations of ATP increased IL-8 and MCP-1 release by the glioma cells stimulated with suboptimal LPS concentration which were blocked by P2X7 and P2Y6 antagonists (PMID:25445541)
• data demonstrate that HNP-1 induces IL-8 production not only through P2Y6, but also through additional P2 receptors via an ERK1/2-dependent mechanism in intestinal epithelial cells. (PMID:25816245)
• Expression levels of P2Y6 receptor were higher in Parkinson’s disease patients compared to healthy controls. (PMID:28219441)
• Rescuing miR-185 expression to inhibit P2Y6 may represent a therapeutic strategy against human aortic vascular smooth muscle cells dysfunction and hypertension. (PMID:28277742)
• UDP/P2Y6 receptor signaling is involved in the regulation of IgE-dependent degranulation in basophils, which might stimulate the P2Y6 receptor via the autocrine secretion of UTP. Thus, this receptor represents a potential target to regulate IgE-dependent degranulation in basophils during allergic diseases. (PMID:28318884)
• These data suggest that, without infection, inactivated-H5N1 induces mRNA expression of IL-6 and CXCL8 by a mechanism, or mechanisms, requiring interaction between viral hemagglutinin and alpha-2,3 sialic acid receptors at the cell membrane of host cells, and involves activation of P2Y6 purinergic receptors. (PMID:28494003)
• Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6. (PMID:28539604)
• The present study shows that sustained activation of P2Y6R may contribute to intestinal tumorigenesis by blocking the apoptotic process and by contributing to chemoresistance, a substantial concern in the treatment of patients with CRC. (PMID:29454075)
• The expression of the P2Y6 receptor is regulated at the transcriptional level by p53. (PMID:32037085)
• Investigating the associations of mucosal P2Y6 receptor expression and urinary ATP and ADP concentrations, with symptoms of overactive bladder. (PMID:32049380)
• The P2Y6 receptor signals through Galphaq /Ca(2+) /PKCalpha and Galpha13 /ROCK pathways to drive the formation of membrane protrusions and dictate cell migration. (PMID:32420639)
• Purinergic Receptor P2Y6 Is a Negative Regulator of NK Cell Maturation and Function. (PMID:34426542)
• P2Y6 receptor-dependent microglial phagocytosis of synapses mediates synaptic and memory loss in aging. (PMID:36565471)
• Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis. (PMID:37545227)
• Immunological role and clinical prognostic significance of P2RY6 in lung adenocarcinoma: a multi-omics studies and single-cell sequencing analysis. (PMID:37880703)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	P2ry6	ENSMUSG00000048779
rattus_norvegicus	P2ry6	ENSRNOG00000019270

Paralogs (15): GPR31 (ENSG00000120436), GPR42 (ENSG00000126251), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), OXGR1 (ENSG00000165621), P2RY1 (ENSG00000169860), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), HCAR2 (ENSG00000182782), FFAR3 (ENSG00000185897), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829), HCAR3 (ENSG00000255398)

Protein

Protein identifiers

P2Y purinoceptor 6 — Q15077 (reviewed: Q15077)

All UniProt accessions (5): A0A7P0TA46, Q15077, F5GX90, F5GYF3, F5H7H9

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for extracellular UDP > UTP > ATP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.

Subcellular location. Cell membrane.

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

RefSeq proteins (8): NP_001264133, NP_001264134, NP_001264135, NP_001264136, NP_001264137, NP_789766, NP_789767, NP_789768 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001973	P2Y6_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (19 total): topological domain 8, transmembrane region 7, chain 1, glycosylation site 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15077-F1	85.78	0.55

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): 99–177

Glycosylation sites (1): 5

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 253 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_G_PROTEIN_COUPLED_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_PROSTAGLANDIN_E, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, REACTOME_P2Y_RECEPTORS, GOBP_CELLULAR_RESPONSE_TO_PROSTAGLANDIN_STIMULUS, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (14): phagocytosis (GO:0006909), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), transepithelial chloride transport (GO:0030321), positive regulation of inositol trisphosphate biosynthetic process (GO:0032962), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to prostaglandin E stimulus (GO:0071380), cellular response to purine-containing compound (GO:0071415), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), cellular response to pyrimidine ribonucleotide (GO:1905835), signal transduction (GO:0007165), G protein-coupled purinergic nucleotide receptor signaling pathway (GO:0035589), cellular response to oxygen-containing compound (GO:1901701)

GO Molecular Function (6): G protein-coupled ADP receptor activity (GO:0001621), G protein-coupled receptor activity (GO:0004930), G protein-coupled UDP receptor activity (GO:0045029), G protein-coupled UTP receptor activity (GO:0045030), protein binding (GO:0005515), G protein-coupled purinergic nucleotide receptor activity (GO:0045028)

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	1
Nucleotide-like (purinergic) receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	2
G protein-coupled receptor signaling pathway	2
G protein-coupled pyrimidinergic nucleotide receptor activity	2
endocytosis	1
signal transduction	1
phospholipase C activator activity	1
chloride transport	1
transepithelial transport	1
inositol trisphosphate biosynthetic process	1
regulation of inositol trisphosphate biosynthetic process	1
positive regulation of inositol phosphate biosynthetic process	1
release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol	1
positive regulation of calcium ion transmembrane transport	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
response to prostaglandin E	1
cellular response to prostaglandin stimulus	1
cellular response to alcohol	1
cellular response to ketone	1
response to purine-containing compound	1
positive regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to pyrimidine ribonucleotide	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
cellular response to chemical stimulus	1
response to oxygen-containing compound	1
ADP binding	1
G protein-coupled purinergic nucleotide receptor activity	1
transmembrane signaling receptor activity	1
binding	1

Protein interactions and networks

STRING

816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
P2RY6	P2RX2	Q9UBL9	873
P2RY6	P2RX1	P51575	867
P2RY6	P2RX3	P56373	767
P2RY6	P2RX5	Q93086	763
P2RY6	P2RX4	Q99571	763
P2RY6	P2RX6	O15547	756
P2RY6	P2RX7	Q99572	705
P2RY6	GNAQ	P50148	671
P2RY6	P2RY2	P41231	611
P2RY6	ENTPD8	Q5MY95	610
P2RY6	ENTPD1	P49961	601
P2RY6	ENTPD3	O75355	594
P2RY6	P2RY12	Q9H244	566
P2RY6	CX3CL1	P78423	559
P2RY6	P2RY11	Q96G91	559

IntAct

56 interactions, top by confidence:

A	B	Type	Score
PLSCR1	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
P2RY6		psi-mi:“MI:0915”(physical association)	0.560
P2RY6	PLSCR1	psi-mi:“MI:0915”(physical association)	0.560
P2RY6	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
P2RY6	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
P2RY6	MCFD2	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
P2RY6	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
GRN	P2RY6	psi-mi:“MI:0915”(physical association)	0.560
P2RY6	WFS1	psi-mi:“MI:0915”(physical association)	0.560
CSE1L	P2RY6	psi-mi:“MI:0915”(physical association)	0.500
KPNB1	P2RY6	psi-mi:“MI:0915”(physical association)	0.500
P2RY6	CFTR	psi-mi:“MI:0915”(physical association)	0.370
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
P2RY6		psi-mi:“MI:0914”(association)	0.350

BioGRID (386): PLSCR1 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), PTPRJ (Negative Genetic), TPSAB1 (Negative Genetic), P2RY6 (Negative Genetic), P2RY6 (Negative Genetic), P2RY6 (Positive Genetic), P2RY6 (Positive Genetic), P2RY6 (Positive Genetic), ACADM (Affinity Capture-MS), ADCK4 (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), ALDH3A2 (Affinity Capture-MS), ALG5 (Affinity Capture-MS)

ESM2 similar proteins: A7YY44, B2GV46, O14843, O15529, O15552, O35811, O46685, O88855, O93361, P34996, P35383, P41231, P41232, P46093, P47900, P48042, P49650, P49651, P49652, P50132, P51582, P55085, P55086, P58825, P58826, P59902, Q09QM4, Q13304, Q15077, Q15743, Q1JQB3, Q2HJA4, Q3UFD7, Q4KLH9, Q5YA25, Q63371, Q63645, Q6IYF8, Q6NS65, Q6Y1R5

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, B2GV46, B5X337, D4A7K7, E7FEL0, E9QJ73, F8VQN3, O00270, O08726, O08858, O14842, O14843, O15529, O42179, O43603, O46685, O60755, O77408, O88410, O88626, O88634, O88853, P21109, P23944, P25024, P25025, P35344, P35383, P35414, P41231, P41232, P46092, P46093, P49652, P49682, P49683, P50132, P51675, P51679

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
P2RY6	“up-regulates activity”	GNAS	binding
P2RY6	“up-regulates activity”	GNAL	binding
P2RY6	“up-regulates activity”	GNAO1	binding
P2RY6	“up-regulates activity”	GNAZ	binding
P2RY6	“up-regulates activity”	GNA15	binding
P2RY6	“up-regulates activity”	GNA12	binding
P2RY6	“up-regulates activity”	GNA13	binding
UDP(3-)	“up-regulates activity”	P2RY6	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	8	27.9×	8e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

574 predictions. Top by Δscore:

Variant	Effect	Δscore
11:73264646:GCAG:G	donor_gain	1.0000
11:73264648:AGG:A	donor_loss	1.0000
11:73264649:GGTAA:G	donor_loss	1.0000
11:73264650:G:GG	donor_gain	1.0000
11:73264650:G:T	donor_loss	1.0000
11:73264651:T:G	donor_loss	1.0000
11:73277968:GC:G	donor_gain	0.9900
11:73296480:CCCA:C	acceptor_loss	0.9900
11:73296480:CCCAG:C	acceptor_gain	0.9900
11:73296481:CCAGC:C	acceptor_gain	0.9900
11:73296482:CA:C	acceptor_loss	0.9900
11:73296482:CAGCC:C	acceptor_gain	0.9900
11:73296483:A:AG	acceptor_gain	0.9900
11:73296483:AG:A	acceptor_loss	0.9900
11:73296484:G:GA	acceptor_gain	0.9900
11:73296484:GC:G	acceptor_gain	0.9900
11:73296484:GCC:G	acceptor_gain	0.9900
11:73296484:GCCT:G	acceptor_gain	0.9900
11:73296484:GCCTC:G	acceptor_gain	0.9900
11:73296479:TCCCA:T	acceptor_gain	0.9800
11:73296483:AGC:A	acceptor_gain	0.9800
11:73296484:G:C	acceptor_gain	0.9800
11:73277969:C:G	donor_gain	0.9700
11:73295805:G:GG	donor_gain	0.9700
11:73264649:GGTA:G	donor_gain	0.9600
11:73295789:A:G	donor_gain	0.9600
11:73295786:GAGA:G	donor_gain	0.9500
11:73264648:AGGT:A	donor_gain	0.9400
11:73264650:GTA:G	donor_gain	0.9400
11:73296474:T:A	acceptor_loss	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000018897 (11:73288287 C>T), RS1000268452 (11:73266449 A>G), RS1000330586 (11:73298849 C>A,T), RS1000344145 (11:73266663 C>T), RS1000371566 (11:73281638 G>A), RS1000498236 (11:73271037 C>T), RS1000827716 (11:73275957 G>A), RS1000980545 (11:73275919 T>C), RS1000996514 (11:73270911 C>A), RS1001083080 (11:73265318 A>G), RS1001223917 (11:73298124 C>G,T), RS1001229904 (11:73281094 G>A), RS1001254982 (11:73282163 A>C), RS1001304333 (11:73279873 C>G), RS1001369755 (11:73289384 A>C)

Disease associations

OMIM: gene MIM:602451 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_243	Refractive error	1.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524011 (PROTEIN FAMILY), CHEMBL4714 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 55,583 (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
CHEMBL1767408	DIQUAFOSOL TETRASODIUM	4	341
CHEMBL221326	DIQUAFOSOL	4	413
CHEMBL265502	SURAMIN	3	36,848
CHEMBL336296	URIDINE TRIPHOSPHATE	3	17,782
CHEMBL507282	DENUFOSOL	3	199

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — P2Y receptors

Most potent curated ligand interactions (21 total), top 21:

Ligand	Action	Affinity	Parameter
Rp-5-OMe-UDPαB	Agonist	8.1	pEC50
MRS2957	Agonist	7.9	pEC50
MRS2693	Full agonist	7.82	pEC50
MRS4162-BODIPY conjugate	Agonist	7.64	pEC50
UDP-β-S	Full agonist	7.55	pEC50
MRS2578	Antagonist	7.4	pIC50
3-phenacyl-UDP	Full agonist	7.2	pEC50
MRS2567	Antagonist	6.9	pIC50
INS48823	Full agonist	6.9	pEC50
Up3U	Full agonist	6.7	pEC50
UDP	Full agonist	6.5	pEC50
MRS2782	Full agonist	6.18	pEC50
5BrUTP	Partial agonist	6.1	pEC50
reactive blue-2	Antagonist	6.0	pKB
MRS4841	Antagonist	5.52	pIC50
TIM-38	Antagonist	5.37	pIC50
UTP	Partial agonist	5.2	pEC50
ADP	Partial agonist	4.5	pEC50
2MeSATP	Partial agonist	4.0	pEC50
PPADS	Antagonist	4.0	pKB
suramin	Antagonist	4.0	pKB

ChEMBL bioactivities

361 potent at pChembl≥5 of 390 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.23	IC50	5.914	nM	CHEMBL5431885
8.10	EC50	8	nM	CHEMBL2086761
8.05	EC50	9	nM	CHEMBL3220052
7.92	EC50	12	nM	CHEMBL1198754
7.92	EC50	12	nM	CHEMBL4279296
7.92	EC50	12	nM	CHEMBL1083256
7.90	IC50	12.59	nM	CHEMBL5436258
7.89	EC50	13	nM	CHEMBL590494
7.89	EC50	13	nM	URIDINE_DIPHOSPHATE
7.82	EC50	15	nM	URIDINE_DIPHOSPHATE
7.82	EC50	15	nM	CHEMBL1161882
7.82	IC50	15.24	nM	CHEMBL5439747
7.82	EC50	15	nM	CHEMBL590494
7.72	EC50	19	nM	CHEMBL3220047
7.71	IC50	19.6	nM	CHEMBL6173334
7.64	EC50	23	nM	CHEMBL3261378
7.63	IC50	23.42	nM	CHEMBL1321988
7.58	EC50	26	nM	CHEMBL1198872
7.58	IC50	26.5	nM	CHEMBL1443161
7.57	IC50	26.7	nM	CHEMBL6160847
7.56	IC50	27.47	nM	CHEMBL1321988
7.55	EC50	28	nM	CHEMBL2086770
7.53	IC50	29.6	nM	CHEMBL6160995
7.51	IC50	30.81	nM	CHEMBL5417339
7.50	EC50	32	nM	CHEMBL3220048
7.46	IC50	34.6	nM	CHEMBL1438995
7.43	IC50	37	nM	CHEMBL1321988
7.41	EC50	39	nM	CHEMBL3220046
7.40	IC50	39.8	nM	CHEMBL6165793
7.39	EC50	41	nM	CHEMBL3220050
7.38	EC50	42	nM	URIDINE_DIPHOSPHATE
7.38	EC50	41.6	nM	CHEMBL4295086
7.38	IC50	41.5	nM	CHEMBL6163952
7.38	EC50	42	nM	CHEMBL567321
7.38	EC50	42	nM	CHEMBL1086489
7.37	IC50	42.5	nM	CHEMBL5418022
7.34	IC50	45.72	nM	CHEMBL5406215
7.33	EC50	47	nM	URIDINE_DIPHOSPHATE
7.33	EC50	47	nM	CHEMBL602452
7.32	EC50	48	nM	URIDINE_DIPHOSPHATE
7.31	EC50	49.1	nM	CHEMBL4287835
7.31	EC50	49.1	nM	CHEMBL4851033
7.31	IC50	49.21	nM	CHEMBL5437857
7.28	IC50	52.8	nM	CHEMBL6164050
7.27	IC50	53.7	nM	CHEMBL6145737
7.26	IC50	54.6	nM	CHEMBL6171156
7.22	EC50	60	nM	CHEMBL2086765
7.22	EC50	60	nM	CHEMBL1161875
7.20	EC50	63	nM	CHEMBL1083257
7.19	IC50	64.13	nM	CHEMBL5407949

PubChem BioAssay actives

331 with measured affinity, of 799 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
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-6-chloro-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0059	uM
70688974	682415: Agonist activity at human GFP-tagged P2Y6 receptor expressed in human 1321N1 cells assessed as intracellular calcium mobilization by fura2/AM-based fluorescence spectrophotometry	ec50	0.0080	uM
2-(3-amino-6-imino-4,5-disulfoxanthen-9-yl)-5-[6-[4-[4-[3-[[[1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[[hydroxy(phosphonooxy)phosphoryl]oxymethyl]oxolan-2-yl]-2-oxopyrimidin-4-yl]amino]oxymethyl]phenyl]but-3-ynyl]triazol-1-yl]hexylcarbamoyl]benzoic acid;N,N-diethylethanamine	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.0090	uM
bis(N,N-diethylethanamine);[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(methoxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate	1416841: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as induction of PLC	ec50	0.0120	uM
[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(methoxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.0120	uM
N,N-diethylethanamine;[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(methoxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] [[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate	484784: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells assessed as [3H]inositol phosphate production by scintillation proximity assay	ec50	0.0120	uM
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-6-nitro-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0126	uM
[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate	460812: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as calcium elevation by fura2/AM assay	ec50	0.0130	uM
[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	271163: Agonist activity at human recombinant P2Y6 receptor expressed in 1321N1 cells assessed as PLC-mediated [3H]IP production	ec50	0.0130	uM
azane;[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-iodo-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate	271163: Agonist activity at human recombinant P2Y6 receptor expressed in 1321N1 cells assessed as PLC-mediated [3H]IP production	ec50	0.0150	uM
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-6-(trifluoromethyl)-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0152	uM
[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-[(3-iodophenyl)methoxyamino]-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl phosphono hydrogen phosphate	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.0190	uM
[[(2R,3S,4R,5R)-5-[4-[3-[4-[2-[2-[1-[3-[6-[[2-[4-[(E)-2-(2,2-difluoro-12-thiophen-2-yl-3-aza-1-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-1(12),4,6,8,10-pentaen-4-yl)ethenyl]phenoxy]acetyl]amino]hexanoylamino]propyl]triazol-4-yl]ethylamino]-2-oxoethoxy]phenyl]propoxyamino]-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1140091: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as stimulation of [3H]inositol phosphate accumulation by liquid scintillation counting	ec50	0.0230	uM
1-(3-isothiocyanatophenyl)-3-[4-[(3-isothiocyanatophenyl)carbamothioylamino]butyl]thiourea	2085547: Inhibition of P2Y6R (unknown origin) expressed in HEK293 cells assessed as decrease in IP3 reduction	ic50	0.0234	uM
[(2R,3S,4R,5R)-3,4-dihydroxy-5-[2-oxo-4-(phenylmethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methyl phosphono hydrogen phosphate	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.0260	uM
dihydroxyphosphinothioyl [(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	682412: Agonist activity at human P2Y6 receptor	ec50	0.0280	uM
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-1,3-benzoxazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0308	uM
[(2R,3S,4R,5R)-5-[4-[(4-bromophenyl)methoxyamino]-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.0320	uM
[(2R,3S,4R,5R)-5-[4-[(3-bromophenyl)methoxyamino]-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.0390	uM
[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-[(4-nitrophenyl)methoxyamino]-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl phosphono hydrogen phosphate	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.0410	uM
bis(N,N-diethylethanamine);[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1764005: Agonist activity at human P2Y6R expressed in 1321N1 cells assessed as calcium mobilization measured by microplate reader method	ec50	0.0416	uM
[(1S,2R,3R,4S,5S)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxy-2-bicyclo[3.1.0]hexanyl]methyl phosphono hydrogen phosphate	444562: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells coexpressing phospholipase C-activating Gq protein assessed as [3H]inositol phosphate production	ec50	0.0420	uM
azane;[(1S,2R,3R,4S,5S)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxy-2-bicyclo[3.1.0]hexanyl]methyl phosphono hydrogen phosphate	484784: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells assessed as [3H]inositol phosphate production by scintillation proximity assay	ec50	0.0420	uM
2-(1-tert-butyl-5-phenylpyrazol-3-yl)-6-methyl-1,3-benzoxazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0425	uM
6-bromo-2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0457	uM
[(2R,3S,4R,5R)-5-(5-bromo-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydroxyphosphinothioyl hydrogen phosphate	460812: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as calcium elevation by fura2/AM assay	ec50	0.0470	uM
bis(N,N-diethylethanamine);[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate	1416840: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as induction of calcium mobilization by FLIPR method	ec50	0.0491	uM
bis(N,N-diethylethanamine);[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1764005: Agonist activity at human P2Y6R expressed in 1321N1 cells assessed as calcium mobilization measured by microplate reader method	ec50	0.0491	uM
2-(1-tert-butyl-5-phenylpyrazol-3-yl)-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0492	uM
azane;[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-oxo-2-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate	271163: Agonist activity at human recombinant P2Y6 receptor expressed in 1321N1 cells assessed as PLC-mediated [3H]IP production	ec50	0.0600	uM
70691080	682415: Agonist activity at human GFP-tagged P2Y6 receptor expressed in human 1321N1 cells assessed as intracellular calcium mobilization by fura2/AM-based fluorescence spectrophotometry	ec50	0.0600	uM
bis[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(methoxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate	484784: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells assessed as [3H]inositol phosphate production by scintillation proximity assay	ec50	0.0630	uM
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-6-fluoro-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0641	uM
[(2R,3S,4R,5R)-5-(2,4-dioxo-3-phenacylpyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	272722: Agonist activity at human P2Y6 receptor expressed in 1321N1 cells assessed as IP accumulation by SPA	ec50	0.0700	uM
[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(methoxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl phosphono hydrogen phosphate;hydrochloride	444562: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells coexpressing phospholipase C-activating Gq protein assessed as [3H]inositol phosphate production	ec50	0.0700	uM
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-6-methyl-1,3-benzoxazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0729	uM
2-(1-tert-butyl-5-phenylpyrazol-3-yl)-6-methyl-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0779	uM
[(2R,3S,4R,5R)-3,4-dihydroxy-5-(2-oxo-4-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate	271163: Agonist activity at human recombinant P2Y6 receptor expressed in 1321N1 cells assessed as PLC-mediated [3H]IP production	ec50	0.0800	uM
[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-methoxy-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl phosphono hydrogen phosphate	460812: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as calcium elevation by fura2/AM assay	ec50	0.0800	uM
N,N-diethylethanamine;[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(methoxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	484784: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells assessed as [3H]inositol phosphate production by scintillation proximity assay	ec50	0.0800	uM
2-(5-phenyl-1-propan-2-ylpyrazol-3-yl)-1,3-benzothiazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0878	uM
[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-[3-(4-iodophenyl)propoxyamino]-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1140091: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as stimulation of [3H]inositol phosphate accumulation by liquid scintillation counting	ec50	0.0900	uM
[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(3-naphthalen-2-ylpropoxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1140091: Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells assessed as stimulation of [3H]inositol phosphate accumulation by liquid scintillation counting	ec50	0.0900	uM
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-4-chloro-1H-benzimidazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0935	uM
2-[1-tert-butyl-5-(furan-2-yl)pyrazol-3-yl]-4-methyl-1,3-benzoxazole	2031163: Antagonist activity at human P2Y6R expressed in HEK293 cells assessed as inhibition of UDP-induced IP3 production preincubated for 0.5 hrs followed by UDP stimulation and measured after 12 hrs by ELISA analysis	ic50	0.0942	uM
[[(2R,3S,4R,5R)-5-(5-chloro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid;bis(N,N-diethylethanamine)	1764005: Agonist activity at human P2Y6R expressed in 1321N1 cells assessed as calcium mobilization measured by microplate reader method	ec50	0.0970	uM
1-isothiocyanato-4-[2-(4-isothiocyanatophenyl)ethyl]benzene	1953757: Antagonist activity at human P2Y6	ic50	0.1000	uM
[(2R,3S,4R,5R)-5-[4-[(3-hexa-1,5-diynylphenyl)methoxyamino]-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1121982: Agonist activity at human recombinant P2Y6 receptor expressed in human 1321N1 cells using [3H]inositol as substrate assessed as [3H]inositol phosphate formation after 30 mins by liquid scintillation counting analysis	ec50	0.1000	uM
[[(2R,3S,4R,5R)-5-(5-bromo-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid;bis(N,N-diethylethanamine)	1764005: Agonist activity at human P2Y6R expressed in 1321N1 cells assessed as calcium mobilization measured by microplate reader method	ec50	0.1040	uM
[[[[(2R,3S,4R,5R)-5-(5-bromo-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]-dichloromethyl]phosphonic acid	272722: Agonist activity at human P2Y6 receptor expressed in 1321N1 cells assessed as IP accumulation by SPA	ec50	0.1200	uM

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
N,N’’-1,4-butanediylbis(N’-(3-isothiocyanatophenyl))thiourea	affects binding, decreases activity, decreases expression, decreases reaction, decreases response to substance (+1 more)	3
Cadmium	decreases expression, increases abundance, increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Hydrogen Peroxide	affects expression, decreases reaction, decreases response to substance, increases reaction	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	affects expression, affects cotreatment, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
TL8-506	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
quercitrin	decreases expression	1
sodium bichromate	decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, affects cotreatment	1
licochalcone B	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Adenosine Triphosphate	decreases reaction, decreases response to substance, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Allergens	increases expression	1
Arsenic	increases expression	1
Cisplatin	affects cotreatment, increases expression	1

ChEMBL screening assays

143 unique, capped per target: 91 functional, 52 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
CHEMBL1045263	Functional	Agonist activity at human P2Y6 receptor expressed in human 1321N1 cells coexpressing phospholipase C-activating Gq protein assessed as [3H]inositol phosphate production	Human P2Y(14) receptor agonists: truncation of the hexose moiety of uridine-5’-diphosphoglucose and its replacement with alkyl and aryl groups. — 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_H360	1321N1/P2Y6	Cancer cell line	Male
CVCL_KY77	PathHunter CHO-K1 P2RY6 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZD93	1321N1-HA-P2Y6	Cancer cell line	Male
CVCL_ZK60	GeneBLAzer P2RY6-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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