PTGIR

Summary

PTGIR (prostaglandin I2 receptor, HGNC:9602) is a protein-coding gene on chromosome 19q13.32, encoding Prostacyclin receptor (P43119). Receptor for prostacyclin (prostaglandin I2 or PGI2).

The protein encoded by this gene is a member of the G-protein coupled receptor family 1 and has been shown to be a receptor for prostacyclin. Prostacyclin, the major product of cyclooxygenase in macrovascular endothelium, elicits a potent vasodilation and inhibition of platelet aggregation through binding to this receptor.

Source: NCBI Gene 5739 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 74 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000960

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9602
Approved symbol	PTGIR
Name	prostaglandin I2 receptor
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	IP
Ensembl gene	ENSG00000160013
Ensembl biotype	protein_coding
OMIM	600022
Entrez	5739

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 retained_intron

ENST00000291294, ENST00000594275, ENST00000595460, ENST00000596260, ENST00000597185, ENST00000598865, ENST00000718329, ENST00000872951, ENST00000872952, ENST00000872953, ENST00000872954, ENST00000967894, ENST00000967895, ENST00000967896

RefSeq mRNA: 1 — MANE Select: NM_000960 NM_000960

CCDS: CCDS12686

Canonical transcript exons

ENST00000291294 — 3 exons

Exon	Start	End
ENSE00001134153	46620468	46621672
ENSE00001374265	46623458	46624237
ENSE00004034798	46624997	46625089

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 95.80.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2857 / max 169.7466, expressed in 830 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181655	5.2857	830

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ascending aorta	UBERON:0001496	95.80	gold quality
thoracic aorta	UBERON:0001515	95.76	gold quality
descending thoracic aorta	UBERON:0002345	95.66	gold quality
right coronary artery	UBERON:0001625	92.92	gold quality
aorta	UBERON:0000947	91.47	gold quality
left coronary artery	UBERON:0001626	90.27	gold quality
coronary artery	UBERON:0001621	89.85	gold quality
upper lobe of left lung	UBERON:0008952	88.79	gold quality
monocyte	CL:0000576	88.37	gold quality
tibial artery	UBERON:0007610	88.37	gold quality
popliteal artery	UBERON:0002250	88.35	gold quality
apex of heart	UBERON:0002098	87.97	gold quality
mononuclear cell	CL:0000842	87.92	gold quality
upper lobe of lung	UBERON:0008948	87.60	gold quality
leukocyte	CL:0000738	87.20	gold quality
right atrium auricular region	UBERON:0006631	87.07	gold quality
right lung	UBERON:0002167	86.84	gold quality
cardiac atrium	UBERON:0002081	85.42	gold quality
pericardium	UBERON:0002407	85.21	gold quality
vena cava	UBERON:0004087	83.86	silver quality
granulocyte	CL:0000094	83.11	gold quality
right lobe of thyroid gland	UBERON:0001119	82.76	gold quality
left lobe of thyroid gland	UBERON:0001120	81.82	gold quality
omental fat pad	UBERON:0010414	81.02	gold quality
peritoneum	UBERON:0002358	80.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.89	gold quality
heart	UBERON:0000948	80.75	gold quality
metanephros cortex	UBERON:0010533	80.64	gold quality
thyroid gland	UBERON:0002046	80.60	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	86.47
E-ANND-3	yes	4.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FLT1, POU2F1, SP1, SPI1

miRNA regulators (miRDB)

22 targeting PTGIR, 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-3119	99.92	71.34	2390
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4652-5P	96.46	64.22	553
HSA-MIR-4793-3P	94.87	65.85	896
HSA-MIR-6886-5P	91.08	63.10	105
HSA-MIR-10392-3P	88.79	61.83	122

Literature-anchored findings (GeneRIF, showing 40)

• Impaired receptor binding and activation associated with polymorphism (PMID:11854299)
• role in protein isoprenylation (PMID:11895442)
• Data show that prostacyclin receptor mediated increases in cAMP play a role in enhancing LPS/IFN-gamma-induced iNOS expression in human monocytes/macrophages and may contribute to the increased production of NO during peritonitis. (PMID:12119468)
• identification of a unique ligand-binding pocket by site-directed mutagenesis and molecular modeling (PMID:12446735)
• current state of knowledge of the prostacyclin receptor, its signaling and regulation, and its biological role in vivo [review] (PMID:12481546)
• activation-dependent internalization of this receptor (PMID:12664600)
• the presence of a free heavy chain IgG in the circulation from spinal cord-injured subjects blocked insulin receptor binding sites and also blocked the prostacyclin receptor interaction in platelets; insulin-induced NO synthesis was markedly impaired. (PMID:12850828)
• Iloprost stimulation (1 microM, 2 h) of IP prostanoid receptor expressed in HEK293 cells resulted in specific decrease of endogenous G(s)alpha protein in detergent-insensitive, caveolin-enriched, membrane domains (PMID:15053924)
• elucidated the molecular requirements for receptor activation within the region of the ligand-binding pocket, identifying transmembrane residues affecting potency (PMID:15248755)
• The -CSLC motif of the IP is a direct target for inhibition by the FTI SCH66336, and in the presence of strong farnesyltransferase inhibition, the IP does not undergo compensatory geranylgeranylation. (PMID:15469414)
• prostacyclin and thromboxane receptor dimerization facilitates thromboxane receptor-mediated cAMP generation (PMID:15471868)
• results demonstrate for the first time that prostacyclin receptor activation by cicaprost can lead to STAT1 and STAT3 phosphorylations via signaling pathways involving pertussis toxin-insensitive G proteins, ERK and JNK (PMID:15979846)
• The first intracellular loop of human prostacyclin receptor (IP) was proposed to be involved in signaling via its interaction with the Galphas protein. (PMID:16114876)
• PGI-IP interaction within glandular epithelial cells can promote the expression of proangiogenic genes in human endometrium via cross talk with the EGFR. (PMID:16373414)
• These data suggest that iloprost modulates VSMC phenotype via G(s) activation of the cAMP/PKA pathway. (PMID:16399867)
• AC6 overexpression in endothelial cells may have use as a means to enhance prostacyclin function and reduce endothelial barrier permeability. (PMID:16885208)
• results indicate that the three residues (E392-L394) of the Galphas protein predicted from NMR peptide studies, and the IP iLP1 and iLP3 play important roles in the Galphas-mediated IP receptor signaling in the cells. (PMID:16942748)
• analysis of roles of cysteine residues in human prostacyclin receptor structure and function (PMID:17015447)
• Three Arg-targeted changes at the same 212 position within the third cytoplasmic loop of the human prostacyclin (hIP) receptor were detected. (PMID:17481829)
• The charged residues and the presence of naturally occurring mutations in prostacyclin receptor have important implications in the rational design of prostacyclin agonists for treating cardiovascular disease. (PMID:17704830)
• Prostaglandin I(2) receptor (IP) was more specifically expressed in hair cuticle layer and outer root sheath (ORS) basal layer. (PMID:18005048)
• A profile of the residues in the second extracellular loop that are critical for ligand recognition of human prostacyclin receptor (PMID:18042246)
• IP-receptor agonists may limit the mitogenic actions of thrombin in human SMC by downregulating PAR-1 via modulation of cAMP-/PKA- and Rac1-dependent signaling pathways. (PMID:18162607)
• diminished prostacyclin receptor signaling may contribute, in part, to the underlying adverse cardiovascular outcomes observed with cyclooxygenase-2 inhibition. (PMID:18323528)
• A propensity of enhanced platelet activation in deep vein thrombosis patients with PTGIR polymorphisms V53V/S328S; A dysfunctional PTGIR polymorphism (R212C) associated with intimal hyperplasia. (PMID:18551041)
• Data suggest that expression of prostanoid receptors (prostaglandin E2 EP3-I, prostacyclin, and thromboxane A2 receptors) in vascular inflammation could influence cell responses dependent on the constitutive activation of ghrelin receptors. (PMID:18573679)
• Co-stimulation of G(s) and G(q) can result in the fine-tuning of STAT3 activation status, and this may provide the basis for cell type-specific responses following activation of hIP. (PMID:18755267)
• The prostacyclin receptor plays a central role in regulating its recycling following agonist activation by rab11 protein binding domain within its C-tail domain. (PMID:18832025)
• These data provide critical insights into the transcriptional regulation of the IP gene in human megakaryocytic and endothelial cells, identifying Sp1, PU.1 and Oct-1 as the critical factors involved in its basal regulation in humans. (PMID:19118563)
• The human IP gene is directly regulated by estrogen that largely occurs through an ERalpha-dependent transcriptional mechanism. (PMID:20070947)
• Observed induction of the PG receptors EP2 and IP in atherosclerotic femoral arteries in the arterial intima, medial layer, as well as the associated atherosclerotic plaque. (PMID:20357748)
• decreased maternal plasma levels in severe preeclamptic pregnant women (PMID:20482519)
• IP(R212C) exerts a dominant action on the wild-type IP and thromboxane receptor through dimerization. This likely contributes to accelerated cardiovascular disease in individuals carrying 1 copy of the variant allele. (PMID:20522800)
• of 18 non-synonymous mutations, all with frequencies less than 2% in our study cohort, eight of the 18 had defects in binding, activation, and/or protein stability/folding (PMID:21189259)
• study identified a novel 8 residue ER export motif within the functionally important alpha-H8 of the hIP. (PMID:21223948)
• Human prostacyclin receptor interacts with the PDZ adapter protein PDZK1; this interaction plays important role in endothelial cell migration and angiogenesis. (PMID:21653824)
• VDAC is the ATP conduit in the IP receptor-mediated signaling pathway in human erythrocytes. (PMID:22159995)
• Prostacyclin receptor-dependent inhibition of human erythroleukemia cell differentiation is STAT3-dependent (PMID:22336225)
• the IP receptor was expressed in blood vessels of renal cell carcinoma specimens, but not in glomerular vessels of normal renal tissue; findings suggest the IP receptor might maintain an angiogenic switch in the “on” state in tumor endothelial cells (TEC); suggest that the IP receptor is a TEC-specific marker and might be a useful therapeutic target (PMID:22380928)
• these data provide critical insights into the transcriptional regulation of the human prostacyclin receptor gene within the vasculature, including during megakaryocytic differentiation (PMID:22381139)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptgir	ENSDARG00000038278
mus_musculus	Ptgir	ENSMUSG00000043017
rattus_norvegicus	Ptgir	ENSRNOG00000016756

Paralogs (7): TBXA2R (ENSG00000006638), PTGER3 (ENSG00000050628), PTGFR (ENSG00000122420), PTGER2 (ENSG00000125384), PTGER1 (ENSG00000160951), PTGDR (ENSG00000168229), PTGER4 (ENSG00000171522)

Protein

Protein identifiers

Prostacyclin receptor — P43119 (reviewed: P43119)

Alternative names: Prostaglandin I2 receptor, Prostanoid IP receptor

All UniProt accessions (5): P43119, A0A0B4J2A7, M0QXV5, M0QZI2, M0QZW0

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.

Subunit / interactions. Interacts (non-isoprenylated C-terminus) with PDZK1.

Subcellular location. Cell membrane.

Post-translational modifications. Isoprenylation does not influence ligand binding but is required for efficient coupling to the effectors adenylyl cyclase and phospholipase C.

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

RefSeq proteins (1): NP_000951* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000370	Prostglndn_IP_rcpt	Family
IPR008365	Prostanoid_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (43 total): helix 10, topological domain 8, transmembrane region 7, strand 4, disulfide bond 2, sequence variant 2, turn 2, chain 1, propeptide 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1, glycosylation site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8X79	ELECTRON MICROSCOPY	2.41
8X7A	ELECTRON MICROSCOPY	2.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43119-F1	76.80	0.40

Antibody-complex structures (SAbDab): 2 — 8X79, 8X7A

Functional residue map

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

Post-translational modifications (2): 383, 383

Disulfide bonds (2): 5–165, 92–170

Glycosylation sites (1): 7

Mutagenesis-validated functional residues (1):

Position	Phenotype
383	abolishes isoprenylation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-391908	Prostanoid ligand receptors
R-HSA-392851	Prostacyclin signalling through prostacyclin receptor
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 219 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_92, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_INFLAMMATORY_RESPONSE, REACTOME_EICOSANOID_LIGAND_BINDING_RECEPTORS, MODULE_64, GOBP_MUSCLE_CELL_PROLIFERATION, CAGCTG_AP4_Q5, CCATCCA_MIR432, CEBPB_01, GOBP_CELL_CELL_SIGNALING, NFKB_Q6, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (10): inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), negative regulation of platelet-derived growth factor receptor signaling pathway (GO:0010642), response to lipopolysaccharide (GO:0032496), negative regulation of smooth muscle cell proliferation (GO:0048662), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), prostacyclin receptor activity (GO:0016501), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (3): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Eicosanoid ligand-binding receptors	1
Platelet homeostasis	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
cell communication	2
signaling	2
cellular anatomical structure	2
defense response	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
regulation of biological quality	1
negative regulation of signal transduction	1
regulation of platelet-derived growth factor receptor signaling pathway	1
platelet-derived growth factor receptor signaling pathway	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
negative regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
prostaglandin receptor activity	1
transmembrane signaling receptor activity	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGIR	PTGIS	Q16647	829
PTGIR	PTGS1	P23219	725
PTGIR	PTGS2	P35354	658
PTGIR	GNAS	Q5JWF2	577
PTGIR	ST6GALNAC5	Q9BVH7	542
PTGIR	PDE5A	O76074	519
PTGIR	PTGES	O14684	511
PTGIR	TBXAS1	P24557	507
PTGIR	TBXA2R	P21731	472
PTGIR	PDZK1	Q5T2W1	472
PTGIR	CELF2	O95319	469
PTGIR	EREG	O14944	447
PTGIR	PTGDR2	Q9Y5Y4	447
PTGIR	PTGES2	Q9H7Z7	442
PTGIR	HAS2	Q92819	437
PTGIR	CHCHD7	Q9BUK0	437

IntAct

120 interactions, top by confidence:

A	B	Type	Score
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
MAGI2	PTGIR	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	PTGIR	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
RADIL	PTGIR	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	PTGIR	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	GOPC	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
PTGIR	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (130): SLC12A6 (Affinity Capture-MS), SLC6A8 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), UGCG (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), FZD2 (Affinity Capture-MS), SLC30A1 (Affinity Capture-MS), ANO5 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), SLC15A4 (Affinity Capture-MS), SLC4A2 (Affinity Capture-MS), GLMN (Affinity Capture-MS), SLC9A1 (Affinity Capture-MS), PDXDC1 (Affinity Capture-MS), SLC12A7 (Affinity Capture-MS)

ESM2 similar proteins: A5D7K8, O35932, O95136, O95977, P21731, P30557, P30987, P34972, P34978, P34979, P34980, P35375, P35408, P37289, P43088, P43114, P43115, P43116, P43117, P43118, P43119, P43252, P43253, P46069, P47752, P47901, P47936, P50131, P52592, P56486, P70263, P70597, P79393, Q13258, Q28691, Q28905, Q5R949, Q62053, Q62928, Q8MJ08

Diamond homologs: A5D7K8, O35932, P34978, P43116, P43119, P43252, P43253, P70263, P79393, Q13258, Q62053, Q62928, Q9R261, Q9XT82, P32240, P35408, P43114, Q28691, Q8MJ08, Q95KZ0, O02662, P21731, P30557, P30987, P34979, P34980, P34995, P35375, P37289, P43088, P43115, P43117, P43118, P43141, P46069, P46626, P50131, P56486, P70597, Q28524

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	PTGIR	phosphorylation
PTGIR	“up-regulates activity”	GNAS	binding
PTGIR	“up-regulates activity”	GNAL	binding
PTGIR	“up-regulates activity”	GNAQ	binding
iloprost	“up-regulates activity”	PTGIR	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
Ras activation upon Ca2+ influx through NMDA receptor	5	54.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	52.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	52.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	48.8×	9e-13
Dopamine Neurotransmitter Release Cycle	5	47.7×	2e-06
Long-term potentiation	5	45.8×	2e-06
Neurexins and neuroligins	10	37.9×	7e-12
Protein-protein interactions at synapses	6	30.6×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	82.0×	2e-16
receptor clustering	7	56.0×	7e-09
protein localization to synapse	5	49.1×	3e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	44.5×	3e-08
cell-cell adhesion	10	13.0×	4e-07
protein-containing complex assembly	8	11.7×	2e-05
chemical synaptic transmission	7	6.9×	2e-03
protein transport	8	4.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

480 predictions. Top by Δscore:

Variant	Effect	Δscore
19:46623453:CTCA:C	donor_loss	1.0000
19:46623454:TCACC:T	donor_loss	1.0000
19:46623455:CA:C	donor_loss	1.0000
19:46623456:A:AC	donor_gain	1.0000
19:46623456:AC:A	donor_gain	1.0000
19:46623457:C:CC	donor_gain	1.0000
19:46623457:CC:C	donor_gain	1.0000
19:46621672:TC:T	acceptor_loss	0.9900
19:46623457:CCG:C	donor_gain	0.9900
19:46623457:CCGT:C	donor_gain	0.9900
19:46623457:CCGTG:C	donor_gain	0.9900
19:46625009:G:A	donor_gain	0.9900
19:46625019:T:A	donor_gain	0.9900
19:46621668:CGGAT:C	acceptor_gain	0.9800
19:46621673:C:CC	acceptor_gain	0.9800
19:46624233:CTGGG:C	acceptor_gain	0.9800
19:46624992:CGCAC:C	donor_loss	0.9800
19:46624993:GCA:G	donor_loss	0.9800
19:46624994:CA:C	donor_loss	0.9800
19:46624995:ACCT:A	donor_loss	0.9800
19:46624996:C:CG	donor_loss	0.9800
19:46624996:CCT:C	donor_gain	0.9800
19:46623451:GACTC:G	donor_loss	0.9700
19:46623452:ACTCA:A	donor_loss	0.9700
19:46624238:C:CC	acceptor_gain	0.9600
19:46625038:G:A	donor_gain	0.9500
19:46625048:G:A	donor_gain	0.9500
19:46621962:C:A	donor_gain	0.9400
19:46621671:AT:A	acceptor_gain	0.9300
19:46625000:T:A	donor_gain	0.9200

AlphaMissense

2456 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:46624022:G:C	S68R	0.997
19:46624022:G:T	S68R	0.997
19:46624024:T:G	S68R	0.997
19:46621573:A:G	W290R	0.994
19:46621573:A:T	W290R	0.994
19:46623719:C:A	W169C	0.994
19:46623719:C:G	W169C	0.994
19:46623722:G:C	S168R	0.993
19:46623722:G:T	S168R	0.993
19:46623724:T:G	S168R	0.993
19:46624079:G:C	F49L	0.993
19:46624079:G:T	F49L	0.993
19:46624081:A:G	F49L	0.993
19:46623716:G:C	C170W	0.991
19:46623721:A:G	W169R	0.991
19:46623721:A:T	W169R	0.991
19:46623987:G:A	S80F	0.991
19:46624047:T:A	D60V	0.991
19:46624050:G:A	T59I	0.991
19:46624046:G:C	D60E	0.990
19:46624046:G:T	D60E	0.990
19:46624166:G:C	S20R	0.990
19:46624166:G:T	S20R	0.990
19:46624168:T:G	S20R	0.990
19:46623718:A:G	C170R	0.989
19:46624047:T:G	D60A	0.989
19:46621565:G:C	F292L	0.988
19:46621565:G:T	F292L	0.988
19:46621567:A:G	F292L	0.988
19:46623475:A:G	C251R	0.988

dbSNP variants (sampled 300 via entrez): RS1000026162 (19:46615647 G>A), RS1000122525 (19:46616356 C>A), RS1000168088 (19:46623079 T>G), RS1000368838 (19:46615375 G>T), RS1000622010 (19:46626234 G>A), RS1000702413 (19:46616351 T>A), RS1000768786 (19:46621601 G>A,C), RS1000784657 (19:46621092 G>A), RS1001105080 (19:46626686 G>A), RS1001410895 (19:46626453 C>T), RS1001885094 (19:46615046 A>G), RS1002103511 (19:46610251 G>A,C), RS1002127076 (19:46624500 G>C), RS1002328840 (19:46620425 G>T), RS1002592170 (19:46626141 C>A)

Disease associations

OMIM: gene MIM:600022 | disease phenotypes: MIM:192500

GenCC curated gene-disease

Mondo (1): long QT syndrome 1 (MONDO:0100316)

Orphanet (2): Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004132_48	Crohn’s disease	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1995 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 32,923 (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
CHEMBL1237119	TREPROSTINIL	4	766
CHEMBL238804	SELEXIPAG	4	1,018
CHEMBL426559	LAROPIPRANT	4	541
CHEMBL494	ILOPROST	4	234
CHEMBL495	ALPROSTADIL	4	13,450
CHEMBL548	DINOPROSTONE	4	14,939
CHEMBL3301604	RALINEPAG	3	260
CHEMBL560993	TIMAPIPRANT	3	285
CHEMBL239226	LASELIPAG	2	314
CHEMBL271896	BUTAPROST	2	1,116

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1126510	Toxicity	3	aspirin	Asthma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1126510	PTGIR	3	1.50	1	aspirin

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Prostanoid receptors

Most potent curated ligand interactions (26 total), top 25:

Ligand	Action	Affinity	Parameter
BAY-73-1449	Antagonist	10.0	pIC50
[3H]iloprost	Full agonist	9.0	pKd
CAY10441	Antagonist	8.7	pKi
AFP-07	Full agonist	8.5	pIC50
TEI-9063	Full agonist	8.5	pIC50
FK-788	Full agonist	8.05	pKi
iloprost	Full agonist	8.0	pKi
BMY 45778	Full agonist	8.0	pIC50
esuberaprost	Agonist	7.89	pKd
PGI2	Agonist	7.8	pKi
cicaprost	Full agonist	7.8	pKi
isocarbacyclin	Full agonist	7.8	pKi
MRE-269	Full agonist	7.7	pKi
treprostinil	Full agonist	7.49	pKi
beraprost	Agonist	7.41	pKi
ONO-1301	Full agonist	7.3	pKi
FR181157	Full agonist	7.27	pKi
taprostene	Full agonist	6.9	pIC50
RO3244794	Antagonist	6.9	pKi
PGE1	Full agonist	6.82	pKi
TG6-129	Antagonist	6.7	pKB
carbacyclin	Full agonist	6.6	pKi
selexipag	Agonist	6.59	pKi
EP 157	Full agonist	5.69	pIC50
butaprost (free acid form)	Full agonist	4.3	pKi

Binding affinities (BindingDB)

38 measured of 56 human assays (57 total across all organisms); most potent 38 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_5311503	KI	0.3 nM
NSC_3080928	KI	0.4 nM
CAS_41598-07-6	KI	1.7 nM
2-[[4-[[5-(2-hydroxyethylsulfanyl)-4-(3-methoxyphenyl)-3-phenylpyrazol-1-yl]methyl]cyclohexyl]methoxy]acetic acid	EC50	2 nM	US-10214518
2-[[4-[[5-ethylsulfanyl-4-(2-fluoro-3-methoxyphenyl)-3-phenylpyrazol-1-yl]methyl]cyclohexyl]methoxy]acetic acid	EC50	7 nM	US-10214518
(2S)-2-[(5-{[4-(3-acetamidophenyl)phenyl]methyl}-1,3-oxazol-4-yl)formamido]-3-phenylpropanoic acid	EC50	16 nM
2-[[4-[[5-(cyanomethylsulfanyl)-3,4-diphenylpyrazol-1-yl]methyl]cyclohexyl]methoxy]acetic acid	IC50	20 nM	US-10214518
2-[[4-[[5-methylsulfanyl-4-(5-methylthiophen-2-yl)-3-phenylpyrazol-1-yl]methyl]cyclohexyl]methoxy]acetic acid	IC50	28 nM	US-10214518
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-[(2R)-2-phenylpropyl]-1,3-oxazole-4-carboxamide	EC50	51 nM
N-benzyl-5-{[4-(3-acetamidophenyl)phenyl]methyl}-1,3-oxazole-4-carboxamide	EC50	66 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-(2-phenylpropyl)-1,3-oxazole-4-carboxamide	IC50	77 nM
PGI2	KI	132 nM
PGE1	KI	137 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-(2-phenylethyl)-1,3-oxazole-4-carboxamide	EC50	138 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-(1-phenylethyl)-1,3-oxazole-4-carboxamide	EC50	278 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-[(2S)-2-phenylpropyl]-1,3-oxazole-4-carboxamide	EC50	296 nM
CAS_19313-28-1	KI	315 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-[(1S,2R)-2-phenylcyclopropyl]-1,3-oxazole-4-carboxamide	IC50	331 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-[2-(pyridin-4-yl)ethyl]-1,3-oxazole-4-carboxamide	EC50	476 nM
CAS_54751	KI	697 nM
(E)-7-((1R,2R,3R)-3-hydroxy-2-((S,E)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoic acid	KI	735 nM
8-ISO PROSTAGLANDIN E1	KI	735 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-[2-(pyridin-3-yl)ethyl]-1,3-oxazole-4-carboxamide	EC50	741 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-phenyl-1,3-oxazole-4-carboxamide	EC50	828 nM
(2R)-2-[(5-{[4-(3-acetamidophenyl)phenyl]methyl}-1,3-oxazol-4-yl)formamido]-3-phenylpropanoic acid	EC50	831 nM
(Z)-7-[(1R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-oct-1-enyl)-cyclopentyl]-hept-5-enoic acid	KI	861 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-[2-(pyridin-2-yl)ethyl]-1,3-oxazole-4-carboxamide	EC50	1000 nM
ILOPROST	KI	1040 nM
CAS_94079-80-8	KI	1340 nM
CAS_33458-93-4	KI	1420 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-methyl-N-(2-phenylethyl)-1,3-oxazole-4-carboxamide	EC50	2130 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-methyl-1,3-oxazole-4-carboxamide	EC50	3310 nM
N-[2-(dimethylamino)ethyl]-5-{[4-(3-acetamidophenyl)phenyl]methyl}-1,3-oxazole-4-carboxamide	EC50	3310 nM
5-{[4-(3-acetamidophenyl)phenyl]methyl}-N-(propan-2-yl)-1,3-oxazole-4-carboxamide	EC50	3580 nM
U46619	KI	3970 nM
17-PHENYL TRINOR PROSTAGLANDIN E2	KI	4370 nM
CAS_162981	KI	7350 nM
13,14-DIHYDRO-15-KETO PROSTAGLANDIN E2	KI	8410 nM

ChEMBL bioactivities

496 potent at pChembl≥5 of 516 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.40	EC50	0.4	nM	ILOPROST
8.74	EC50	1.8	nM	ALPROSTADIL
8.72	EC50	1.9	nM	TREPROSTINIL
8.70	EC50	2	nM	CHEMBL6019262
8.62	EC50	2.4	nM	ILOPROST
8.57	EC50	2.7	nM	CHEMBL3942683
8.57	EC50	2.7	nM	CHEMBL3890685
8.57	EC50	2.7	nM	CHEMBL3926078
8.57	EC50	2.7	nM	CHEMBL3985726
8.57	EC50	2.7	nM	CHEMBL3984010
8.57	EC50	2.7	nM	CHEMBL3981509
8.57	EC50	2.7	nM	CHEMBL3975122
8.57	EC50	2.7	nM	CHEMBL3981383
8.57	EC50	2.7	nM	CHEMBL3926491
8.57	EC50	2.7	nM	CHEMBL3933704
8.57	EC50	2.7	nM	RALINEPAG
8.57	EC50	2.7	nM	CHEMBL3893346
8.57	EC50	2.7	nM	CHEMBL3943011
8.57	EC50	2.7	nM	CHEMBL3952569
8.57	EC50	2.7	nM	CHEMBL3964788
8.57	EC50	2.7	nM	CHEMBL3907754
8.57	EC50	2.7	nM	CHEMBL3966331
8.57	EC50	2.7	nM	CHEMBL3968835
8.57	EC50	2.7	nM	CHEMBL3928729
8.57	EC50	2.7	nM	CHEMBL3890828
8.57	EC50	2.7	nM	CHEMBL3917222
8.57	EC50	2.7	nM	CHEMBL3914443
8.57	EC50	2.7	nM	CHEMBL3977761
8.57	EC50	2.7	nM	CHEMBL3975263
8.57	EC50	2.7	nM	CHEMBL3902808
8.57	EC50	2.7	nM	CHEMBL3900038
8.57	EC50	2.7	nM	CHEMBL3952237
8.57	EC50	2.7	nM	CHEMBL3943161
8.57	EC50	2.7	nM	CHEMBL3945849
8.57	EC50	2.7	nM	CHEMBL3899229
8.57	EC50	2.7	nM	CHEMBL3984207
8.57	EC50	2.7	nM	CHEMBL3923745
8.57	EC50	2.7	nM	CHEMBL3966307
8.57	EC50	2.7	nM	CHEMBL3933131
8.57	EC50	2.7	nM	CHEMBL3912086
8.57	EC50	2.7	nM	CHEMBL3895137
8.57	EC50	2.7	nM	CHEMBL3922000
8.57	EC50	2.7	nM	CHEMBL3919269
8.57	EC50	2.7	nM	CHEMBL3930990
8.57	EC50	2.7	nM	CHEMBL3935924
8.57	EC50	2.7	nM	CHEMBL3961761
8.57	EC50	2.7	nM	CHEMBL3959044
8.57	EC50	2.7	nM	CHEMBL3979096
8.57	EC50	2.7	nM	CHEMBL3981484
8.57	EC50	2.7	nM	CHEMBL3969137

PubChem BioAssay actives

363 with measured affinity, of 868 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
Iloprost	1872473: Agonist activity at human IP expressed in HEK293 cells assessed as increase in cAMP level incubated for 20 mins measured after 60 mins addition of cAMP detect reagent by HTRF analysis	ec50	0.0004	uM
Alprostadil	161202: Effective concentration which increases intracellular c-AMP production in human Prostanoid IP receptor	ec50	0.0018	uM
Treprostinil	1872473: Agonist activity at human IP expressed in HEK293 cells assessed as increase in cAMP level incubated for 20 mins measured after 60 mins addition of cAMP detect reagent by HTRF analysis	ec50	0.0019	uM
2-[[4-[[(4-chlorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437841: Displacement of [3H]-iloprost from recombinant human IP receptor expressed in CHO-K1 cell membranes incubated for 1 hr by top count scintillation counting method	ki	0.0030	uM
2-[[4-[[(4-methoxyphenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0033	uM
6-[(1R,2S,3R)-3-hydroxy-2-[(E,3S,5S)-3-hydroxy-5-methylnon-1-enyl]-5-oxocyclopentyl]sulfanylhexanoic acid	161209: Evaluated for its competitive binding affinity towards human Prostanoid IP receptor in CHO cells	ki	0.0033	uM
2-[[4-[[(4-chloro-3-fluorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0034	uM
2-[[4-[[(4-methylphenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0039	uM
2-[[6-[[5-(4-methoxyphenyl)-6-oxo-4-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0040	uM
2-[[4-[[(3-fluorophenyl)-(4-methoxyphenyl)carbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0052	uM
2-[[(6R)-6-[[4-(2,3-difluorophenyl)-5-(4-fluorophenyl)-6-oxopyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0060	uM
Selexipag	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0060	uM
sodium 2-[3-[[(1R,2S,6S)-1-(4,5-diphenyl-1,3-oxazol-2-yl)-7-oxabicyclo[4.1.0]heptan-2-yl]methyl]phenoxy]acetate	238503: Inhibition of [3H]-Iloprost binding to human Prostanoid IP receptor	ki	0.0061	uM
2-[[4-[[(4-fluorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0066	uM
2-[[4-[[(3-fluorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437841: Displacement of [3H]-iloprost from recombinant human IP receptor expressed in CHO-K1 cell membranes incubated for 1 hr by top count scintillation counting method	ki	0.0070	uM
2-[[4-[[(3-fluorophenyl)-(4-fluorophenyl)carbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0078	uM
2-[[6-[[3-(4-methoxyphenyl)-6-oxo-4-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0085	uM
2-[[(6R)-6-(diphenylcarbamoyloxymethyl)-6-hydroxy-7,8-dihydro-5H-naphthalen-1-yl]oxy]acetic acid	239198: Displacement of [3H]iloprost from human Prostanoid IP receptor	ki	0.0089	uM
2-[[6-[[4-(3-methoxyphenyl)-3-(4-methylphenyl)-6-oxopyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0095	uM
2-[[6-[[3-(3-fluoro-4-methoxyphenyl)-6-oxo-4-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0100	uM
2-[[6-[[4-(2-fluoro-3-methoxyphenyl)-6-oxo-5-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0100	uM
2-[[4-[[(3,4-difluorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0100	uM
2-[(2R,4aR,5R,6R,7aS)-6-hydroxy-5-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran-2-yl]-1,3-thiazole-4-carboxylic acid	1300194: Agonist activity at human IP receptor expressed in CHO cells assessed as increase in intracellular cAMP level after 30 mins by HTRF method	ec50	0.0110	uM
sodium 2-[[(5R)-5-[(2R)-2-(4,5-diphenyl-1,3-oxazol-2-yl)pyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetate	238689: Ability to inhibit binding of [3H]iloprost to cloned human prostaglandin I2 receptor	ki	0.0120	uM
2-[[4-[[(3-methoxyphenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0120	uM
2-[[4-[2-(N-benzoyl-4-chloroanilino)ethyl]-2,3-dihydro-1,4-benzoxazin-8-yl]oxy]acetic acid	1293855: Agonist activity at human IP receptor in platelet rich plasma assessed as inhibition of ADP-induced platelet aggregation preincubated for 1 min followed by addition of ADP by aggregometry	ic50	0.0130	uM
(2S)-2-[[5-[[4-(3-acetamidophenyl)phenyl]methyl]-1,3-oxazole-4-carbonyl]amino]-3-phenylpropanoic acid	298802: Antagonist activity at human IP receptor in HEL 92.1.7 cells assessed as inhibition of iloprost-induced cAMP production	ic50	0.0160	uM
2-[[4-[[(4-chlorophenyl)-(3-fluorophenyl)carbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0185	uM
2-[[4-[[(3-chlorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0190	uM
2-[[6-[[3-(2-fluoro-4-methoxyphenyl)-6-oxo-4-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0200	uM
2-[[6-[[5-(4-fluorophenyl)-6-oxo-4-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0200	uM
2-[[4-(diphenylcarbamoyloxymethyl)cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0210	uM
2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0220	uM
2-[[4-[[(4-chloro-3-fluorophenyl)-(3-fluorophenyl)carbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0230	uM
2-[[6-[[3-(4-methylphenyl)-6-oxo-4-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0240	uM
7-[(1R,2R,3R)-3-hydroxy-2-[(E,4S)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]heptanoic acid	1151369: Agonist activity at prostanoid IP receptor (unknown origin) by functional assay	ic50	0.0250	uM
7-[(1R,3R)-3-hydroxy-2-[(E,4S)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]heptanoic acid	161202: Effective concentration which increases intracellular c-AMP production in human Prostanoid IP receptor	ec50	0.0250	uM
2-[[4-[[(4-chlorophenyl)-(4-hydroxyphenyl)carbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0250	uM
N-[4-[(4-methoxyphenyl)methyl]phenyl]-4,5-dihydro-1H-imidazol-2-amine	160525: Binding affinity towards prostacyclin receptor on rat NG-108-15 neuroblastoma cells, using [3H]iloprost as a radioligand	ki	0.0251	uM
4-[(2R,4aR,5R,6R,7aS)-6-hydroxy-5-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran-2-yl]butanoic acid	1331419: Agonist activity at human IP receptor expressed in CHO cells assessed as increase in intracellular cAMP level by HTRF method	ec50	0.0260	uM
N-[4-(4-propan-2-yloxyphenyl)sulfanylphenyl]-4,5-dihydro-1H-imidazol-2-amine	160525: Binding affinity towards prostacyclin receptor on rat NG-108-15 neuroblastoma cells, using [3H]iloprost as a radioligand	ki	0.0316	uM
2-[[6-[[4-(2,3-difluorophenyl)-5-(4-fluorophenyl)-6-oxopyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0330	uM
2-[2-methyl-1-[4-[[(2S)-4-methyl-2,3-dihydro-1,4-benzoxazin-2-yl]methoxy]benzoyl]indol-4-yl]acetic acid	611099: Displacement of [3H]-Iloprost from human IP receptor expressed in CHO cells after 30 mins by liquid scintillation counting	ki	0.0370	uM
2-[[6-[[4-(2-fluoro-3-methoxyphenyl)-6-oxo-3-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0370	uM
methyl 7-[(1R,3R)-3-hydroxy-2-[(E,4S)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]heptanoate	161202: Effective concentration which increases intracellular c-AMP production in human Prostanoid IP receptor	ec50	0.0370	uM
methyl 7-[(1R,2R,3R)-3-hydroxy-2-[(E,4R)-4-hydroxy-4-(1-propylcyclobutyl)but-1-enyl]-5-oxocyclopentyl]heptanoate	1151369: Agonist activity at prostanoid IP receptor (unknown origin) by functional assay	ic50	0.0370	uM
2-[[6-[[4-(2,3-difluorophenyl)-6-oxo-5-phenylpyridazin-1-yl]methyl]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]acetic acid	1191856: Agonist activity at human recombinant IP receptor expressed in CHO-K1 cells incubated for 1 hr by HTRF cAMP assay	ec50	0.0380	uM
2-[[4-[[(3-chloro-4-fluorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid	1437825: Agonist activity at recombinant human IP receptor expressed in CHO-K1 cells assessed as increase in intracellular cAMP level after 1 hr incubation by HTRF method	ec50	0.0380	uM
sodium 2-[3-[[(1S,2R)-2-(4,5-diphenyl-1,3-oxazol-2-yl)cyclopentyl]methyl]phenoxy]acetate	271029: Agonist activity at human PGI2 receptor assessed as inhibition of ADP-induced platelet aggregation	ic50	0.0390	uM
N-[4-(4-ethoxyphenyl)sulfanylphenyl]-4,5-dihydro-1H-imidazol-2-amine	160525: Binding affinity towards prostacyclin receptor on rat NG-108-15 neuroblastoma cells, using [3H]iloprost as a radioligand	ki	0.0398	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
mevalonolactone	affects binding	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
cicaprost	affects binding, increases reaction, increases abundance, increases activity, affects localization	1
pentanal	increases expression	1
beraprost	affects binding, increases activity, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Cyclic AMP	increases abundance, increases activity, increases reaction	1
Aldehydes	increases expression	1
Asbestos	increases expression	1
Aspirin	affects response to substance	1
Calcium	increases abundance, increases activity	1
Cannabinoids	affects methylation, increases abundance	1
Dexamethasone	affects cotreatment, increases expression, decreases expression	1
Indomethacin	decreases expression, affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Silicon Dioxide	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression, decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1

ChEMBL screening assays

156 unique, capped per target: 124 binding, 31 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009660	Binding	Inhibition of IP receptor	Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain. — Bioorg Med Chem Lett
CHEMBL2412172	Functional	Antagonist activity at human IP receptor overexpressed in rat C6 cells assessed as inhibition of iloprost-induced cAMP accumulation incubated for 10 mins prior to iloprost addition measured after 40 mins by TR-FRET assay	Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists. — ACS Med Chem Lett
CHEMBL3871199	ADMET	Agonist activity at human IP receptor expressed in CHO cells assessed as increase in intracellular cAMP level by HTRF method	Discovery of Novel Seven-Membered Prostacyclin Analogues as Potent and Selective Prostaglandin FP and EP3 Dual Agonists. — ACS Med Chem Lett

Cellosaurus cell lines

7 cell lines: 4 spontaneously immortalized cell line, 2 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TN	ACTOne PTGIR	Transformed cell line	Female
CVCL_H451	CHO-K1/IP1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV69	cAMP Hunter CHO-K1 PTGIR Gs	Spontaneously immortalized cell line	Female
CVCL_KY89	PathHunter CHO-K1 PTGIR beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ64	PathHunter HEK 293 PTGIR beta-arrestin	Transformed cell line	Female
CVCL_LB23	PathHunter U2OS PTGIR Total GPCR Internalization	Cancer cell line	Female
CVCL_ZK82	GeneBLAzer PTGIR-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01745666	Not specified	UNKNOWN	Comparison Between Epinephrine and Exercise Test in QT Long Syndrome Patients