S1PR2

Summary

S1PR2 (sphingosine-1-phosphate receptor 2, HGNC:3169) is a protein-coding gene on chromosome 19p13.2, encoding Sphingosine 1-phosphate receptor 2 (O95136). Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P).

This gene encodes a member of the G protein-coupled receptors, as well as the EDG family of proteins. The encoded protein is a receptor for sphingosine 1-phosphate, which participates in cell proliferation, survival, and transcriptional activation. Defects in this gene have been associated with congenital profound deafness.

Source: NCBI Gene 9294 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Strong, ClinGen) — +2 more curated relationships
• GWAS associations: 23
• Clinical variants (ClinVar): 152 total — 2 pathogenic
• GTEx eGene: eQTL in 18 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 3
• Drug target: yes — 3 via a complex or family; 1 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 2 — Fingolimod Hydrochloride, Fingolimod Lauryl Sulfate (Sphingosine 1-phosphate receptor)
• Constraint (gnomAD): pLI 0.06 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• MANE Select transcript: NM_004230

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3169
Approved symbol	S1PR2
Name	sphingosine-1-phosphate receptor 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	Gpcr13, H218, AGR16
Ensembl gene	ENSG00000267534
Ensembl biotype	protein_coding
OMIM	605111
Entrez	9294

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000646641

ENST00000646641

RefSeq mRNA: 1 — MANE Select: NM_004230 NM_004230

CCDS: CCDS12229

Canonical transcript exons

ENST00000646641 — 2 exons

Exon	Start	End
ENSE00001237868	10221433	10224947
ENSE00003827265	10231204	10231331

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 87.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7441 / max 106.6699, expressed in 1650 samples.

Highest expression (Bgee): ventricle myocardium, epithelial cell of pancreas, heart right ventricle, cardiac muscle of right atrium, vena cava.

Genetic regulation across tissues (GTEx eQTL / sQTL)

S1PR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	9.8e-13	+0.28	19:10236408:T:C
Cells Cultured fibroblasts	eqtl	1.6e-11	+0.18	19:10233923:C:G
Liver	eqtl	2.8e-10	+0.61	19:10236356:C:T
Artery Aorta	eqtl	3.2e-09	+0.33	19:10229142:G:C
Brain Spinal cord cervical c-1	eqtl	9.2e-09	-0.56	19:10231337:G:T
Brain Cortex	eqtl	7.7e-06	-0.44	19:10259457:G:A
Nerve Tibial	eqtl	1.1e-04	+0.15	19:10233923:C:G
Colon Sigmoid	eqtl	6.7e-04	-0.26	19:10268001:A:T
Skin Sun Exposed Lower leg	eqtl	2.5e-03	+0.10	19:10233923:C:G
Stomach	eqtl	8.2e-03	+0.17	19:10236408:T:C
Breast Mammary Tissue	eqtl	1.6e-02	-0.21	19:10216725:G:A
Heart Atrial Appendage	eqtl	1.8e-02	+0.24	19:10295189:C:T
Testis	eqtl	2.8e-02	+0.39	19:9233439:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.0e-02	+0.10	19:10242326:G:A
Adipose Visceral Omentum	eqtl	3.2e-02	-0.18	19:10268001:A:T
Adipose Subcutaneous	eqtl	4.4e-02	-0.13	19:10258410:C:T
Brain Cerebellar Hemisphere	eqtl	4.5e-02	+0.24	19:10251254:CCTAAT:C
Whole Blood	eqtl	5.0e-02	-0.19	19:9992089:G:C
Artery Aorta	sqtl	5.0e-02	+1.26	19:9823780:A:G
Artery Tibial	sqtl	5.0e-02	+1.40	19:9898103:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
179095	9.7441	1650

Top tissues by expression

showing 100 of 242 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	87.58	gold quality
epithelial cell of pancreas	CL:0000083	87.13	silver quality
heart right ventricle	UBERON:0002080	86.91	silver quality
cardiac muscle of right atrium	UBERON:0003379	85.26	gold quality
vena cava	UBERON:0004087	85.12	silver quality
stromal cell of endometrium	CL:0002255	84.66	gold quality
parotid gland	UBERON:0001831	83.91	silver quality
placenta	UBERON:0001987	83.12	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.72	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	81.86	gold quality
upper lobe of left lung	UBERON:0008952	81.36	gold quality
upper lobe of lung	UBERON:0008948	80.97	gold quality
pancreatic ductal cell	CL:0002079	80.96	silver quality
sperm	CL:0000019	80.91	silver quality
left uterine tube	UBERON:0001303	80.55	gold quality
mucosa of stomach	UBERON:0001199	80.42	gold quality
endocervix	UBERON:0000458	79.98	gold quality
buccal mucosa cell	CL:0002336	79.80	gold quality
visceral pleura	UBERON:0002401	79.72	gold quality
trachea	UBERON:0003126	79.15	gold quality
pericardium	UBERON:0002407	79.11	silver quality
deltoid	UBERON:0001476	78.49	silver quality
left testis	UBERON:0004533	78.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.36	silver quality
lung	UBERON:0002048	78.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	78.31	gold quality
right testis	UBERON:0004534	78.30	gold quality
right lung	UBERON:0002167	78.17	gold quality
lymph node	UBERON:0000029	77.81	gold quality
tongue	UBERON:0001723	77.43	silver quality
parietal pleura	UBERON:0002400	77.42	gold quality
testis	UBERON:0000473	77.40	gold quality
tonsil	UBERON:0002372	77.37	gold quality
saphenous vein	UBERON:0007318	77.36	silver quality
kidney epithelium	UBERON:0004819	77.31	gold quality
pharyngeal mucosa	UBERON:0000355	77.15	silver quality
superior surface of tongue	UBERON:0007371	77.10	gold quality
mammalian vulva	UBERON:0000997	77.00	silver quality
caecum	UBERON:0001153	76.93	gold quality
cartilage tissue	UBERON:0002418	76.93	gold quality
lateral globus pallidus	UBERON:0002476	76.83	gold quality
biceps brachii	UBERON:0001507	76.72	gold quality
epithelium of mammary gland	UBERON:0003244	76.68	silver quality
endothelial cell	CL:0000115	76.63	silver quality
mammary duct	UBERON:0001765	76.57	silver quality
vastus lateralis	UBERON:0001379	76.48	gold quality
cardia of stomach	UBERON:0001162	76.22	silver quality
pylorus	UBERON:0001166	75.98	silver quality
cardiac atrium	UBERON:0002081	75.93	gold quality
body of uterus	UBERON:0009853	75.93	gold quality
muscle tissue	UBERON:0002385	75.90	gold quality
ectocervix	UBERON:0012249	75.87	gold quality
myometrium	UBERON:0001296	75.81	gold quality
uterine cervix	UBERON:0000002	75.80	gold quality
peritoneum	UBERON:0002358	75.78	gold quality
omental fat pad	UBERON:0010414	75.76	gold quality
mammary gland	UBERON:0001911	75.74	gold quality
gall bladder	UBERON:0002110	75.73	gold quality
esophagus squamous epithelium	UBERON:0006920	75.68	silver quality
thoracic mammary gland	UBERON:0005200	75.67	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.57	gold quality
gingival epithelium	UBERON:0001949	75.45	silver quality
vermiform appendix	UBERON:0001154	75.41	gold quality
right atrium auricular region	UBERON:0006631	75.36	gold quality
skeletal muscle tissue	UBERON:0001134	75.28	silver quality
nipple	UBERON:0002030	75.27	gold quality
oviduct epithelium	UBERON:0004804	75.15	gold quality
layer of synovial tissue	UBERON:0007616	75.03	silver quality
substantia nigra pars reticulata	UBERON:0001966	74.99	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.92	silver quality
lower esophagus muscularis layer	UBERON:0035833	74.89	gold quality
lower esophagus	UBERON:0013473	74.82	gold quality
pons	UBERON:0000988	74.81	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	74.73	gold quality
decidua	UBERON:0002450	74.62	gold quality
amniotic fluid	UBERON:0000173	74.55	gold quality
female reproductive system	UBERON:0000474	74.55	gold quality
urinary bladder	UBERON:0001255	74.48	gold quality
superficial temporal artery	UBERON:0001614	74.42	silver quality
subcutaneous adipose tissue	UBERON:0002190	74.40	gold quality
right ovary	UBERON:0002118	74.38	gold quality
uterus	UBERON:0000995	74.23	gold quality
ventral tegmental area	UBERON:0002691	74.22	gold quality
apex of heart	UBERON:0002098	74.19	gold quality
adipose tissue	UBERON:0001013	74.17	gold quality
lower lobe of lung	UBERON:0008949	74.11	gold quality
gingiva	UBERON:0001828	74.06	silver quality
vagina	UBERON:0000996	73.90	gold quality
tibia	UBERON:0000979	73.70	gold quality
fallopian tube	UBERON:0003889	73.57	gold quality
heart	UBERON:0000948	73.54	gold quality
tibial nerve	UBERON:0001323	73.43	gold quality
cerebellar vermis	UBERON:0004720	73.42	gold quality
colonic epithelium	UBERON:0000397	73.03	silver quality
prostate gland	UBERON:0002367	73.01	gold quality
skin of leg	UBERON:0001511	73.00	gold quality
dorsal root ganglion	UBERON:0000044	72.94	silver quality
trigeminal ganglion	UBERON:0001675	72.90	silver quality
cardiac ventricle	UBERON:0002082	72.82	gold quality
fundus of stomach	UBERON:0001160	72.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	20.48
E-MTAB-7051	no	2855.68
E-MTAB-5061	no	3.71

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	17.3	not detected
Olfactory bulb	tissue	17.0
Cerebellum	tissue	14.3	not detected
Cerebral cortex	tissue	13.4	not detected
Insular cortex	tissue	13.4
Amygdala	tissue	12.8
Retrosplenial and cingulate cortex	tissue	12.4
Retrosplenial cortex	tissue	12.2
Temporal cortex	tissue	12.1
Hippocampal formation	tissue	11.7
Entorhinal cortex	tissue	11.7
Basal ganglia	tissue	11.6	not detected
Prefrontal cortex	tissue	11.1
Occipital cortex	tissue	11.0
Corpus callosum	tissue	10.8
Septum	tissue	10.6
Motor cortex	tissue	10.5
Ventral forebrain	tissue	10.5
Spinal cord	tissue	10.3
Lymph node	tissue	10.2	not detected
Tonsil	tissue	10.2	not detected
Somatosensory cortex	tissue	10.0
Periaqueductal gray	tissue	9.1
Putamen	tissue	9.0
Hypothalamus	tissue	8.6
Substantia nigra	tissue	8.6
Midbrain	tissue	7.7
Medulla oblongata	tissue	7.6
Cervix	tissue	7.4	not detected
Thalamus	tissue	7.0
Superior colliculi	tissue	6.9
Pons	tissue	6.7
Vagina	tissue	6.5	not detected
Appendix	tissue	6.1	not detected
Gallbladder	tissue	5.8	not detected
Lung	tissue	5.5	not detected
Urinary bladder	tissue	5.1	not detected
Endometrium 1	tissue	5.0	not detected
Choroid plexus	tissue	5.0
Testis	tissue	4.6	not detected
Adipose tissue	tissue	4.3	not detected
Locus coeruleus	tissue	4.3
Smooth muscle	tissue	3.9	not detected
Salivary gland	tissue	3.8	not detected
Hippocampus	tissue	3.7	not detected
Breast	tissue	3.5	not detected
Nucleus accumbens	tissue	3.5
Prostate	tissue	3.3	not detected
Postcentral gyrus	tissue	3.1
Skin 1	tissue	2.9	not detected
Pituitary gland	tissue	2.8
Liver	tissue	2.8	not detected
Ovary	tissue	2.6	not detected
Esophagus	tissue	2.6	not detected
Epididymis	tissue	2.6	not detected
Fallopian tube	tissue	2.5	not detected
Parathyroid gland	tissue	2.4	not detected
Rectum	tissue	2.3	not detected
Seminal vesicle	tissue	2.2
Colon	tissue	2.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Subiculum (10.8), White matter (10.8), Ventral hippocampus (10.7), Dorsal spinal cord (10.3), Dorsal hippocampus (9.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting S1PR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 123 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4728-5P	99.85	69.39	4718

Functional genomics

gnomAD constraint: pLI 0.0559, LOEUF 0.834, missense Z 2.24 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000646641 — one region, missense o/e 0.74.

Literature-anchored findings (GeneRIF, showing 40)

• suppress rac protein, a Rho family G protein and cell motility (PMID:11915348)
• Amyloid beta-protein stimulated in monocytes the gene expression for sphingosine-1-phosphate receptor 5, which is amyloid beta-protein-induced migration. (PMID:15208267)
• S1P2R receptor actively regulates the PTEN phosphatase by a Rho GTPase-dependent pathway to inhibit cell migration. (PMID:15764699)
• S1P2R activation in endothelial cells increases vascular permeability. The balance of S1P1 and S1P2 receptors in the endothelium may determine the regulation of vascular permeability by S1P. (PMID:17431187)
• antagonism of the S1P2R may be a novel therapeutic approach for the prevention and/or treatment of pathologic ocular neovascularization (PMID:17710232)
• These results suggest that S1P(2) receptors/G(12/13)-proteins/Rho signaling pathways mediate S1P-induced inhibition of glioma cell migration. (PMID:18088600)
• Results suggest that S1PR2 is involved in COX2 dependent effects of high-density lipoprotein on vascular smooth muscle. (PMID:18612546)
• Plays essential roles in the pathogenesis of rheumatoid arthritis by modulating fibroblast-like synoviocytes migration, cytokine/chemokine production, and cell survival. (PMID:18658144)
• impairment of function in senescent ECs in culture is mediated by an increase in S1P signaling through S1P(2)-mediated activation of the lipid phosphatase PTEN (PMID:18765664)
• These data suggest that CTGF protein induced by S1P2 might act as a growth inhibitor in Wilms’ tumor. (PMID:18922980)
• the S1P(2) receptor is involved in S1P-induced platelet aggregation and Rho kinase activation. (PMID:19139947)
• S1P(2) signaling may play a critical role in suppressing diffuse large B-cell lymphoma (PMID:19903857)
• S1PR2 receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release (PMID:20194630)
• SphK/S1P/S1PRs signaling axis plays an important role in liver fibrosis and is involved in the directed migration of hepatic myofibroblasts into the damaged areas. (PMID:21145832)
• S1P2, and not S1P1 or S1P3, receptor activation increases conventional outflow resistance in whole-eye perfusions. (PMID:21289286)
• Inflammatory mediators lipopolysaccharide and TNF-alpha induce S1PR2 expression in endothelium, suggesting that S1PR2 up-regulation may be involved in LPS and TNF-alpha elicited endothelial barrier dysfunction. (PMID:22244964)
• abdominal aortic aneurysms have down-regulation of the S1P2 protein with simultaneous up-regulation of the S1P3 protein, but not S1P1 (PMID:22547907)
• S1P receptors S1P1,2,3 are expressed in human anaplastic thyroid cancer C643 and THJ-16T cells at both mRNA and protein levels (PMID:22889737)
• identify the S1PR2 as the specific and necessary receptor to induce phosphorylation of ERM proteins and subsequent filopodia formation (PMID:23106337)
• Sphingosine 1-phosphate (S1P) receptors 1 and 2 coordinately induce mesenchymal cell migration through S1P activation of complementary kinase pathways (PMID:23300082)
• S1PR agonists are pro-fibrotic via S1P2R and S1P3R stimulation using Smad-independent pathways. (PMID:23589284)
• Data indicate that EGF-induced cellular invasion required sphingosine-1-phosphate (S1P)-mediated activation of sphingosine-1-phosphate 2 receptor (S1PR2) and ezrin phosphorylation. (PMID:23629860)
• Activation of the S1P2 receptor counteracts the detrimental phosphorylation of p38 MAPK by IL-1beta. (PMID:23666803)
• S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium. (PMID:23723450)
• TNFalpha treatment activates autocrine S1P/S1P2 signaling, which subsequently activates NFkappaB and leads to the proinflammatory responses in endothelial cell (PMID:23770055)
• The S1P2R specifically activates RhoC via G12/13 proteins and LARG. (PMID:23993968)
• we provide evidences that S1PR1/3, but not S1PR2, negatively regulate the expression of collagen in hMSCs using cellular and molecular approaches (PMID:24038457)
• extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. (PMID:24064301)
• Sphingosylphosphorylcholine stimulates alpha-SMA protein expression and human lung fibroblast mediated collagen gel contraction via S1P2 receptor. (PMID:24614064)
• Conjugated bile acids promote cholangiocarcinoma growth through S1PR2. (PMID:24700501)
• S1PR2 expression was increased in disease-susceptible regions of the CNS of female patients with multiple sclerosis compared with their male counterparts. (PMID:24812668)
• Data indicate that sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) induced transloaction of integrin beta4, S1P receptors S1PR2 and S1PR3 to endothelial cell membrane caveolin-enriched microdomains (CEMs). (PMID:24851274)
• Data show that sphingosine kinase SphK1 and sphingosine-1-phosphate (S1P) receptors S1P1, S1P2, S1P3, and S1P5 were expressed from primary, up to recurrent and secondary glioblastomas, with sphingosine kinase SphK2 levels were highest in primary tumors. (PMID:24903384)
• Activation of S1PR2-calcium influx-RhoA/ROCK dominates the high-dose S1P-induced endothelial monolayer hyperpermeability response. (PMID:25557733)
• both S1PR1 and S1PR2 play a pivotal role in hyperglycemia-induced EC dysfunction and endothelial injury by reducing and enhancing the production of oxidative stress. (PMID:25673082)
• AB1 displayed potency at least equivalent to JTE-013 in affecting signaling molecules downstream of S1P2. (PMID:26105954)
• be detected in the human cerebrovascular endothelium (PMID:26243335)
• Sphingosine 1-phosphate-induced IL-8 gene expression is mainly regulated via S1PR(1), and its secretion is regulated through S1PR(2) receptor subtype. (PMID:26321412)
• S1PR2 plays a critical role in TCA-induced COX-2 expression and CCA growth and may represent a novel therapeutic target for CCA. (PMID:26518876)
• S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells. (PMID:26631556)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	s1pr2	ENSDARG00000036548
mus_musculus	S1pr2	ENSMUSG00000043895
rattus_norvegicus	S1pr2	ENSRNOG00000020653

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99569) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 58 distinct phenotype terms.

Mouse phenotype (MP)	Records
deafness	3
seizures	3
decreased otolith number	3
cochlear outer hair cell degeneration	3
increased or absent threshold for auditory brainstem response	3
organ of Corti degeneration	2
premature death	2
thin stria vascularis	2
abnormal strial marginal cell morphology	2
abnormal stria vascularis vasculature morphology	2
increased T cell number	2
head tilt	2
increased germinal center B cell number	2
abnormal organ of Corti morphology	1
abnormal stria vascularis morphology	1
impaired swimming	1
decreased litter size	1
increased B cell derived lymphoma incidence	1
abnormal CNS synaptic transmission	1
abnormal nervous system electrophysiology	1
abnormal spleen germinal center morphology	1
abnormal spleen marginal zone morphology	1
cochlear ganglion degeneration	1
abnormal excitatory postsynaptic currents	1
enlarged otoliths	1

+33 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q95KH4	98.6%	Diamond
Xenopus laevis	Q9PU16	98.4%	Diamond
Ovis aries	P46628	97.8%	Diamond
Bos taurus	Q28031	97.8%	Diamond
Felis catus	O02777	96.8%	Diamond
Sus scrofa	Q684M3	86.7%	Diamond
Takifugu rubripes	Q9PUQ8	69.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LIMASI	ncRNA	105372272
ICAM4-AS1	ncRNA	123706506
DNMT1	protein-coding	1786
ICAM1	protein-coding	3383
MRPL4	protein-coding	51073
MIR4322	ncRNA	100422925
P2RY11	protein-coding	5032
PPAN-P2RY11	protein-coding	692312
EIF3G	protein-coding	8666
ICAM4	protein-coding	3386
ICAM5	protein-coding	7087
SNORD105B	snoRNA	100113382
PPAN	protein-coding	56342
ZGLP1	protein-coding	100125288
FDX2-ZGLP1	ncRNA	125242785

Protein

Protein identifiers

Sphingosine 1-phosphate receptor 2 — O95136 (reviewed: O95136)

Alternative names: Endothelial differentiation G protein-coupled receptor 5, Sphingosine 1-phosphate receptor Edg-5

All UniProt accessions (1): O95136

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effects on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis. Receptor for the chemokine-like protein FAM19A5. Mediates the inhibitory effect of FAM19A5 on vascular smooth muscle cell proliferation and migration. In lymphoid follicles, couples the binding of S1P to the activation of GNA13 and downstream inhibition of AKT activation leading to suppression of germinal center (GC) B cell growth and migration outside the GC niche.

Subcellular location. Cell membrane.

Disease relevance. Deafness, autosomal recessive, 68 (DFNB68) [MIM:610419] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_004221* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR004061	S1P_rcpt	Family
IPR004063	EDG5_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (46 total): helix 12, topological domain 8, mutagenesis site 8, transmembrane region 7, sequence variant 2, sequence conflict 2, turn 2, strand 2, chain 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7T6B	Structure of S1PR2-heterotrimeric G13 signaling complex	ELECTRON MICROSCOPY	3.19
9W0M	Cryo-EM structure of S1P2 in complex with heterotrimeric G protein	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95136-F1	82.73	0.56

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 7T6B

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Lysolipids receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Disease related genes, Potential drug targets, Human disease related genes, Ear disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; nuclear speckles

Antibody reliability (HPA): IH approved · IF uncertain

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 (1)

Type	Positions
S-palmitoyl cysteine	305

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	19

Mutagenesis-validated functional residues (8)

Position	Phenotype
147	no effect on protein expression at the cell surface. decreases s1pr2-mediated inhibition of akt activation and b cell migration. loss of …
156	loss of protein expression.
194	loss of protein expression.
245	markedly decreases protein expression.
248	loss of protein expression.
256	loss of protein expression.
272	decreases protein expression. no effect on s1p-mediated inhibition of akt signaling, gc b cell growth and migration.
329	no effect on protein expression or s1pr2-mediated inhibition of akt activation and b cell migration.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-418594	G alpha (i) signalling events	curated
R-HSA-419408	Lysosphingolipid and LPA receptors	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 215 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, CREL_01, GOBP_EPITHELIUM_DEVELOPMENT, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_SYNAPSE_ASSEMBLY, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_SPHINGOLIPID_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, AAAYRNCTG_UNKNOWN, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION

GO Biological Process (9): sphingosine-1-phosphate receptor signaling pathway (GO:0003376), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of cell population proliferation (GO:0008284), actin cytoskeleton organization (GO:0030036), filopodium assembly (GO:0046847), regulation of postsynapse assembly (GO:0150052), positive regulation of establishment of endothelial barrier (GO:1903142), signal transduction (GO:0007165)

GO Molecular Function (7): G protein-coupled receptor binding (GO:0001664), G protein-coupled receptor activity (GO:0004930), integrin binding (GO:0005178), lipid binding (GO:0008289), G protein-coupled peptide receptor activity (GO:0008528), sphingosine-1-phosphate receptor activity (GO:0038036), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), plasma membrane (GO:0005886), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

36 GO namespaces:

Category	Terms
cellular anatomical structure	3
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor activity	2
signaling receptor binding	2
binding	2
synapse	2
sphingolipid mediated signaling pathway	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cytoskeleton organization	1
actin filament-based process	1
plasma membrane bounded cell projection assembly	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
establishment of endothelial barrier	1
positive regulation of endothelial cell development	1
regulation of establishment of endothelial barrier	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
protein-containing complex binding	1
cell adhesion molecule binding	1
peptide receptor activity	1
sphingosine-1-phosphate receptor signaling pathway	1
bioactive lipid receptor activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway	BP	direct assay
actin cytoskeleton organization	BP	mutant phenotype
filopodium assembly	BP	mutant phenotype
positive regulation of establishment of endothelial barrier	BP	mutant phenotype
sphingosine-1-phosphate receptor signaling pathway	BP	mutant phenotype
plasma membrane	CC	direct assay
G protein-coupled peptide receptor activity	MF	physical interaction
G protein-coupled receptor binding	MF	physical interaction
integrin binding	MF	physical interaction
sphingosine-1-phosphate receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,054 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S1PR2	SPHK1	Q9NYA1	924
S1PR2	SPHK2	Q9NRA0	863
S1PR2	SGPL1	O95470	691
S1PR2	SPNS2	Q8IVW8	687
S1PR2	GPBAR1	Q8TDU6	685
S1PR2	MFSD2B	A6NFX1	660
S1PR2	P2RY8	Q86VZ1	636
S1PR2	NR1H4	Q96RI1	603
S1PR2	APOM	O95445	600
S1PR2	NR1I3	Q14994	593
S1PR2	GPR183	P32249	584
S1PR2	BCL6	P41182	576
S1PR2	GNA12	Q03113	569
S1PR2	GNA13	Q14344	567
S1PR2	NR1I2	O75469	547

IntAct

Human interaction partners of S1PR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
PALM3	association	0.530	2
ITGB4	physical association	0.400	2
S1PR1	proximity	0.270	1

BioGRID (63 interactions; top human partners by supporting records): ARL6IP5 (Affinity Capture-MS; 2 records), ARVCF (Affinity Capture-MS; 2 records), ATP5B (Affinity Capture-MS; 2 records), C8G (Affinity Capture-MS; 2 records), CSNK1G3 (Affinity Capture-MS; 2 records), FKBP14 (Affinity Capture-MS; 2 records), GAP43 (Affinity Capture-MS; 2 records), HPCAL1 (Affinity Capture-MS; 2 records), LGALS1 (Affinity Capture-MS; 2 records), NDRG1 (Affinity Capture-MS; 2 records), PALM3 (Affinity Capture-MS; 2 records), PTER (Affinity Capture-MS; 2 records), SRC (Affinity Capture-MS; 2 records), WDFY1 (Affinity Capture-MS; 2 records), ACP2 (Affinity Capture-MS)

SIGNOR signaling

showing 15 of 16 signaling interactions:

A	Effect	B	Mechanism
“sphingosine 1-phosphate”	up-regulates	S1PR2	“chemical activation”
S1PR2	up-regulates	GNA12	binding
S1PR2	up-regulates	GNA13	binding
S1PR2	“up-regulates activity”	GNAI1	binding
S1PR2	“up-regulates activity”	GNAI3	binding
S1PR2	“up-regulates activity”	GNAO1	binding
S1PR2	“up-regulates activity”	GNAZ	binding
S1PR2	“up-regulates activity”	GNAQ	binding
S1PR2	“up-regulates activity”	GNA14	binding
S1PR2	“up-regulates activity”	GNA12	binding
S1PR2	“up-regulates activity”	GNA13	binding
“sphingosine 1-phosphate(1-)”	“up-regulates activity”	S1PR2	“chemical activation”
S1PR2	up-regulates	GNAI1	binding
S1PR2	up-regulates	GNAQ	binding
“sphingosine 1-phosphate”	“up-regulates activity”	S1PR2	“chemical activation”

Protein complexes (CORUM) (8)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

8 complexes by size:

Complex	Subunits	Members
★ KDR-MAPK1-MAPK3-PRKCA-S1PR2 complex	5	PRKCA, S1PR2, KDR, MAPK1, MAPK3
LPAR1-S1PR2 complex	2	LPAR1, S1PR2
LPAR2-S1PR2 complex	2	LPAR2, S1PR2
LPAR3-S1PR2 complex	2	LPAR3, S1PR2
GPR4-S1PR2 complex	2	GPR4, S1PR2
ITGB4-S1PR2 complex	2	ITGB4, S1PR2
★ S1PR1-S1PR2 complex	2	S1PR1, S1PR2
Sphingosine 1-phosphate receptor 2	1	S1PR2

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
TAFA5	receptor	Signaling by TAFA

Disease & clinical

Genetic variants

Variant evidence for S1PR2: 152 ClinVar records (2 pathogenic / likely pathogenic); 23 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	76
Likely benign	47
Benign	9

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
219249	NM_004230.4(S1PR2):c.419A>G (p.Tyr140Cys)	Pathogenic	no assertion criteria provided	2
219259	NM_004230.4(S1PR2):c.323G>C (p.Arg108Pro)	Pathogenic	no assertion criteria provided	2

Per-variant reference — Sugi Variant

Explore S1PR2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 260):

Position(s)	Effect	Δscore	Sites
19:10224948–10224949	acceptor_loss	0.9900	6
19:10231202–10231203	donor_loss	0.9900	5
19:10224952	acceptor_gain	0.9700
19:10224961	acceptor_loss	0.9700
19:10230921	donor_gain	0.9700
19:10230211	donor_gain	0.9600
19:10230885	donor_gain	0.9300
19:10231202	donor_loss	0.9000
19:10224965	acceptor_loss	0.8900
19:10230917	donor_gain	0.8900

AlphaMissense

898 missense substitutions predicted likely pathogenic (of 2,245 scored), across 230 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N51	8	0.997	0.998
D79	8	0.997	0.999
D256	8	0.986	0.994
F242	8	0.981	0.997
N284	8	0.974	0.995
F106	8	0.939	0.994
F71	8	0.938	0.986
F113	8	0.935	0.986
F250	8	0.934	0.984
F274	8	0.919	0.982
N280	8	0.912	0.993
N171	8	0.900	0.992
C179	7	0.992	0.997
C172	7	0.991	0.998
W246	7	0.973	0.997
W156	7	0.971	0.998
W105	7	0.970	0.995
E129	7	0.960	0.995
F86	7	0.959	0.991
E109	7	0.959	0.983

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (validation)	favorable	3.87e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	7.84e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000229

Disease associations

OMIM: gene MIM:605111 | disease phenotypes: MIM:610419

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
nonsyndromic genetic hearing loss	Strong	Unknown
autosomal recessive nonsyndromic hearing loss 68	Strong	Autosomal recessive	2
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Strong	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Monogenic hearing loss	green
Paediatric disorders	green

Mondo (3): autosomal recessive nonsyndromic hearing loss 68 (MONDO:0012485), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (1): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636)

HPO phenotypes

3 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0003593	Infantile onset

GWAS associations

23 associations:

Study	Trait	p-value
GCST004622_81	Reticulocyte count	7e-26
GCST90013406_205	Liver enzyme levels (alkaline phosphatase)	2e-23
GCST004619_12	Reticulocyte fraction of red cells	3e-23
GCST90002386_594	High light scatter reticulocyte percentage of red cells	9e-21
GCST90002385_300	High light scatter reticulocyte count	2e-20
GCST90013405_127	Liver enzyme levels (alanine transaminase)	3e-20
GCST90002406_31	Reticulocyte fraction of red cells	4e-20
GCST90002405_156	Reticulocyte count	1e-18
GCST90011898_146	Alanine aminotransferase levels	1e-16
GCST004628_84	Immature fraction of reticulocytes	1e-15
GCST90002387_7	Immature fraction of reticulocytes	1e-12
GCST90002385_299	High light scatter reticulocyte count	6e-11
GCST011352_9	Alanine aminotransferase levels	2e-10
GCST90002405_155	Reticulocyte count	3e-10
GCST90002386_593	High light scatter reticulocyte percentage of red cells	4e-10
GCST007267_227	Systolic blood pressure	7e-10
GCST004612_205	High light scatter reticulocyte percentage of red cells	2e-9
GCST90013407_8	Liver enzyme levels (gamma-glutamyl transferase)	3e-9
GCST004611_40	High light scatter reticulocyte count	4e-9
GCST90002406_30	Reticulocyte fraction of red cells	5e-9
GCST90002407_651	White blood cell count	5e-9
GCST005998_21	Alanine transaminase levels	2e-8
GCST90011900_84	Serum alkaline phosphatase levels	2e-8

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0006335	systolic blood pressure
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
C564609	Deafness, Autosomal Recessive *(supp.)*
C563669	Deafness, Autosomal Recessive 68 *(supp.)*
C580334	Nonsyndromic Deafness *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2363041 (PROTEIN FAMILY), CHEMBL2955 (SINGLE PROTEIN), CHEMBL3430884 (PROTEIN COMPLEX)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes S1PR2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

3 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
FINGOLIMOD HYDROCHLORIDE	Sphingosine 1-phosphate receptor	5	4
FINGOLIMOD LAURYL SULFATE	Sphingosine 1-phosphate receptor	5	4
AMISELIMOD HYDROCHLORIDE	Sphingosine 1-phosphate receptor	5	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,710 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3707247	OZANIMOD	4	1,710

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Lysophospholipid (S1P) receptors

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
compound 16 [PMID: 26794040]	Antagonist	8.09	pIC50
JTE-013	Antagonist	7.77	pIC50
sphingosine 1-phosphate	Agonist	7.69	pKd
fingolimod-phosphate	Agonist	7.46	pEC50
CYM-5478	Agonist	6.92	pEC50
CYM5520	Agonist	6.32	pEC50
AUY954	Agonist	5.0	pEC50
ozanimod	Agonist	5.0	pEC50
compound 43 [PMID: 26751273]	Agonist	4.5	pEC50

Binding affinities (BindingDB)

485 measured of 732 human assays (734 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
[(2S)-2-amino-3-hydroxy-2-[2-(4-octylphenyl)ethyl]propoxy]phosphonic acid	EC50	0.006 nM
(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propyl dihydrogen phosphate	EC50	0.018 nM
(2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate	EC50	0.027 nM
CHEMBL4093489	EC50	0.027 nM
3-(4-(5-(3-cyano-4-(1,1,1-trifluoropropan-2-yloxy)phenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.03 nM
CHEMBL4874736	IC50	0.032 nM
CHEMBL3358955	EC50	0.041 nM
3-(4-(5-(4-(S)-sec-butoxy-3-cyanophenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.07 nM
2-amino-3-hydroxy-2-((R)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propyl dihydrogen phosphate	EC50	0.077 nM
3-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)propanoic acid	EC50	0.08 nM
3-(4-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-3-methylphenyl)propanoic acid	EC50	0.08 nM
[(1S,3R)-3-Amino-1-hydroxy-5-(4-octyl-phenyl)-pentyl]-phosphonic acid	IC50	0.1 nM
3-(4-(5-(3-cyano-4-(1,1,1,3,3,3-hexafluoropropan-2-yloxy)phenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.1 nM
3-(4-(5-(5-chloro-6-(1,1,1-trifluoropropan-2-yloxy)pyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.1 nM
3-(4-(5-(3-cyano-4-(2,2,2-trifluoroethoxy)phenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.11 nM
CHEMBL3359520	EC50	0.13 nM
[(2R)-2-amino-3-hydroxy-2-[2-(4-octylphenyl)ethyl]propoxy]phosphonic acid	EC50	0.14 nM
CHEMBL3359519	EC50	0.15 nM
3-(4-(5-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.15 nM
[3-Amino-1-hydroxy-5-(4-octyl-phenyl)-pentyl]-phosphonic acid	IC50	0.16 nM
{2-[5-(4-Nonyl-phenyl)-pyrrolidin-2-yl]-ethyl}-phosphonic acid	IC50	0.16 nM
[(1S,3S)-3-(4-Nonyl-benzylamino)-cyclohexyl]-phosphonic acid	IC50	0.16 nM
1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid	EC50	0.2 nM
3-(4-(5-(4-isopropoxy-3-methylphenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.2 nM
2-amino-2-({[dihydroxy(oxido)–phosphanyl]oxy}methyl)-4-(4-octylphenyl)butan-1-ol	IC50	0.28 nM
Phosphoric acid mono-[1-amino-1-hydroxymethyl-3-(4-octyl-phenyl)-propyl] ester	IC50	0.3 nM
CHEMBL4864274	IC50	0.3 nM
[1-(4-Nonyl-benzyl)-pyrrolidin-3-yl]-phosphonic acid	IC50	0.33 nM
3-(4-(5-(4-ethoxy-3-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.4 nM
CHEMBL4877932	IC50	0.43 nM
1-[4-(4-Phenyl-5-trifluoromethyl-thiophen-2-ylmethoxy)-benzyl]-azetidine-3-carboxylic acid	EC50	0.5 nM
CHEMBL3798837	EC50	0.5 nM
3-(4-(5-(4-cyclohexylphenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.5 nM
1-[(4-{5-[4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	0.6 nM
CHEMBL4850513	IC50	0.61 nM
FTY720-phosphate, rac-2	EC50	0.7 nM
(+/-)-2-(cis-5-(4-(5-(4-cyclohexylphenyl)-1,2,4-oxadiazol-3-yl)phenyl)pyrrolidin-2-yl)acetic acid	IC50	0.7 nM
3-(4-(5-(5-chloro-6-isopropoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.7 nM
Phosphoric acid mono-[2-amino-4-(4-octyl-phenyl)-butyl] ester	IC50	0.76 nM
CHEMBL4847056	IC50	0.77 nM
1-(3-methyl-4-((4-phenyl-5-(trifluoromethyl)thiophen-2-yl)methoxy)benzyl)azetidine-3-carboxylic acid	EC50	0.8 nM
(+/-)-2-(cis-5-(4-(5-(4-((S)-3,3-difluorocyclopentyl)phenyl)-1,2,4-oxadiazol-3-yl)phenyl)pyrrolidin-2-yl)acetic acid	IC50	0.8 nM
2-(trans-5-(4-(5-(4-((R)-3,3-difluorocyclopentyl)phenyl)-1,2,4-oxadiazol-3-yl)phenyl)pyrrolidin-3-yl)acetic acid	IC50	0.8 nM
CHEMBL4852127	IC50	0.8 nM
(S)-2-amino-4-(4-(heptyloxy)phenyl)-2-methylbutyl dihydrogen phosphate	EC50	0.85 nM
3-(4-(5-(5-(1,1-difluoro-2-methylpropyl)pyridin-2-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	0.9 nM
2-(trans-5-(4-(5-(4-cyclopentylphenyl)-1,2,4-oxadiazol-3-yl)phenyl)pyrrolidin-3-yl)acetic acid	IC50	1 nM
CHEMBL4871014	IC50	1 nM
[3-(10-Phenyl-decylamino)-propyl]-phosphonic acid	IC50	1.1 nM
3-(4-(5-(4-isopropoxy-3-methoxyphenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoic acid	EC50	1.1 nM

ChEMBL bioactivities

674 potent at pChembl≥5 of 792 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.49	IC50	0.032	nM	CHEMBL4874736
9.64	IC50	0.23	nM	CHEMBL225155
9.52	IC50	0.3	nM	CHEMBL4864274
9.49	IC50	0.32	nM	CHEMBL4874736
9.46	IC50	0.35	nM	CHEMBL225155
9.37	IC50	0.43	nM	CHEMBL4877932
9.31	Kd	0.49	nM	CHEMBL5172220
9.21	IC50	0.61	nM	CHEMBL4850513
9.20	Kd	0.63	nM	CHEMBL5193759
9.16	Kd	0.69	nM	CHEMBL5206290
9.15	IC50	0.7	nM	CHEMBL118860
9.15	EC50	0.7	nM	CHEMBL225155
9.14	Kd	0.73	nM	CHEMBL5208524
9.11	IC50	0.77	nM	CHEMBL4847056
9.11	IC50	0.77	nM	CHEMBL114606
9.10	IC50	0.8	nM	CHEMBL117130
9.10	IC50	0.8	nM	CHEMBL119440
9.10	IC50	0.8	nM	CHEMBL4852127
9.06	Kd	0.88	nM	CHEMBL5181599
9.05	Kd	0.89	nM	CHEMBL5206026
9.01	Kd	0.98	nM	CHEMBL3401388
9.00	IC50	1	nM	CHEMBL119116
8.94	Kd	1.15	nM	CHEMBL5201190
8.92	IC50	1.2	nM	CHEMBL5755435
8.89	EC50	1.3	nM	CHEMBL225155
8.89	IC50	1.3	nM	CHEMBL4874151
8.89	IC50	1.3	nM	CHEMBL5076031
8.85	IC50	1.4	nM	CHEMBL119382
8.82	IC50	1.5	nM	CHEMBL441826
8.77	IC50	1.7	nM	CHEMBL119413
8.77	IC50	1.7	nM	CHEMBL333335
8.74	IC50	1.8	nM	CHEMBL323617
8.74	IC50	1.8	nM	CHEMBL331054
8.74	IC50	1.8	nM	CHEMBL432067
8.72	IC50	1.9	nM	CHEMBL118815
8.70	IC50	2	nM	CHEMBL119873
8.68	IC50	2.1	nM	CHEMBL4860509
8.68	IC50	2.1	nM	CHEMBL5082556
8.66	EC50	2.2	nM	CHEMBL225155
8.65	IC50	2.25	nM	CHEMBL4868016
8.64	IC50	2.3	nM	CHEMBL3703203
8.59	IC50	2.6	nM	CHEMBL116981
8.59	IC50	2.6	nM	CHEMBL5192525
8.54	IC50	2.9	nM	CHEMBL119354
8.54	EC50	2.9	nM	CHEMBL225155
8.52	IC50	3	nM	CHEMBL332667
8.52	IC50	3	nM	CHEMBL3401386
8.52	IC50	3	nM	CHEMBL3703198
8.51	IC50	3.1	nM	CHEMBL4877928
8.49	IC50	3.2	nM	CHEMBL5082556

PubChem BioAssay actives

493 with measured affinity, of 1172 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
1-(2-chloro-6-ethoxy-4-pyridinyl)-3-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]methyl]urea	1776576: Antagonist activity at recombinant human S1P2 receptor in HFL1 cells assessed as inhibition of EC80 S1P-induced IL8 release incubated for 16 to 24 hrs in absence of HSA by ELISA	ic50	<0.0001	uM
[(E,2S,3R)-2-amino-3-hydroxyoctadec-4-enyl] dihydrogen phosphate	204174: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 5 expressed on CHO cell membranes	ic50	0.0002	uM
1-(3,5-dichlorophenyl)-3-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]methyl]urea	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0003	uM
5,6-dichloro-N-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]methyl]-1H-benzimidazol-2-amine	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0004	uM
4-(cyclohexylmethyl)-N-[3-(4-fluorophenoxy)-5-[4-(methylcarbamoyl)phenoxy]phenyl]piperazine-1-carboxamide	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0005	uM
4,6-dichloro-N-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]methyl]-1H-indole-2-carboxamide	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0006	uM
4-(2-ethylbutylamino)-N-[3-(4-fluorophenoxy)-5-pyridin-4-yloxyphenyl]piperidine-1-carboxamide	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0006	uM
3-[(4-nonylphenyl)methylamino]propylphosphonic acid	204171: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0007	uM
4-(2-ethylbutyl)-N-[3-(4-fluorophenoxy)-5-[4-(4-methylpiperazine-1-carbonyl)phenoxy]phenyl]piperazine-1-carboxamide	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0007	uM
4-(2-ethylbutyl)-N-[3-(4-fluorophenoxy)-5-[4-(methylcarbamoyl)phenoxy]phenyl]piperazine-1-carboxamide	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0007	uM
3-[(3,5-dimethyl-4-octoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0008	uM
1-(2,6-dichloro-4-pyridinyl)-3-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]methyl]urea	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0008	uM
1-(2,6-dichloro-4-pyridinyl)-3-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]amino]urea	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0008	uM
[2-amino-1-hydroxy-4-(4-octylphenyl)butan-2-yl] dihydrogen phosphate	204171: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0008	uM
[2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate	204174: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 5 expressed on CHO cell membranes	ic50	0.0008	uM
4-(2-ethylbutyl)-N-[3-(4-fluorophenoxy)-5-pyridin-4-yloxyphenyl]piperazine-1-carboxamide	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0009	uM
4-[3-[[4-(2-ethylbutyl)piperazine-1-carbonyl]amino]-5-(4-fluorophenoxy)phenoxy]benzoic acid	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0009	uM
3-[(3,5-dichloro-4-octoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0010	uM
4-(2-ethylbutyl)-N-[3-(4-fluorophenoxy)-5-pyridin-4-yloxyphenyl]-4-hydroxypiperidine-1-carboxamide	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0010	uM
tert-butyl 4-[[3-(4-fluorophenoxy)-5-[4-(methylcarbamoyl)phenoxy]phenyl]carbamoyl]piperazine-1-carboxylate	1848143: Binding affinity to S1PR2 (unknown origin) assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0011	uM
2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxocinnolin-3-yl]propanoic acid	1823899: Antagonist activity at human S1P2 in HFL1 cells assessed as inhibition of EC80 S1P-induced IL8 release incubated for 16 to 24 hrs by ELISA	ic50	0.0013	uM
4,6-dichloro-N-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0013	uM
3-[[4-(2-heptyltetrazol-5-yl)phenyl]methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0014	uM
3-[(3-bromo-4-decoxy-5-methoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0015	uM
3-[(3-chloro-4-octoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0017	uM
3-[(4-nonoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0017	uM
[2-amino-4-(4-octylphenyl)butyl] dihydrogen phosphate	204174: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 5 expressed on CHO cell membranes	ic50	0.0018	uM
3-[(3-methyl-4-octoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0018	uM
3-[[4-(5-heptyl-1,2,4-oxadiazol-3-yl)phenyl]methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0018	uM
3-[(3-bromo-5-methoxy-4-undecoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0019	uM
3-[(3-fluoro-4-octoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0020	uM
(2S)-2-[1-[[7-chloro-6-(cyclopropylmethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxocinnolin-3-yl]propanoic acid	1823899: Antagonist activity at human S1P2 in HFL1 cells assessed as inhibition of EC80 S1P-induced IL8 release incubated for 16 to 24 hrs by ELISA	ic50	0.0021	uM
ethyl 6-[2-[(2,6-dichloro-4-pyridinyl)carbamoyl]hydrazinyl]-4-methylpyridine-2-carboxylate	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0021	uM
6-chloro-N-[[5-(1,3-dimethylpyrazol-4-yl)-4-methyl-2-pyridinyl]methyl]-4-ethoxy-1H-imidazo[4,5-c]pyridin-2-amine	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0022	uM
2-[4-[3-(4-fluorophenoxy)-5-[[4-hydroxy-4-(2-methylpropyl)piperidine-1-carbonyl]amino]phenoxy]phenyl]-2-methylpropanoic acid	1275513: Antagonist activity at S1P2 receptor (unknown origin) expressed in CHO cells assessed as inhibition of S1P-induced increase in intracellular calcium ion concentration by Fura-2AM based fluorescence analysis	ic50	0.0023	uM
3-[[4-(4-hexylphenyl)phenyl]methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0026	uM
N-(5-chloro-2,4-dimethoxyphenyl)-2-[3-[2-(4-hydroxyanilino)-2-oxoethyl]-2,4-dioxoquinazolin-1-yl]acetamide	1853948: Displacement of [32P]S1P from human recombinant S1PR2 incubated for 60 mins by competitive binding assay based scintillation counter	ic50	0.0026	uM
3-[(3-bromo-4-octoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0029	uM
3-[(3,5-dibromo-4-octoxyphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0030	uM
4-(2-ethylbutyl)-N-[3-(4-fluorophenoxy)-5-[4-(methylcarbamoyl)phenoxy]phenyl]-4-hydroxypiperidine-1-carboxamide	1193526: Displacement of [33P]-S1P from human S1P2 receptor expressed in CHOK1 cells after 60 mins by scintillation counting analysis	ic50	0.0030	uM
1-(2,6-dichloro-4-pyridinyl)-3-[[4-methyl-6-(1-methylpyrazol-4-yl)-2-pyridinyl]amino]urea	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0031	uM
(2R)-2-[4-[[6-chloro-5-(cyclopropylmethoxy)indazol-2-yl]methyl]-1-oxophthalazin-2-yl]propanoic acid	1823893: Antagonist activity at human S1P2 receptor expressed in CHO cells assessed as inhibition of calcium flux	ic50	0.0032	uM
2-[1-[[6-(cyclopropylmethoxy)-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxocinnolin-3-yl]propanoic acid	1823893: Antagonist activity at human S1P2 receptor expressed in CHO cells assessed as inhibition of calcium flux	ic50	0.0034	uM
1-(2,6-dichloro-4-pyridinyl)-3-[[4-methyl-5-(1-methylpyrazol-4-yl)-2-pyridinyl]amino]urea	1776574: Antagonist activity at recombinant human S1P2 receptor expressed in human CHO cells assessed as EC80 S1P-induced activation incubated for 4 hrs in presence of [35S]GTPgammaS by Topcount reader	ic50	0.0034	uM
[(Z)-2-amino-3-hydroxyoctadec-4-enyl] dihydrogen phosphate	1798300: [32P] S1P Binding Assay from Article 10.1016/j.bmc.2004.10.008: “Asymmetric synthesis and biological evaluation of the enantiomeric isomers of the immunosuppressive FTY720-phosphate.”	ki	0.0034	uM
2-chloro-4-[3-(4-fluorophenoxy)-5-[[4-hydroxy-4-(2-methylpropyl)piperidine-1-carbonyl]amino]phenoxy]benzoic acid	1275513: Antagonist activity at S1P2 receptor (unknown origin) expressed in CHO cells assessed as inhibition of S1P-induced increase in intracellular calcium ion concentration by Fura-2AM based fluorescence analysis	ic50	0.0036	uM
N-[3-(4-carbamoylphenoxy)-5-(4-fluorophenoxy)phenyl]-4-(2-ethylbutyl)-4-hydroxypiperidine-1-carboxamide	1193526: Displacement of [33P]-S1P from human S1P2 receptor expressed in CHOK1 cells after 60 mins by scintillation counting analysis	ic50	0.0037	uM
3-[(3-bromo-5-methoxy-4-nonoxyphenyl)methylamino]propylphosphonic acid	204173: Binding affinity towards human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0039	uM
3-[(4-nonanoylphenyl)methylamino]propylphosphonic acid	204172: Binding affinity to human sphingosine 1-phosphate receptor 5 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0040	uM
4-[3-(4-fluorophenoxy)-5-[[4-hydroxy-4-(2-methylpropyl)piperidine-1-carbonyl]amino]phenoxy]benzoic acid	1275513: Antagonist activity at S1P2 receptor (unknown origin) expressed in CHO cells assessed as inhibition of S1P-induced increase in intracellular calcium ion concentration by Fura-2AM based fluorescence analysis	ic50	0.0040	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sphingosine 1-phosphate	decreases reaction, increases expression, increases uptake	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects cotreatment, affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Decitabine	affects cotreatment, affects expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases expression	1
Cantharidin	increases expression	1
Diazinon	increases methylation	1
Estradiol	increases expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Taurocholic Acid	increases uptake, increases expression, increases reaction, increases phosphorylation, increases activity	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

147 unique, capped per target: 78 functional, 69 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1051868	Functional	Ratio of agonistic EC50 for S1P to compound for human S1P2 receptor by [35S]GTPgammaS binding assay	Synthesis and biological evaluation of sphingosine kinase substrates as sphingosine-1-phosphate receptor prodrugs. — *Bioorg Med Chem*
CHEMBL1111161	Binding	Displacement of [33P]S1P from human recombinant S1P2 receptor expressed in HEK cells by scintillation counting	2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. — *J Med Chem*

Cellosaurus cell lines

5 cell lines: 2 spontaneously immortalized cell line, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9R7	Ubigene HEK293 S1PR2 KO	Transformed cell line	Female
CVCL_KA68	CHO-K1/EDG5/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KW96	PathHunter CHO-K1 EDG5 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA24	PathHunter U2OS EDG5 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZK38	Tango EDG5-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

1 trials:

NCT	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for S1PR2 across ~30M SureChEMBL compounds — explore on Sugi Predict.