S1PR3

Summary

S1PR3 (sphingosine-1-phosphate receptor 3, HGNC:3167) is a protein-coding gene on chromosome 9q22.1, encoding Sphingosine 1-phosphate receptor 3 (Q99500). Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P).

This gene encodes a member of the EDG family of receptors, which are G protein-coupled receptors. This protein has been identified as a functional receptor for sphingosine 1-phosphate and likely contributes to the regulation of angiogenesis and vascular endothelial cell function.

Source: NCBI Gene 1903 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 62 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005226

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3167
Approved symbol	S1PR3
Name	sphingosine-1-phosphate receptor 3
Location	9q22.1
Locus type	gene with protein product
Status	Approved
Aliases	EDG-3, FLJ37523, bA791O21.3
Ensembl gene	ENSG00000213694
Ensembl biotype	protein_coding
OMIM	601965
Entrez	1903

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000334490, ENST00000358157, ENST00000375846, ENST00000375850, ENST00000648341, ENST00000887789, ENST00000887792, ENST00000887793, ENST00000968554, ENST00000968555, ENST00000968556, ENST00000968557

RefSeq mRNA: 2 — MANE Select: NM_005226 NM_001395848, NM_005226

CCDS: CCDS6680

Canonical transcript exons

ENST00000358157 — 2 exons

Exon	Start	End
ENSE00001331415	89001054	89005155
ENSE00001407961	88991468	88991695

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7330 / max 183.3777, expressed in 1346 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97276	11.7330	1346

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	97.78	gold quality
decidua	UBERON:0002450	95.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.87	gold quality
lower esophagus	UBERON:0013473	95.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.24	gold quality
ventricular zone	UBERON:0003053	94.88	gold quality
heart right ventricle	UBERON:0002080	94.77	gold quality
right coronary artery	UBERON:0001625	94.66	gold quality
left coronary artery	UBERON:0001626	94.46	gold quality
coronary artery	UBERON:0001621	94.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.16	gold quality
cauda epididymis	UBERON:0004360	93.29	gold quality
descending thoracic aorta	UBERON:0002345	93.14	gold quality
superficial temporal artery	UBERON:0001614	93.10	gold quality
thoracic aorta	UBERON:0001515	92.96	gold quality
stromal cell of endometrium	CL:0002255	92.95	gold quality
myocardium	UBERON:0002349	92.82	gold quality
ascending aorta	UBERON:0001496	92.72	gold quality
aorta	UBERON:0000947	92.57	gold quality
popliteal artery	UBERON:0002250	92.33	gold quality
tibial artery	UBERON:0007610	92.29	gold quality
mucosa of stomach	UBERON:0001199	91.79	gold quality
metanephros	UBERON:0000081	91.66	gold quality
synovial joint	UBERON:0002217	91.63	gold quality
metanephros cortex	UBERON:0010533	91.51	gold quality
placenta	UBERON:0001987	91.29	gold quality
left uterine tube	UBERON:0001303	90.85	gold quality
tibia	UBERON:0000979	90.70	gold quality
smooth muscle tissue	UBERON:0001135	89.40	gold quality
pericardium	UBERON:0002407	89.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	46.93
E-ANND-3	yes	10.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting S1PR3, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-2110	99.96	66.68	1930
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-6778-3P	99.96	67.29	2693
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3140-3P	99.88	68.47	2069

Literature-anchored findings (GeneRIF, showing 40)

• activates Rho family G proteins and cell motility (PMID:11915348)
• a 9-amino acid peptide (KRX-725), derived from the second intracellular loop of S1P3 (EDG3) mimics sphingosine 1-phosphate (S1P) by triggering a Gi-dependent mitogen-activated protein kinase kinase and extracellular signal-regulated kinase signal. (PMID:12763936)
• S1P(3) function is not subject to conventional regulation by GRK phosphorylation (PMID:15894172)
• Expression of the sphingosine 1 phosphate receptor in primary endothelial cells is both sufficient and necessary for the expression of Akt3. (PMID:16527273)
• Sphingosine 1-phosphate-induced inflammatory response genes expression is mediated through S1P(1) and S1P(3) (PMID:17331465)
• Reults describe the role of mu opioid receptors and S1P3 transactivation in the attenuation of vascular permeability by methylnaltrexone. (PMID:17395891)
• Cytosolic phospholipase A2alpha activation induced by S1P is mediated by the S1P3 receptor in lung epithelial cells.( (PMID:18502815)
• Results suggest that S1PR3 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 synoviocyte migration, cytokine/chemokine production, and cell survival. (PMID:18658144)
• Report different response patterns of several ligands at the sphingosine-1-phosphate receptor subtype 3 (S1P(3)). (PMID:19309361)
• IGFBP-3 in MCF-10A cells requires SphK1 activity and S1P1/S1P3, suggesting that S1P, the product of SphK activity and ligand for S1P1 and S1P3 (PMID:19633297)
• amplification of SHC3 and EDG3 genes suggests that the two proteins co-operate and are important for ependymomas in vivo. (PMID:19748727)
• this study demonstrated that reactive astrocytes in MS lesions and cultured under proinflammatory conditions strongly enhance expression of S1P receptors 1 and 3. (PMID:20648639)
• These results support a model in which the interaction between sphingosine kinase 1, sphingosine 1-phosphate receptors 1 and/or 3, and ERK-1/2 might drive breast cancer progression (PMID:20889557)
• These results suggest a potential role for HDL and S1P receptors in the pathogenesis of prostate cancer. (PMID:20979115)
• The follicular fluid-HDL-associated S1P promotes granulosa lutein cell migration via S1PR3 and RAC1 activation. This may represent a novel mechanism contributing to the development of the corpus luteum. (PMID:20980685)
• 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)
• S1P regulates MMP-9 induction and invasiveness through coupling of S1P3 and G(alphaq) in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion. (PMID:21652634)
• These data have identified an additional function regulated by S1P/S1PR1,3 axis involving migration and fibrogenic activation of hepatic stellate cells. (PMID:21660960)
• S1PR3 was higher in iliac-femoral arteries compared with carotid arteries. (PMID:22308044)
• Suggest that the enhanced S1P3-EGFR signaling axis may contribute to the tumorigenesis or progression of lung adenocarcinomas. (PMID:22344462)
• abdominal aortic aneurysms have down-regulation of the S1P2 protein with simultaneous up-regulation of the S1P3 protein, but not S1P1 (PMID:22547907)
• However, growing evidence strongly suggests that the assessment of Sphingosine-1-phosphate receptor 1/3 (S1P1/3) own advantages over present measurements in predicting the risk of developing diabetic cardiovascular diseases. (PMID:22595806)
• S1PR3 is nitrated on specific tyrosine residues and released as endothelial cell microparticles during acute lung injury. (PMID:22771388)
• 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)
• Inhibition of S1P3 receptors prevented E2-induced activation of Cdc42, supporting the important role of the S1P receptor in E2 signaling. (PMID:23142484)
• S1P3 receptors are detected in virtually all neurons in dorsal root ganglion and mediate pain behavior. (PMID:23392686)
• key role of Sphk1, S1PR1 and S1PR3 in angiogenesis underlying the liver fibrosis process (PMID:23466305)
• S1PR agonists are pro-fibrotic via S1P2R and S1P3R stimulation using Smad-independent pathways. (PMID:23589284)
• associations were found for 2 promoter SNPs across 2 European descent samples supporting association of alleles -1899G and -1785C with decreased risk for sepsis-associated acute respiratory distress syndrome (ARDS); alleles reduced transcription factor binding to S1PR3 promoter and S1PR3 promoter activity; associated with lower plasma S1PR3 protein in ARDS patients (PMID:23911438)
• Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis. (PMID:23918395)
• we provide evidences that S1PR1/3, but not S1PR2, negatively regulate the expression of collagen in hMSCs using cellular and molecular approaches in vitro (PMID:24038457)
• a novel signaling axis, i.e., ROCK-JNK-ETS-1-CD44 pathway, which plays an essential role in the S1P3-regulated chemotactic response. (PMID:24064218)
• 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)
• Stimulation with sphingosine-1-phosphate enhances cancer stem cells via S1PR3 and subsequent Notch1 activation. (PMID:25254944)
• S1pr3 promotes leukocyte rolling by mobilization of endothelial P-selectin. (PMID:25832730)
• TRPC1 functions as a major regulator of S1P3 and VEGFR2 expression. (PMID:25971967)
• The S1P1,3 activation results in Akt phosphorylation and subsequent activation of eNOS via phosphorylation at serine(1177) and dephosphorylation at threonine(495). (PMID:27282481)
• in breast cancer cells overexpression of S1P3 and its activation by S1P has pro-inflammatory and pro-metastatic potential by inducing COX-2 expression and PGE2 signaling via EP2 and EP4. (PMID:27616330)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	S1pr3	ENSMUSG00000067586
rattus_norvegicus	S1pr3	ENSRNOG00000014524

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), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Sphingosine 1-phosphate receptor 3 — Q99500 (reviewed: Q99500)

Alternative names: Endothelial differentiation G-protein coupled receptor 3, Sphingosine 1-phosphate receptor Edg-3

All UniProt accessions (1): Q99500

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 effect 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.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in all tissues, but most abundantly in heart, placenta, kidney, and liver.

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

RefSeq proteins (2): NP_001382777, NP_005217* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR004061	S1P_rcpt	Family
IPR004062	EDG3_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (43 total): helix 12, topological domain 8, transmembrane region 7, strand 5, turn 4, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, glycosylation site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
9W0H	X-RAY DIFFRACTION	3
9W0O	ELECTRON MICROSCOPY	3
7EW2	ELECTRON MICROSCOPY	3.1
7EW3	ELECTRON MICROSCOPY	3.1
7C4S	X-RAY DIFFRACTION	3.2
7EW4	ELECTRON MICROSCOPY	3.2
9WP9	ELECTRON MICROSCOPY	3.25
9W0L	X-RAY DIFFRACTION	3.6
9L74	ELECTRON MICROSCOPY	3.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99500-F1	79.81	0.50

Antibody-complex structures (SAbDab): 5 — 7C4S, 7EW2, 7EW3, 7EW4, 9WP9

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): 326

Glycosylation sites (1): 15

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-419408	Lysosphingolipid and LPA receptors
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 246 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, WILLIAMS_ESR1_TARGETS_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_SPHINGOLIPID_MEDIATED_SIGNALING_PATHWAY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_DIFFERENTIATION, GOBP_INTERLEUKIN_1_PRODUCTION, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_DEVELOPMENT

GO Biological Process (12): inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), positive regulation of cytosolic calcium ion concentration (GO:0007204), Notch signaling pathway (GO:0007219), positive regulation of cell population proliferation (GO:0008284), anatomical structure morphogenesis (GO:0009653), regulation of interleukin-1 beta production (GO:0032651), negative regulation of establishment of endothelial barrier (GO:1903141), sphingosine-1-phosphate receptor signaling pathway (GO:0003376), signal transduction (GO:0007165)

GO Molecular Function (5): G protein-coupled receptor activity (GO:0004930), integrin binding (GO:0005178), lipid binding (GO:0008289), sphingosine-1-phosphate receptor activity (GO:0038036), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), presynapse (GO:0098793), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
G protein-coupled receptor signaling pathway	2
binding	2
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activator activity	1
adenylate cyclase inhibitor activity	1
regulation of biological quality	1
cell surface receptor signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
developmental process	1
anatomical structure development	1
interleukin-1 beta production	1
regulation of interleukin-1 production	1
establishment of endothelial barrier	1
negative regulation of endothelial cell development	1
regulation of establishment of endothelial barrier	1
sphingolipid mediated signaling pathway	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
sphingosine-1-phosphate receptor signaling pathway	1
bioactive lipid receptor activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
synapse	1

Protein interactions and networks

STRING

852 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
S1PR3	GNAQ	P50148	990
S1PR3	SPHK1	Q9NYA1	965
S1PR3	SPHK2	Q9NRA0	942
S1PR3	GNA12	Q03113	935
S1PR3	GNA13	Q14344	890
S1PR3	F2R	P25116	781
S1PR3	F2RL1	P55085	732
S1PR3	GNA15	P30679	708
S1PR3	SPNS2	Q8IVW8	669
S1PR3	PITRM1	Q5JRX3	669
S1PR3	PROCR	Q9UNN8	663
S1PR3	MFSD2B	A6NFX1	658
S1PR3	CERK	Q8TCT0	640
S1PR3	APOM	O95445	615
S1PR3	MAPK3	P27361	600

IntAct

22 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GYPB	S1PR3	psi-mi:“MI:0915”(physical association)	0.560
COMT	S1PR3	psi-mi:“MI:0915”(physical association)	0.560
ATP5F1B	SCAMP2	psi-mi:“MI:0914”(association)	0.530
S1PR3	ITGB4	psi-mi:“MI:0915”(physical association)	0.470
ITGB4	S1PR3	psi-mi:“MI:2364”(proximity)	0.470
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
PBXIP1	CEBPZOS	psi-mi:“MI:0914”(association)	0.350
S1PR3	STXBP3	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
COMT	S1PR3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): S1PR3 (Two-hybrid), GYPB (Two-hybrid), S1PR3 (Affinity Capture-MS), S1PR3 (Affinity Capture-MS), S1PR3 (Proximity Label-MS), S1PR3 (Proximity Label-MS), S1PR3 (Proximity Label-MS), S1PR3 (Proximity Label-MS), S1PR3 (Proximity Label-MS), S1PR3 (Proximity Label-MS), S1PR3 (Affinity Capture-Western), S1PR3 (Affinity Capture-MS), S1PR3 (Affinity Capture-MS), S1PR3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B4XF06, D4A3U0, O02777, O08530, O43194, O46635, P06199, P14842, P17200, P18599, P20272, P21453, P21554, P28223, P30372, P30544, P32240, P34979, P35363, P43114, P47746, P47936, P48303, P50128, P50129, P56971, Q333S9, Q5E9P3, Q5IS73, Q5U431, Q60F97, Q71SP5, Q75Z89, Q801M1, Q8BZL4, Q91178, Q91559, Q98894

Diamond homologs: E7EM37, O02213, O02777, O08530, O42384, O73810, O95136, O95977, P14416, P18089, P19020, P19328, P20272, P20288, P21453, P21554, P22270, P24628, P28286, P30545, P30728, P30951, P34972, P34973, P35412, P35462, P46089, P46095, P46628, P47746, P47752, P47936, P48303, P51651, P52592, P52702, P52703, P53453, P56971, P60026

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
“sphingosine 1-phosphate”	up-regulates	S1PR3	“chemical activation”
S1PR3	“up-regulates activity”	GNAS	binding
S1PR3	“up-regulates activity”	GNAL	binding
S1PR3	“up-regulates activity”	GNAI1	binding
S1PR3	“up-regulates activity”	GNAI3	binding
S1PR3	“up-regulates activity”	GNAO1	binding
S1PR3	“up-regulates activity”	GNAZ	binding
S1PR3	“up-regulates activity”	GNAQ	binding
S1PR3	“up-regulates activity”	GNA14	binding
“sphingosine 1-phosphate(1-)”	“up-regulates activity”	S1PR3	“chemical activation”
S1PR3	up-regulates	GNA13	binding
S1PR3	up-regulates	GNAI1	binding
“sphingosine 1-phosphate”	“up-regulates activity”	S1PR3	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	56
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
57292	GRCh38/hg38 9q21.33-22.2(chr9:87418580-90406012)x1	Pathogenic
1330172	GRCh37/hg19 9q21.33-22.2(chr9:90342469-93657932)x1	Likely pathogenic

SpliceAI

488 predictions. Top by Δscore:

Variant	Effect	Δscore
9:88991696:GTG:G	donor_loss	0.9900
9:88991697:T:A	donor_loss	0.9900
9:88991993:T:G	donor_gain	0.9900
9:88991692:GGAG:G	donor_gain	0.9800
9:88991693:G:GT	donor_gain	0.9800
9:88991694:AGG:A	donor_loss	0.9600
9:88991696:GTGA:G	donor_loss	0.9600
9:88991697:T:G	donor_loss	0.9600
9:88991992:G:GG	donor_gain	0.9600
9:88991693:GAG:G	donor_gain	0.9400
9:88991696:G:GG	donor_gain	0.9400
9:88991114:TTCC:T	donor_gain	0.9100
9:88991951:TGGAG:T	donor_gain	0.9000
9:89001048:T:A	acceptor_gain	0.8800
9:88991220:C:T	donor_gain	0.8700
9:89001045:T:A	acceptor_loss	0.8700
9:89001048:TGGCA:T	acceptor_loss	0.8700
9:89001049:GGCA:G	acceptor_loss	0.8700
9:89001050:GCAGG:G	acceptor_loss	0.8700
9:89001051:CAG:C	acceptor_loss	0.8700
9:89001052:A:G	acceptor_loss	0.8700
9:88991001:C:A	donor_gain	0.8600
9:88991955:G:GT	donor_gain	0.8600
9:89001053:GGA:G	acceptor_gain	0.8600
9:88991218:G:GT	donor_gain	0.8400
9:88991968:T:TA	donor_gain	0.8400
9:88991698:GAGAG:G	donor_loss	0.8100
9:88992201:G:GG	donor_gain	0.8100
9:89001052:A:AG	acceptor_gain	0.8100
9:89001053:G:GG	acceptor_gain	0.8100

AlphaMissense

2495 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:89001454:A:C	D85A	0.999
9:89001454:A:G	D85G	0.999
9:89001454:A:T	D85V	0.999
9:89001582:A:C	S128R	0.999
9:89001584:C:A	S128R	0.999
9:89001584:C:G	S128R	0.999
9:89002082:C:A	N294K	0.999
9:89002082:C:G	N294K	0.999
9:89001351:A:C	S51R	0.998
9:89001353:C:A	S51R	0.998
9:89001353:C:G	S51R	0.998
9:89001371:C:A	N57K	0.998
9:89001371:C:G	N57K	0.998
9:89001440:C:A	N80K	0.998
9:89001440:C:G	N80K	0.998
9:89001455:C:A	D85E	0.998
9:89001455:C:G	D85E	0.998
9:89001607:G:C	R136P	0.998
9:89001684:T:A	W162R	0.998
9:89001684:T:C	W162R	0.998
9:89001966:T:A	W256R	0.998
9:89001966:T:C	W256R	0.998
9:89002084:C:A	P295Q	0.998
9:89001442:T:C	L81P	0.997
9:89001574:C:A	S125Y	0.997
9:89001757:C:T	S186F	0.997
9:89001954:T:C	F252L	0.997
9:89001956:C:A	F252L	0.997
9:89001956:C:G	F252L	0.997
9:89002070:C:A	N290K	0.997

dbSNP variants (sampled 300 via entrez): RS1000206370 (9:88990360 A>G), RS1000214979 (9:88999549 G>T), RS1000229978 (9:88993651 T>A,G), RS1000487738 (9:89005536 T>C), RS1000530103 (9:88994659 G>A), RS1000541014 (9:89000865 T>A), RS1000541867 (9:88988911 A>G), RS1000600081 (9:88993319 T>C), RS1000615443 (9:88994601 C>A,T), RS1000663144 (9:88988926 C>T), RS1000734851 (9:88989299 T>A,G), RS1001049747 (9:88994828 A>C), RS1001077086 (9:89000400 G>A,T), RS1001633903 (9:89001477 A>C,G), RS1001638218 (9:88992229 G>T)

Disease associations

OMIM: gene MIM:601965 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001408_7	Response to statins (LDL cholesterol change)	7.000000e-07
GCST003472_19	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	3.000000e-06
GCST003472_21	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	1.000000e-06
GCST003472_9	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	3.000000e-06
GCST004609_3	Monocyte percentage of white cells	9.000000e-10
GCST005991_95	Platelet count	4.000000e-09
GCST006101_5	Cardiometabolic and hematological traits	2.000000e-21
GCST006192_44	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-09
GCST006995_2	Logical memory (delayed recall) in Alzheimer’s disease dementia	7.000000e-08
GCST007954_46	Glycated hemoglobin levels	3.000000e-14
GCST90002394_298	Monocyte percentage of white cells	7.000000e-13
GCST90016667_5	Spleen volume	3.000000e-23

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007804	LDL cholesterol change measurement
EFO:0007679	oppositional defiant disorder measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0004309	platelet count
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004874	memory performance
EFO:0004541	HbA1c measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2363041 (PROTEIN FAMILY), CHEMBL3430884 (PROTEIN COMPLEX), CHEMBL3892 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 19,794 (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
CHEMBL1096146	PONESIMOD	4	672
CHEMBL2336071	SIPONIMOD	4	1,508
CHEMBL314854	FINGOLIMOD	4	16,015
CHEMBL3707247	OZANIMOD	4	1,588
CHEMBL3806158	BMS-986104	1	11

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Lysophospholipid (S1P) receptors

Most potent curated ligand interactions (19 total), top 19:

Ligand	Action	Affinity	Parameter
sphingosine 1-phosphate	Agonist	9.64	pKd
AFD(R)	Agonist	9.4	pEC50
SPM-354	Antagonist	9.3	pA2
(S)-FTY720-phosphate	Agonist	8.51	pEC50
fingolimod-phosphate	Agonist	8.3	pIC50
VPC03090-P	Antagonist	7.29	pKi
TY-52156	Antagonist	6.96	pKi
VPC44116	Antagonist	6.52	pKi
VPC12249	Agonist	6.5	pEC50
ASP4058	Agonist	6.04	pEC50
mocravimod-phosphate	Partial agonist	6.0	pEC50
AUY954	Agonist	5.96	pEC50
VPC23019	Antagonist	5.93	pKi
ponesimod	Agonist	5.68	pIC50
siponimod	Agonist	5.3	pEC50
compound 43 [PMID: 26751273]	Agonist	5.1	pEC50
proximod	Agonist	5.0	pEC50
ozanimod	Agonist	5.0	pEC50
compound 26 [PMID: 16190743]	Agonist	4.9	pIC50

Binding affinities (BindingDB)

846 measured of 1402 human assays (1415 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
MLS000042779	EC50	0.0019 nM
1-[6-(4-ethoxy-3-methoxy-phenyl)-3-(methylthio)-6H-[1,2,4]triazino[5,6-d][3,1]benzoxazepin-7-yl]ethanone	EC50	0.00238 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
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-[2-methyl-6-(2-methylpropyl)-4-pyridinyl]-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.1 nM	US-9617250: Pyridin-4-yl derivatives
N-[(2S)-3-[4-[5-(2-cyclopentyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.1 nM	US-9617250: Pyridin-4-yl derivatives
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-(2-pentan-3-yl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.1 nM	US-9617250: Pyridin-4-yl derivatives
3-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)butanoic acid	EC50	0.12 nM
BDBM50165434	EC50	0.2 nM	US-9617250: Pyridin-4-yl derivatives
N-[(2S)-3-[4-[5-(2-cyclopentyl-6-methyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.2 nM	US-9617250: Pyridin-4-yl derivatives
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-[2-(2-methylpropyl)-4-pyridinyl]-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.2 nM	US-9617250: Pyridin-4-yl derivatives
(1S,2S)-2-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)cyclopropane-1-carboxylic acid	EC50	0.21 nM
2-methyl-3-(3-methyl-4-{5-[4-(propan-2-yloxy)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)propanoic acid	EC50	0.3 nM
N-[(2S)-3-[2-ethyl-4-[5-(2-ethyl-6-methyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.3 nM	US-9617250: Pyridin-4-yl derivatives
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-(2-propan-2-yl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.3 nM	US-9617250: Pyridin-4-yl derivatives
1-[[3-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-4H-chromeno[4,3-c][1,2]oxazol-7-yl]methyl]azetidine-3-carboxylic acid	EC50	0.32 nM	US-9216972: Tricyclic heterocyclic compounds
1-({4-[5-(4-cyclopentylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	0.4 nM
1-[(4-{5-[4-(3,3,3-trifluoropropyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	0.4 nM
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-(2-methyl-6-propyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.4 nM	US-9617250: Pyridin-4-yl derivatives
3-(5-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-6-methylpyridin-2-yl)propanoic acid	EC50	0.44 nM
(1S,2S)-2-(4-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-3-methylphenyl)cyclopropane-1-carboxylic acid	EC50	0.45 nM
1-[[3-[5-phenyl-4-(trifluoromethyl)-1,2-oxazol-3-yl]-4,5-dihydrobenzo[g][2,1]benzoxazol-7-yl]methyl]azetidine-3-carboxylic acid	EC50	0.59 nM	US-9216972: Tricyclic heterocyclic compounds
1-[(4-{5-[4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	0.6 nM
[(1R,3S)-1-amino-3-[(6S)-6-[2-(2-methoxyphenyl)ethyl]-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	0.6 nM	US-9522888: Substituted bicyclic compounds
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-(2-propyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	0.7 nM	US-9617250: Pyridin-4-yl derivatives
1-[[3-[4-(2-methylpropyl)-3-(trifluoromethyl)phenyl]-4,5-dihydrobenzo[g][2,1]benzoxazol-7-yl]methyl]azetidine-3-carboxylic acid	EC50	0.73 nM	US-9216972: Tricyclic heterocyclic compounds
1-[[3-[5-(2-methylpropyl)-4-(trifluoromethyl)-1,2-oxazol-3-yl]-4,5-dihydrobenzo[g][2,1]benzoxazol-7-yl]methyl]azetidine-3-carboxylic acid	EC50	0.74 nM	US-9216972: Tricyclic heterocyclic compounds
1-[8-fluoro-3-[3-phenyl-4-(trifluoromethyl)-1,2-oxazol-5-yl]-4,5-dihydrobenzo[g][2,1]benzoxazol-7-yl]azetidine-3-carboxylic acid	EC50	0.76 nM	US-9216972: Tricyclic heterocyclic compounds
1-{[4-(5-{4-[(1R)-3,3-difluorocyclopentyl]phenyl}-1,2,4-oxadiazol-3-yl)phenyl]methyl}azetidine-3-carboxylic acid	IC50	0.8 nM
(1S,2R)-2-(4-{5-[3-cyano-4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}-3-methylphenyl)cyclopropane-1-carboxylic acid	EC50	0.8 nM
N-[(3,4-difluorophenyl)methyl]-2-propan-2-yl-6-propan-2-yloxy-1-(pyridin-2-ylmethyl)indole-3-carboxamide	IC50	0.9 nM	US-8524917: 6-substituted indole-3-carboxylic acid amide compounds having sphingosine-1-phosphate (S1P) receptor antagonist biological activity
1-{[4-(5-{4-[(1S)-3,3-difluorocyclopentyl]phenyl}-1,2,4-oxadiazol-3-yl)phenyl]methyl}azetidine-3-carboxylic acid	IC50	0.9 nM
1-benzyl-N-[(3,4-difluorophenyl)methyl]-6-(2-methylpropoxy)-2-propan-2-ylindole-3-carboxamide	IC50	1.2 nM	US-8524917: 6-substituted indole-3-carboxylic acid amide compounds having sphingosine-1-phosphate (S1P) receptor antagonist biological activity
1-[[3-(4-propylphenyl)-4H-chromeno[4,3-c][1,2]oxazol-7-yl]methyl]azetidine-3-carboxylic acid	EC50	1.2 nM	US-9216972: Tricyclic heterocyclic compounds
{[(4Z)-2-amino-3-hydroxyoctadec-4-en-1-yl]oxy}phosphonic acid	KI	1.2 nM
[(1S,3S)-1-amino-3-[(6R)-6-(3-ethoxypropyl)-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate	EC50	1.2 nM	US-9522888: Substituted bicyclic compounds
1-[[3-(4-propylphenyl)-4H-chromeno[3,4-d][1,2]oxazol-7-yl]methyl]azetidine-3-carboxylic acid	EC50	1.3 nM	US-9216972: Tricyclic heterocyclic compounds
1-[(4-{5-[4-(2-methylbutan-2-yl)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	1.3 nM
1-({4-[5-(4-propylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	1.3 nM
1-({4-[5-(4-cyclohexylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	1.4 nM
N-(1-cyanocyclopropyl)-2-hydroxy-2-[3-[5-phenyl-4-(trifluoromethyl)-1,2-oxazol-3-yl]-4,5-dihydrobenzo[g][2,1]benzoxazol-7-yl]acetamide	EC50	1.7 nM	US-9216972: Tricyclic heterocyclic compounds
1-({4-[5-(4-phenylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	1.7 nM
1-[(4-{5-[4-(propan-2-yloxy)phenyl]-1,2,4-oxadiazol-3-yl}phenyl)methyl]azetidine-3-carboxylic acid	IC50	1.8 nM
N-[(2S)-3-[4-[5-(2-butyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	1.8 nM	US-9617250: Pyridin-4-yl derivatives
6-(cyclohexyl(cyclopropylmethyl)amino)-N-(2-methyl-4-sulfamoylphenyl)pyrimidine-4-carboxamide	EC50	2 nM	US-9150519: 6-amino-pyrimidine-4-carboxamide derivatives and related compounds which bind to the sphingosine 1-phosphate (S1P) receptor for the treatment of multiple sclerosis
[(2S)-2-amino-3-hydroxy-2-[2-(4-octylphenyl)ethyl]propoxy]phosphonic acid	KI	2.1 nM
N-[(2S)-3-[2-ethyl-4-[5-(2-ethyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	EC50	2.1 nM	US-9617250: Pyridin-4-yl derivatives
1-({4-[5-(4-cyclobutylphenyl)-1,2,4-oxadiazol-3-yl]phenyl}methyl)azetidine-3-carboxylic acid	IC50	2.2 nM
2-amino-2-[[4-[5-(3,4-dipropylphenyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydroindol-1-yl]methyl]propane-1,3-diol	EC50	2.4 nM	US-9181182: S1P receptors modulators
1-[[4-[[6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidine-4-carbonyl]amino]phenyl]methyl]azetidine-3-carboxylic acid	EC50	2.9 nM	US-9150519: 6-amino-pyrimidine-4-carboxamide derivatives and related compounds which bind to the sphingosine 1-phosphate (S1P) receptor for the treatment of multiple sclerosis

ChEMBL bioactivities

1979 potent at pChembl≥5 of 2074 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	IC50	0.04	nM	CHEMBL225155
10.00	EC50	0.1	nM	CHEMBL114606
9.87	EC50	0.134	nM	FTY720-P
9.82	EC50	0.15	nM	CHEMBL1089004
9.75	EC50	0.1778	nM	CHEMBL199791
9.70	EC50	0.2	nM	CHEMBL225155
9.67	EC50	0.215	nM	CHEMBL1091103
9.59	IC50	0.26	nM	CHEMBL225155
9.54	EC50	0.286	nM	CHEMBL1093686
9.44	IC50	0.36	nM	CHEMBL473156
9.40	IC50	0.4	nM	CHEMBL225155
9.35	EC50	0.449	nM	CHEMBL225155
9.18	IC50	0.66	nM	CHEMBL225155
9.15	IC50	0.71	nM	CHEMBL432067
9.15	EC50	0.7	nM	CHEMBL225155
9.05	IC50	0.9	nM	CHEMBL3655496
9.04	IC50	0.91	nM	CHEMBL119349
9.04	IC50	0.92	nM	CHEMBL225155
8.96	IC50	1.1	nM	CHEMBL333335
8.96	EC50	1.1	nM	CHEMBL225155
8.92	IC50	1.2	nM	CHEMBL119873
8.92	EC50	1.2	nM	CHEMBL3121986
8.92	EC50	1.2	nM	CHEMBL225155
8.92	IC50	1.2	nM	CHEMBL3655408
8.86	EC50	1.38	nM	CHEMBL473238
8.85	EC50	1.4	nM	CHEMBL114606
8.85	EC50	1.4	nM	CHEMBL3799355
8.80	EC50	1.6	nM	CHEMBL225155
8.77	EC50	1.7	nM	CHEMBL190006
8.70	EC50	2	nM	CHEMBL114606
8.70	EC50	2	nM	FTY720-P
8.70	IC50	2	nM	CHEMBL117031
8.62	EC50	2.4	nM	CHEMBL225155
8.62	EC50	2.4	nM	CHEMBL3126589
8.60	EC50	2.5	nM	CHEMBL190006
8.57	IC50	2.7	nM	CHEMBL117973
8.57	IC50	2.7	nM	CHEMBL118860
8.57	IC50	2.7	nM	CHEMBL184879
8.57	IC50	2.7	nM	CHEMBL119256
8.55	IC50	2.8	nM	CHEMBL184879
8.55	IC50	2.8	nM	CHEMBL118265
8.52	EC50	3	nM	FTY720-P
8.52	EC50	3	nM	FINGOLIMOD
8.52	IC50	3	nM	CHEMBL3741414
8.52	IC50	3	nM	CHEMBL3655407
8.52	IC50	3	nM	CHEMBL3655411
8.52	IC50	3	nM	CHEMBL3659686
8.52	EC50	3	nM	CHEMBL225155
8.51	IC50	3.1	nM	CHEMBL118860
8.51	EC50	3.1	nM	FTY720-P

PubChem BioAssay actives

938 with measured affinity, of 2211 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
[(E,2S,3R)-2-amino-3-hydroxyoctadec-4-enyl] dihydrogen phosphate	204054: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 3 expressed on CHO cell membranes	ic50	<0.0001	uM
[(2S)-2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate	473718: Agonist activity at human S1P3 receptor assessed as effect on calcium mobilization by Gi dependent whole cell assay	ec50	0.0001	uM
[(2R)-2-amino-2-[(2R)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl]propyl] dihydrogen phosphate	473718: Agonist activity at human S1P3 receptor assessed as effect on calcium mobilization by Gi dependent whole cell assay	ec50	0.0001	uM
[2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate	284811: Activity at human S1P3 receptor expressed in HEK293T cells by [35S]GTP-gamma-S binding assay	ec50	0.0001	uM
[2-amino-3-hydroxy-2-[(2R)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl]propyl] dihydrogen phosphate	473718: Agonist activity at human S1P3 receptor assessed as effect on calcium mobilization by Gi dependent whole cell assay	ec50	0.0002	uM
[(E,2S,3R)-2-amino-3-hydroxypentadec-4-enyl] dihydrogen phosphate	258418: Binding potency at human S1P3 receptor by [35S]GTP-gamma-S binding assay	ec50	0.0002	uM
[(2R)-2-amino-2-[(2S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl]propyl] dihydrogen phosphate	473718: Agonist activity at human S1P3 receptor assessed as effect on calcium mobilization by Gi dependent whole cell assay	ec50	0.0003	uM
[(2S)-2-amino-2-methyl-3-oxo-3-[4-(5-phenylpentoxy)anilino]propyl] dihydrogen phosphate	351685: Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	ic50	0.0004	uM
[2-amino-4-(4-octylphenyl)butyl] dihydrogen phosphate	1474270: Displacement of [33P]-S1P from human S1P3 receptor expressed in CHO cell membranes	ic50	0.0007	uM
3-(10-phenyldecylamino)propylphosphonic acid	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0009	uM
3-[(4-nonoxyphenyl)methylamino]propylphosphonic acid	204052: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0011	uM
3-[(3-fluoro-4-octoxyphenyl)methylamino]propylphosphonic acid	204052: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0012	uM
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-(3,5,5-triethyl-6,7-dihydro-4H-2-benzothiophen-1-yl)-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	1071199: Agonist activity at human recombinant S1P3 receptor expressed in CHO cells assessed as membrane-bound 35S-GTPgammaS incubated 30 mins prior to substrate addition measured after 1 hr by topcount scintillation counting analysis	ec50	0.0012	uM
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-[3-[[methyl(2-methylpropyl)amino]methyl]-5-propan-2-ylphenyl]-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	1297733: Agonist activity at human recombinant S1PR3 expressed in CHO cell membranes assessed as [35S]GTPgammaS binding preincubated for 30 mins followed by [35S]GTPgammaS addition measured after 1 hr by topcount analysis	ec50	0.0014	uM
[(2S)-2-amino-2-methyl-3-oxo-3-[4-[3-(4-phenylphenyl)propoxy]anilino]propyl] dihydrogen phosphate	351689: Agonist activity at human S1P3 receptor assessed as stimulation of [35S]GTPgammaS binding	ec50	0.0014	uM
[(2R)-2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl] dihydrogen phosphate	305221: Activity at human recombinant S1P3 receptor expressed in CHO cells assessed as increase in calcium release by FLIPR assay	ec50	0.0017	uM
(3-amino-13-phenyltridecyl)phosphonic acid	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0020	uM
N-[(2S)-3-[4-[5-(2-cyclopentyl-6-ethyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	1073713: Agonist activity at human recombinant S1P3 receptor expressed in CHO cells incubated for 30 mins prior to [35S]-GTPgammaS addition measured after 1 hr by topcount scintillation counting analysis	ec50	0.0024	uM
3-[(4-octylphenyl)methylamino]propylphosphonic acid	1474270: Displacement of [33P]-S1P from human S1P3 receptor expressed in CHO cell membranes	ic50	0.0027	uM
3-[(4-nonylphenyl)methylamino]propylphosphonic acid	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0027	uM
3-(pentadecylamino)propylphosphonic acid	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0027	uM
2-[5-(4-nonylphenyl)pyrrolidin-2-yl]ethylphosphonic acid	241961: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 3 expressed on CHO cell membranes	ic50	0.0027	uM
3-(tridecylamino)propylphosphonic acid	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0028	uM
Fingolimod	1054254: Agonist activity at S1P3 receptor (unknown origin)	ec50	0.0030	uM
[(1R,3R)-1-amino-3-(4-octoxyphenyl)cyclopentyl]methyl dihydrogen phosphate	1264658: Displacement of [33P]S1P from S1P3 receptor (unknown origin) expressed in HEK cell membranes after 45 to 60 mins by scintillation counting based RLB method	ic50	0.0030	uM
N-[(2S)-3-[2-ethyl-6-methyl-4-[5-[3-[[methyl(2-methylpropyl)amino]methyl]-5-propylphenyl]-1,2,4-oxadiazol-3-yl]phenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	1297733: Agonist activity at human recombinant S1PR3 expressed in CHO cell membranes assessed as [35S]GTPgammaS binding preincubated for 30 mins followed by [35S]GTPgammaS addition measured after 1 hr by topcount analysis	ec50	0.0035	uM
3-(tetradecylamino)propylphosphonic acid	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0036	uM
[(2S)-2-amino-3-(2-fluoro-4-octoxyanilino)-2-methyl-3-oxopropyl] dihydrogen phosphate	392390: Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	ic50	0.0036	uM
N-[(2S)-3-[2-ethyl-4-[5-(2-ethyl-6-pentan-3-yl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	1073713: Agonist activity at human recombinant S1P3 receptor expressed in CHO cells incubated for 30 mins prior to [35S]-GTPgammaS addition measured after 1 hr by topcount scintillation counting analysis	ec50	0.0036	uM
1-[[4-[5-[4-(2-methylbutan-2-yl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic acid	255014: Concentration required for displacement of [33P]-labeled S1P from human sphingosine 1-phosphate receptor 3 expressed in CHO cells	ic50	0.0039	uM
[2-amino-4-[4-(2-fluoro-4-phenylmethoxyphenyl)phenyl]-2-(hydroxymethyl)butyl] dihydrogen phosphate	475241: Agonist activity at human S1P3 receptor expressed in CHO cells assessed as intracellular calcium mobilization	ec50	0.0041	uM
3-[2-(4-octylphenyl)ethylamino]propylphosphonic acid	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0043	uM
[(1S,3S)-3-[(4-nonylphenyl)methylamino]cyclohexyl]phosphonic acid	241961: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 3 expressed on CHO cell membranes	ic50	0.0047	uM
3-[(3-chloro-4-octoxyphenyl)methylamino]propylphosphonic acid	204052: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0049	uM
[2-amino-4-[4-(2-fluoro-4-phenylsulfanylphenyl)phenyl]-2-(hydroxymethyl)butyl] dihydrogen phosphate	475241: Agonist activity at human S1P3 receptor expressed in CHO cells assessed as intracellular calcium mobilization	ec50	0.0049	uM
[(E,2S,3R)-2-amino-3-hydroxy-15-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]pentadec-4-enyl] dihydrogen phosphate	258418: Binding potency at human S1P3 receptor by [35S]GTP-gamma-S binding assay	ec50	0.0050	uM
N-[(2S)-3-[4-[5-(2-cyclobutyl-6-ethyl-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide	1073713: Agonist activity at human recombinant S1P3 receptor expressed in CHO cells incubated for 30 mins prior to [35S]-GTPgammaS addition measured after 1 hr by topcount scintillation counting analysis	ec50	0.0050	uM
2-[(2R,5S)-5-tetradecylpyrrolidin-2-yl]ethylphosphonic acid	241961: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 3 expressed on CHO cell membranes	ic50	0.0052	uM
[(2R)-2-amino-2-[5-(4-octoxyphenyl)-1H-imidazol-2-yl]propyl] dihydrogen phosphate	392390: Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	ic50	0.0053	uM
[(2S)-2-amino-4-(4-heptoxyphenyl)-2-methylbutyl] dihydrogen phosphate	466804: Agonist activity at human S1P3 receptor expressed in CHO cells assessed as induction of [S35]GTPgammaS binding	ec50	0.0054	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	0.0054	uM
[(2R)-2-amino-2-[5-(3-fluoro-4-octoxyphenyl)-1H-imidazol-2-yl]propyl] dihydrogen phosphate	392390: Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	ic50	0.0058	uM
3-[2-[2-ethyl-4-[5-(3-ethyl-5,5-dimethyl-6,7-dihydro-4H-2-benzothiophen-1-yl)-1,2,4-oxadiazol-3-yl]-6-methylphenoxy]ethylamino]propanoic acid	1071199: Agonist activity at human recombinant S1P3 receptor expressed in CHO cells assessed as membrane-bound 35S-GTPgammaS incubated 30 mins prior to substrate addition measured after 1 hr by topcount scintillation counting analysis	ec50	0.0058	uM
[(2S)-2-amino-2-methyl-3-(4-octoxyanilino)-3-oxopropyl] dihydrogen phosphate	392390: Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	ic50	0.0059	uM
[(2S)-2-amino-3-(3-fluoro-4-octoxyanilino)-2-methyl-3-oxopropyl] dihydrogen phosphate	392390: Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	ic50	0.0059	uM
3-[(3-methyl-4-octoxyphenyl)methylamino]propylphosphonic acid	204052: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0060	uM
[(2R)-2-amino-2-[5-[4-(5-phenylpentoxy)phenyl]-1H-imidazol-2-yl]propyl] dihydrogen phosphate	351685: Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	ic50	0.0060	uM
[(2R)-2-amino-4-(4-heptoxyphenyl)-2-methylbutyl] dihydrogen phosphate	258418: Binding potency at human S1P3 receptor by [35S]GTP-gamma-S binding assay	ec50	0.0063	uM
[2-amino-1-hydroxy-4-(4-octylphenyl)butan-2-yl] dihydrogen phosphate	204051: Binding affinity to human sphingosine 1-phosphate receptor 3 expressed in CHO cells was determined by using [33P]-S1P as radioligand	ic50	0.0063	uM
[2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butoxy]-trihydroxyphosphanium	241961: Inhibition of [33P]-S1P binding to human Sphingosine 1-phosphate receptor 3 expressed on CHO cell membranes	ic50	0.0063	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	increases expression, increases reaction, affects cotreatment, affects expression, decreases expression	5
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	4
sphingosine 1-phosphate	decreases reaction, increases expression, affects reaction	3
Estradiol	affects binding, increases expression, decreases expression	3
Valproic Acid	decreases expression, increases expression, increases methylation	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Nickel	increases expression	2
Smoke	decreases expression, increases expression	2
1-Methyl-4-phenylpyridinium	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression	2
Simvastatin	increases expression, decreases expression	2
Genistein	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
VPC23019	decreases activity	1
daidzein	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
daidzin	affects cotreatment, decreases expression	1
o,p’-DDT	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	decreases expression	1
butylbenzyl phthalate	affects reaction, increases expression, increases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
propionic acid	increases expression	1
aflatoxin B2	decreases methylation	1

ChEMBL screening assays

225 unique, capped per target: 123 functional, 94 binding, 8 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3386601	Functional	Agonist activity at S1P2/3 receptor in HEK293 cells assessed as inhibition of forskolin-induced cAMP level after 1 hr by alphascreen immunoassay	The design and implementation of a generic lipopeptide scanning platform to enable the identification of ’locally acting’ agonists for the apelin receptor. — Bioorg Med Chem Lett
CHEMBL1029036	Binding	Displacement of [33P]sphingosine-1-phosphate from human S1P3 receptor	Synthesis and evaluation of alkoxy-phenylamides and alkoxy-phenylimidazoles as potent sphingosine-1-phosphate receptor subtype-1 agonists. — Bioorg Med Chem Lett
CHEMBL3876453	ADMET	Agonist activity at recombinant human S1PR3 expressed in CHO cell membranes assessed as [35S]GTP-gammaS binding measured after 1.5 hrs by TopCount scintillation counting method	A benzo[b]thiophene-based selective type 4 S1P receptor agonist. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 6 cancer cell line, 3 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7ZW	Ubigene A-549 S1PR3 KO	Cancer cell line	Male
CVCL_D9R8	Ubigene HEK293 S1PR3 KO	Transformed cell line	Female
CVCL_E0N6	Ubigene HeLa S1PR3 KO	Cancer cell line	Female
CVCL_E1K3	HyCyte HCT 116 KO-hS1PR3	Cancer cell line	Male
CVCL_KA18	RH7777/EDG3	Cancer cell line	Female
CVCL_KU53	CHO-K1 EDG3 Gq	Spontaneously immortalized cell line	Female
CVCL_KW94	PathHunter CHO-K1 EDG3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ46	PathHunter HEK 293 EDG3 beta-arrestin	Transformed cell line	Female
CVCL_LA23	PathHunter U2OS EDG3 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZI79	GeneBLAzer EDG3-Galpha15-NFAT-bla HEK 293T	Transformed cell line	Female

Clinical trials (associated diseases)

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