Protein / target

Sphingosine 1-phosphate receptor 2

S1PR2O95136Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
2
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

G protein-coupled peptide receptor activity

Primary system

Nervous system

Strongest disease association

deafness

Genetic evidence · score 0.71

Therapeutic maturity

Clinically validated target

3 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

3 approved · 2 in clinical development

2 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P) (PubMed:10617617, PubMed:25274307). S1P is a bioactive lysophospholipid that elicits diverse physiological effects on most types of cells and tissues (PubMed:10617617). When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis (PubMed:10617617). Receptor for the chemokine-like protein FAM19A5 (PubMed:29453251). Mediates the inhibitory effect of FAM19A5 on vascular smooth muscle cell proliferation and migration (By similarity). 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
Domains and Gene Ontology detail (18)

Gene Ontology

  • Ccytoplasm
  • Cglutamatergic synapse
  • Cplasma membrane
  • Cpresynapse
  • FG protein-coupled peptide receptor activity
  • FG protein-coupled receptor activity
  • FG protein-coupled receptor binding
  • Fintegrin binding
  • Flipid binding
  • Fsphingosine-1-phosphate receptor activity
  • Pactin cytoskeleton organization
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway

353 aa · 39 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

G protein-coupled signallingGOSynaptic signallingGOExcitatory neurotransmissionGOImmune signallingUniProt
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled peptide receptor activity
  • ·G protein-coupled receptor activity
  • ·G protein-coupled receptor binding
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway

Synaptic signalling

  • ·glutamatergic synapse
  • ·presynapse
  • ·regulation of postsynapse assembly

Excitatory neurotransmission

  • ·glutamatergic synapse

Immune signalling

  • ·Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P) (PubMed:10617617, PubMed…
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GNA13GNAQGNA12SPHK1GNAI2GNAI1GNB1GNAI3SPHK2APOMS1PR2

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Sphingosine 1-phosphate receptor agonist

Appears in clinical studies involving multiple sclerosis, relapsing-remitting multiple sclerosis, kidney transplant

Acts on a complex — shared with S1PR5, S1PR4, S1PR3 +1 more · 1 of 5 recorded protein targets

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

deafness0.71

Genetic · overall 0.53

hearing loss, autosomal recessive0.69

Genetic · overall 0.57

Non-syndromic genetic deafness0.61

Genetic literature · overall 0.39

nonsyndromic genetic hearing loss0.61

Genetic literature · overall 0.37

hypertensive disorder0.52

Genetic · overall 0.32

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

multiple sclerosis0.98

Clinical · overall 0.60

relapsing-remitting multiple sclerosis0.83

Clinical · overall 0.50

primary progressive multiple sclerosis0.61

Clinical · overall 0.37

kidney transplant0.57

Clinical · overall 0.34

chronic inflammatory demyelinating polyradiculoneuropathy0.43

Clinical · overall 0.26

Show all associations
multiple sclerosis0.60
hearing loss, autosomal recessive0.57
deafness0.53
relapsing-remitting multiple sclerosis0.50
Non-syndromic genetic deafness0.39
nonsyndromic genetic hearing loss0.37
primary progressive multiple sclerosis0.37
kidney transplant0.34
hypertensive disorder0.32
chronic inflammatory demyelinating polyradiculoneuropathy0.26

Open Targets ranks 1,369 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 5 total

FINGOLIMOD HYDROCHLORIDEApproval

multiple sclerosis · relapsing-remitting multiple sclerosis · kidney transplant

AMISELIMOD HYDROCHLORIDEPhase 2

Crohn disease · multiple sclerosis · psoriasis

FINGOLIMOD LAURYL SULFATEApproval

multiple sclerosis

AMISELIMODPhase 2

ulcerative colitis · multiple sclerosis · systemic lupus erythematosus

FINGOLIMODApproval

primary progressive multiple sclerosis · multiple sclerosis · relapsing-remitting multiple sclerosis

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Clinical trials

2

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

COMPLETED · via Fingolimod Hydrochloride · NCT03943498

COMPLETED · via Fingolimod Hydrochloride · NCT03941743

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

deafnessWell supported
0.79
agreement 0.670.91
Genetic71%Animal model28%Literature1%Genetic literaturedup

Open Targets aggregate 0.53 · 3 independent evidence families · 1 not counted as duplicate

hearing loss, autosomal recessiveWell supported
0.77
agreement 0.650.89
Genetic73%Animal model27%Literature0%Genetic literaturedup

Open Targets aggregate 0.57 · 3 independent evidence families · 1 not counted as duplicate

multiple sclerosisModerately supported
0.74
agreement 0.590.90
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

relapsing-remitting multiple sclerosisModerately supported
0.62
agreement 0.460.79
Clinical100%

Open Targets aggregate 0.50 · 1 independent evidence family

Non-syndromic genetic deafnessModerately supported
0.59
agreement 0.460.73
Genetic literature71%Animal model30%

Open Targets aggregate 0.39 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

3

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2023-09-05
    Glial Sphingosine-Mediated Epigenetic Regulation Stabilizes Synaptic Function in <i>Drosophila</i> Models of Alzheimer's Disease.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023 · 8 citations · Europe PMC · via Fingolimod Hydrochloride

  2. Regulatory approval2020-06-25

    Approval: Fingolimod Accord (EMA)

    ema · regulatory · ema · via Fingolimod Hydrochloride

  3. Regulatory approval2011-03-17

    Approval: Gilenya (EMA)

    ema · regulatory · ema · via Fingolimod Hydrochloride

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.