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Protein / target

Sphingosine 1-phosphate receptor 2

Encoded byS1PR2O95136Homo sapiensSwiss-Prot
UniProt: O95136Ensembl: ENSG00000267534HGNC: HGNC:3169NCBI Gene: 9294
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
2
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

G protein-coupled peptide receptor

Strongest disease association

Deafness

Via encoding gene S1PR2 · Genetic evidence · score 0.71

Therapeutic position

Established drug target

Small molecules

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 overview

Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P).

View complete UniProt function annotation

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.

Synaptic signallingGOCell proliferation & survivalGOLipid & lipoprotein metabolismUniProtG protein-coupled signallingGO
View supporting evidence

Synaptic signalling

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

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Lipid & lipoprotein metabolism

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

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
View underlying pathways (2)
G alpha (i) signalling events
Lysosphingolipid and LPA receptors

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.

Approved medicines with mapped indications

1 medicine · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Multiple Sclerosis1 medicine
Fingolimod Hydrochloride
Multiple Sclerosis, Relapsing-Remitting1 medicine
Fingolimod Hydrochloride

3 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Fingolimod Hydrochloride
ApprovedAgonist

Sphingosine 1-phosphate receptor agonist

Indicated for Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene S1PR2

Gene-level evidence surfaced through the gene S1PR2that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Deafness
0.79Well supported

Genetic evidence dominant · Open Targets 0.53

Hearing loss, autosomal recessive
0.77Well supported

Genetic evidence dominant · Open Targets 0.57

Multiple Sclerosis
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

Non-syndromic genetic deafness
0.59Moderately supported

Genetic literature evidence dominant · Open Targets 0.39

Hypertension
0.53Moderately supported

Genetic evidence dominant · Open Targets 0.32

View evidence synthesis (5)
DeafnessWell supported
0.79
agreement 0.67–0.91
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 0.65–0.89
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 0.59–0.90
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

Non-syndromic genetic deafnessModerately supported
0.59
agreement 0.46–0.73
Genetic literature71%Animal model30%

Open Targets aggregate 0.39 · 2 independent evidence families

HypertensionModerately supported
0.53
agreement 0.39–0.67
Genetic99%Literature1%

Open Targets aggregate 0.32 · 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 per-type scores above show the calculation.

Show all associations
Multiple Sclerosis0.60
Hearing loss, autosomal recessive0.57
Deafness0.53
Non-syndromic genetic deafness0.39
Nonsyndromic genetic hearing loss0.37
Hypertension0.32

Drug development

5 compounds recorded · 3 approved · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (5)
FINGOLIMOD HYDROCHLORIDEApproval
AMISELIMOD HYDROCHLORIDEPhase 2
FINGOLIMOD LAURYL SULFATEApproval
AMISELIMODPhase 2
FINGOLIMODApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
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

Raw Open Targets tractability assessment buckets, by modality.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Prevention of Paclitaxel-Associated Neuropathy With Fingolimod: a Pilot TrialPHASE1

COMPLETED · via Fingolimod Hydrochloride · NCT03941743

Treatment of Established Chemotherapy-Induced Neuropathy With Fingolimod: A Pilot TrialEARLY_PHASE1

COMPLETED · via Fingolimod Hydrochloride · NCT03943498

ClinicalTrials.gov via the drug-target graph.

What's happening now

3

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  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.