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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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S1PR4
sphingosine-1-phosphate receptor 4
Chromosome 19 · 19p13.3
NCBI Gene: 8698Ensembl: ENSG00000125910.6HGNC: HGNC:3170UniProt: O95977
36PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
sphingosine-1-phosphate receptor signaling pathwayprotein bindingmitochondrionG protein-coupled receptor signaling pathwaymultiple sclerosisrelapsing-remitting multiple sclerosisulcerative colitisprimary progressive multiple sclerosis
✦AI Summary

S1PR4 (sphingosine-1-phosphate receptor 4) is a G protein-coupled receptor that plays crucial roles in immune cell regulation and inflammatory responses. As a receptor for sphingosine-1-phosphate (S1P), S1PR4 modulates immune cell trafficking and activation across multiple cell types 1. The receptor is primarily expressed in immune cells, particularly CX3CR1+ CD8+ effector T cells, where S1P/S1PR4 signaling promotes cell migration and facilitates differentiation into tissue-resident memory T cells 2. In myeloid cells, S1PR4 attenuates pro-inflammatory cytokine production in macrophages and regulates neutrophil activation, demonstrating anti-inflammatory effects 1. S1PR4 also influences neutrophil trafficking and circulating counts, as evidenced by genetic variants affecting neutrophil levels 3. Therapeutically, S1PR4 represents a promising target for inflammatory diseases. Etrasimod, an S1PR1/4/5 modulator, has shown efficacy in ulcerative colitis by inhibiting lymphocyte trafficking from lymph nodes 4. In biliary atresia models, S1PR4 inhibition reduced liver inflammation and fibrosis 2. The receptor's expression has also been identified as a potential biomarker for coronary artery disease 5, highlighting its broader clinical relevance beyond immune disorders.

Sources cited
1
S1PR4 is a G protein-coupled receptor that attenuates pro-inflammatory cytokine production in macrophages and regulates neutrophil activation
PMID: 40342995
2
S1PR4 is primarily expressed in CX3CR1+ CD8+ effector T cells and promotes cell migration and differentiation into tissue-resident memory T cells
PMID: 40915360
3
Genetic variants in S1PR4 affect neutrophil trafficking and circulating neutrophil counts
PMID: 27399967
4
Etrasimod, an S1PR1/4/5 modulator, shows efficacy in ulcerative colitis by inhibiting lymphocyte trafficking
PMID: 36789612
5
S1PR4 expression serves as a potential biomarker for coronary artery disease
PMID: 31245869
Disease Associationsⓘ20
multiple sclerosisOpen Targets
0.59Moderate
relapsing-remitting multiple sclerosisOpen Targets
0.59Moderate
ulcerative colitisOpen Targets
0.55Moderate
primary progressive multiple sclerosisOpen Targets
0.40Moderate
kidney transplantOpen Targets
0.39Weak
COVID-19Open Targets
0.34Weak
severe acute respiratory syndromeOpen Targets
0.33Weak
hypothyroidismOpen Targets
0.33Weak
thyroid diseaseOpen Targets
0.33Weak
femur fractureOpen Targets
0.29Weak
Hashimoto's thyroiditisOpen Targets
0.29Weak
chronic inflammatory demyelinating polyradiculoneuropathyOpen Targets
0.26Weak
Crohn's diseaseOpen Targets
0.16Weak
strokeOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
inflammatory bowel diseaseOpen Targets
0.08Suggestive
asthmaOpen Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
psoriasisOpen Targets
0.08Suggestive
alopecia areataOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets7
AMISELIMODPhase II
Sphingosine 1-phosphate receptor modulator
ulcerative colitis
AMISELIMOD HYDROCHLORIDEPhase II
Sphingosine 1-phosphate receptor modulator
Crohn's disease
ETRASIMODApproved
Sphingosine 1-phosphate receptor Edg-1 agonist
ulcerative colitis
ETRASIMOD ARGININEApproved
Sphingosine 1-phosphate receptor Edg-8 modulator
ulcerative colitis
FINGOLIMODApproved
Sphingosine 1-phosphate receptor agonist
primary progressive multiple sclerosis
FINGOLIMOD HYDROCHLORIDEApproved
Sphingosine 1-phosphate receptor agonist
multiple sclerosis
FINGOLIMOD LAURYL SULFATEApproved
Sphingosine 1-phosphate receptor binding agent
multiple sclerosis
Related Genes
GPR6Shared pathway100%GPR12Shared pathway100%S1PR1Protein interaction95%GNA13Protein interaction92%SPHK2Protein interaction92%GNAI2Protein interaction91%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
49%
Liver
7%
Heart
1%
Ovary
1%
Brain
0%
Gene Interaction Network
Click a node to explore
S1PR4GPR6GPR12S1PR1GNA13SPHK2GNAI2
PROTEIN STRUCTURE
Preparing viewer…
PDB2DCO · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.89LoF Tolerant
pLIⓘ
0.16Tolerant
Observed/Expected LoF1.01 [0.27–1.89]
RankingsWhere S1PR4 stands among ~20K protein-coding genes
  • #10,856of 20,598
    Most Researched36
  • #325of 1,025
    FDA-Approved Drug Targets5
  • #17,235of 17,882
    Most Constrained (LOEUF)1.89
Genes detectedS1PR4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Etrasimod for the treatment of ulcerative colitis.
PMID: 36789612
Immunotherapy · 2023
1.00
2
Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases.
PMID: 35785704
Biomed Pharmacother · 2022
0.90
3
Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology.
PMID: 32278039
Pharmacol Res · 2020
0.80
4
S1PR4-dependent effects of Etrasimod on primary human myeloid immune cell activation.
PMID: 40342995
Front Pharmacol · 2025
0.70
5
Broad and diverse roles of sphingosine-1-phosphate/sphingosine-1-phosphate receptors in the prostate.
PMID: 39618500
iScience · 2024
0.60