S1PR4

protein-coding

sphingosine-1-phosphate receptor 4, the group of Sphingosine 1-phosphate receptors

Gene summary

This gene is a member of the endothelial differentiation, G-protein-coupled (EDG)) receptor gene family. EDG receptors bind lysophospholipids or lysosphingolipids as ligands, and are involved in cell signalling in many different cell types. This EDG receptor gene is intronless and is specifically expressed in the lymphoid tissue. [provided by RefSeq, Jul 2008]

Previous symbols:

EDG6

MANE transcript

NM_003775.4

Inheritance

—

ClinVar variants

U:96B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr19:3,172,346-3,180,332

External References & Databases

Ensembl (ENSG00000125910)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to S1PR4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003775.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	1 clinvar	6
missense			96 clinvar	3 clinvar		99
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	96	8	1	105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003775.4	RefSeq	NP_003766.1	1	MANE Select
ENST00000246115.5	Ensembl	ENSP00000246115.3	1	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
s1pr4	Danio rerio	Structure: neutrophil Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

s1pr4

Danio rerio

Structure: neutrophil

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

FoxO signaling pathway - Homo sapiens (human)
Sphingolipid signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Small Ligand GPCRs
Signaling by GPCR

Biological Process

sphingosine-1-phosphate receptor signaling pathway
immune response
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway
activation of phospholipase C activity

Molecular Function

G protein-coupled receptor activity
lipid binding
sphingosine-1-phosphate receptor activity

Cellular Component

mitochondrion
plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246115
Coding exons: 1
Length: 7986
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0789	262	266	0.986	0.0000201	2385
Missense (PolyPhen)		72	89.253	0.8067		971
Synonymous	-1.77	152	127	1.20	0.00000924	909
Loss of Function	1.01	5	8.09	0.618	4.29e-7	77

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. May be involved in cell migration processes that are specific for lymphocytes. {ECO:0000269|PubMed:10679247, ECO:0000269|PubMed:10753843}.;

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.0607
RVIS EVS: -0.53
RVIS percentile EVS: 20.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.938

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium