S1PR1

protein-coding

sphingosine-1-phosphate receptor 1, the group of CD molecules|Sphingosine 1-phosphate receptors

Gene summary

The protein encoded by this gene is structurally similar to G protein-coupled receptors and is highly expressed in endothelial cells. It binds the ligand sphingosine-1-phosphate with high affinity and high specificity, and suggested to be involved in the processes that regulate the differentiation of endothelial cells. Activation of this receptor induces cell-cell adhesion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

Previous symbols:

EDG1

MANE transcript

NM_001400.5

Inheritance

—

ClinVar variants

U:25B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr1:101,236,865-101,243,713

External References & Databases

Ensembl (ENSG00000170989)

Transcript & Mutation Effects

hg38 • Region Span ~6.8 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 S1PR1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001400.5. 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			1 clinvar		1 clinvar	2
missense			24 clinvar		1 clinvar	25
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	25	0	2	27

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001400.5	RefSeq	NP_001391.2	1	MANE Select
ENST00000305352.7	Ensembl	ENSP00000305416.6	1	MANE Select
NM_001320730.2	RefSeq	NP_001307659.1	1	Standard
ENST00000475289.2	Ensembl	ENSP00000498038.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
s1pr1	Danio rerio	Structure: nucleate erythrocyte Quality: increased accumulation abnormal

Gene / Model

Organism

Observed Phenotype

s1pr1

Danio rerio

Structure: nucleate erythrocyte

Quality: increased accumulation

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)
GPCRs, Other
Small Ligand GPCRs

Biological Process

angiogenesis
blood vessel maturation
cardiac muscle tissue growth involved in heart morphogenesis
sphingosine-1-phosphate receptor signaling pathway
chemotaxis

Molecular Function

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

Cellular Component

nucleoplasm
endosome
plasma membrane
external side of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305352
Coding exons: 1
Length: 4631
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125685
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.61	120	232	0.518	0.0000157	2487
Missense (PolyPhen)		19	78.035	0.24348		883
Synonymous	-0.177	106	104	1.02	0.00000737	818
Loss of Function	2.42	1	8.68	0.115	5.45e-7	107

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00020	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3- phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury. {ECO:0000250, ECO:0000269|PubMed:10982820, ECO:0000269|PubMed:11230698, ECO:0000269|PubMed:11583630, ECO:0000269|PubMed:11604399, ECO:0000269|PubMed:19286607, ECO:0000269|PubMed:22344443, ECO:0000269|PubMed:8626678, ECO:0000269|PubMed:9488656}.;

Recessive Scores

pRec: 0.184

Intolerance Scores

LoFtool: 0.0757
RVIS EVS: 0.06
RVIS percentile EVS: 58.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.773

Gene Damage Prediction

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