S1PR2

sphingosine-1-phosphate receptor 2, the group of Sphingosine 1-phosphate receptors

Basic information

Region (hg38): 19:10221433-10231331

Previous symbols: [ "EDG5", "DFNB68" ]

Links

ENSG00000267534 ∙ NCBI:9294 ∙ OMIM:605111 ∙ HGNC:3169 ∙ Uniprot:O95136 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 68 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 68 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Strong), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 68	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	16703383; 26805784

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the S1PR2 gene.

• not_provided (100 variants)
• Inborn_genetic_diseases (48 variants)
• not_specified (16 variants)
• S1PR2-related_disorder (7 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_68 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the S1PR2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004230.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	45	6	53
missense	2		69	10	1	82
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	0	71	55	7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
S1PR2	protein_coding	protein_coding	ENST00000590320	1	7429

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125736	0	10	125746	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.53	173	240	0.722	0.0000173	2217
Missense in Polyphen		48	81.192	0.59119		852
Synonymous	0.920	107	120	0.893	0.00000958	815
Loss of Function	1.49	4	8.76	0.457	4.65e-7	89

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

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. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis.
• Disease: DISEASE: Deafness, autosomal recessive, 68 (DFNB68) [MIM:610419]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:26805784}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Small Ligand GPCRs;Signal Transduction of S1P Receptor;Signaling by GPCR;Signal Transduction;Lysosphingolipid and LPA receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (i) signalling events;GPCR downstream signalling;Sphingosine 1-phosphate (S1P) pathway;S1P2 pathway (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• loftool: 0.137
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.155

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: s1pr2
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: activation of MAPK activity;sphingosine-1-phosphate receptor signaling pathway;G protein-coupled receptor signaling pathway;positive regulation of cell population proliferation;positive regulation of peptidyl-threonine phosphorylation;actin cytoskeleton reorganization;filopodium assembly;negative regulation of excitatory postsynaptic potential;positive regulation of establishment of endothelial barrier
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: G protein-coupled receptor binding;G protein-coupled receptor activity;integrin binding;protein binding;lipid binding;sphingosine-1-phosphate receptor activity