S1PR2

Chr 19AR

sphingosine-1-phosphate receptor 2

Also known as: AGR16, DFNB68, EDG-5, EDG5, Gpcr13, H218, LPB2, S1P2

NCBI Gene: 9294 ENSG00000267534 UniProt: O95136 OMIM: 605111

This gene encodes a member of the G protein-coupled receptors, as well as the EDG family of proteins. The encoded protein is a receptor for sphingosine 1-phosphate, which participates in cell proliferation, survival, and transcriptional activation. Defects in this gene have been associated with congenital profound deafness. [provided by RefSeq, Mar 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.041 OMIM phenotype

Clinical Summary— S1PR2

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARStrong

Strong evidence — appropriate for clinical testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 69 VUS of 144 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.018

Z-score 1.49

OE 0.46 (0.22–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.53Z-score

OE missense 0.72 (0.64–0.82)

173 obs / 239.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.22–1.04)

0≤0.351.4

Missense OE?0.72 (0.64–0.82)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 4 / 8.8Missense obs/exp: 173 / 239.5Syn Z: 0.92

This gene — mechanism propensity

0.73top 25%

GOF

0.85top 5%

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

144 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS69

Likely Benign53

Benign11

Conflicting6

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	0	68	0	1	69
Likely Benign	0	5	3	45	53
Benign	0	1	3	7	11
Conflicting	—				6
Total	0	76	6	53	141

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap S1PR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →