SPNS2

Chr 17AR

SPNS lysolipid transporter 2, sphingosine-1-phosphate

Also known as: DFNB115, SLC62A2, SLC63A2

NCBI Gene: 124976ENSG00000183018UniProt: Q8IVW8

The protein encoded by this gene is a transporter of sphingosine 1-phosphate, a secreted lipid that is important in cardiovascular, immunological, and neural development. Defects in this gene are a cause of early onset progressive hearing loss. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 115MIM #618457
AR
212
ClinVar variants
25
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SPNS2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 124 VUS of 212 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.000
Z-score 2.31
OE 0.49 (0.32–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.07Z-score
OE missense 1.01 (0.92–1.11)
315 obs / 311.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.49 (0.32–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.45
0≤1.21.6
LoF obs/exp: 12 / 24.3Missense obs/exp: 315 / 311.6Syn Z: -4.15

ClinVar Variant Classifications

212 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic3
VUS124
Likely Benign27
Benign36
22
Pathogenic
3
Likely Pathogenic
124
VUS
27
Likely Benign
36
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
1
0
2
0
3
VUS
0
100
24
0
124
Likely Benign
0
6
6
15
27
Benign
0
2
31
3
36
Total11088518212

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

View in ClinVar →

Protein Context — Lollipop Plot

SPNS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Deafness, autosomal recessive 115

MIM #618457

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.
Li HZ et al.·Nat Commun
2025
Spinster homolog 2 (SPNS2) deficiency drives endothelial cell senescence and vascular aging via promoting pyruvate metabolism mediated mitochondrial dysfunction.
Tang H et al.·Cell Commun Signal
2024
Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors.
Fritzemeier R et al.·J Med Chem
2022
Lack of SPNS1 results in accumulation of lysolipids and lysosomal storage disease in mouse models.
Ha HT et al.·JCI Insight
2024Functional
Prognostic Significance of Cytoplasmic SPNS2 Expression in Patients with Oral Squamous Cell Carcinoma.
Lu JW et al.·Medicina (Kaunas)
2021Cohort
Intra-tumor heterogeneity-resistant gene signature predicts prognosis and immune infiltration in breast cancer.
Shen H et al.·Front Immunol
2025
Long non-coding RNA HOXA-AS3 facilitates the malignancy in colorectal cancer by miR-4319/SPNS2 axis.
Jiang Y et al.·J Physiol Biochem
2021
Sphingolipid metabolism patterns reveal distinct prognostic and immune landscapes in head and neck squamous cell carcinoma.
Yue B et al.·Pathol Res Pract
2025
A Genome-Wide Association Study of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis.
Gaastra B et al.·Transl Stroke Res
2023Meta-analysis
Several Common Genetic Variations Associate With Functional or Anatomic Effects of Anti-VEGF Treatment in Conditions With Macular Edema.
Klaassen I et al.·Invest Ophthalmol Vis Sci
2025Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools