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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SPNS2
SPNS lysolipid transporter 2, sphingosine-1-phosphate
Chromosome 17 Β· 17p13.2
NCBI Gene: 124976Ensembl: ENSG00000183018.10HGNC: HGNC:26992UniProt: Q8IVW8
27PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
lipid transportsphingolipid intramembrane carrier activitysphingosine-1-phosphate receptor signaling pathwaysensory perception of soundhearing loss, autosomal recessivegenetic disordersensorineural hearing lossSensorineural hearing impairment
✦AI Summary

SPNS2 encodes a lipid transporter that specifically mediates export of sphingosine-1-phosphate (S1P) from cells, playing crucial roles in immune function and hearing 1. The protein functions through facilitated diffusion, distinct from other MFS lipid transporters, and undergoes conformational changes between inward-facing and outward-facing states to transport S1P across cell membranes 1. SPNS2 is essential for establishing S1P concentration gradients between high circulating levels and low tissue concentrations, which control lymphocyte trafficking and egress from lymphoid organs 2. The transporter is required for T-cell egress from lymph nodes during immune responses and immature B-cell egress from bone marrow 2. Beyond immune function, SPNS2 is critical for auditory function, as S1P release in the inner ear maintains the endocochlear potential necessary for hearing 3. Pathogenic mutations in SPNS2 cause autosomal recessive deafness (DFNB115) by ablating the protein's S1P export activity 3. The transporter also exports FTY720-P (fingolimod), making it central to the pharmacokinetics of this multiple sclerosis therapeutic 3. SPNS2 represents a potential therapeutic target for autoimmune diseases, cancer, and inflammatory conditions, with several inhibitors under development 45.

Sources cited
1
SPNS2 transports S1P via facilitated diffusion and undergoes conformational changes between inward- and outward-facing states
PMID: 37224812
2
SPNS2 establishes S1P gradients controlling lymphocyte trafficking and is required for T-cell and B-cell egress
PMID: 30655317
3
SPNS2 is critical for auditory function and pathogenic mutations cause hearing loss; transports FTY720-P
PMID: 39820269
4
SPNS2 is a potential therapeutic target for autoimmune diseases and inflammatory conditions
PMID: 27318702
5
SPNS2 inhibitors are under development as potential therapeutics
PMID: 37832799
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.48Moderate
genetic disorderOpen Targets
0.30Weak
sensorineural hearing lossOpen Targets
0.29Weak
Sensorineural hearing impairmentOpen Targets
0.29Weak
Hearing impairmentOpen Targets
0.12Weak
epilepsy, hearing loss, and intellectual disability syndromeOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.07Suggestive
immunodeficiency 18Open Targets
0.07Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.07Suggestive
isolated agammaglobulinemiaOpen Targets
0.07Suggestive
X-Linked Combined Immunodeficiency DiseasesOpen Targets
0.07Suggestive
common variable immunodeficiencyOpen Targets
0.07Suggestive
Alymphoid cystic thymic dysgenesisOpen Targets
0.07Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.07Suggestive
immunodeficiency 15aOpen Targets
0.07Suggestive
immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopeniasOpen Targets
0.06Suggestive
Deafness, autosomal recessive, 115UniProt
Pathogenic Variants2
NM_001124758.2(SPNS2):c.c.1066_1067delinsT (p.Pro356Cysfs)Likely pathogenic
Inborn genetic diseases|Hearing loss, autosomal recessive 115
β˜…β˜†β˜†β˜†2017β†’ Residue 356
NM_001124758.3(SPNS2):c.906G>A (p.Trp302Ter)Likely pathogenic
Sensorineural hearing loss disorder
β˜†β˜†β˜†β˜†β†’ Residue 302
View on ClinVar β†—
Related Genes
SPHK1Protein interaction83%S1PR2Protein interaction83%SPHK2Protein interaction83%MFSD2BProtein interaction70%PCTPShared pathway25%GRXCR2Shared pathway20%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
53%
Heart
21%
Liver
15%
Brain
14%
Ovary
4%
Gene Interaction Network
Click a node to explore
SPNS2SPHK1S1PR2SPHK2MFSD2BPCTPGRXCR2
PROTEIN STRUCTURE
Preparing viewer…
PDB8RL8 Β· 2.79 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.96LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.73 [0.56–0.96]
RankingsWhere SPNS2 stands among ~20K protein-coding genes
  • #12,683of 20,598
    Most Researched27
  • #4,527of 5,498
    Most Pathogenic Variants2
  • #9,023of 17,882
    Most Constrained (LOEUF)0.96
Genes detectedSPNS2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Structural and functional insights into Spns2-mediated transport of sphingosine-1-phosphate.
PMID: 37224812
Cell Β· 2023
1.00
2
Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.
PMID: 27318702
Drugs Β· 2016
0.90
3
Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney.
PMID: 38200266
Cell Mol Life Sci Β· 2024
0.80
4
Biological function of SPNS2: From zebrafish to human.
PMID: 30196234
Mol Immunol Β· 2018
0.70
5
Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.
PMID: 39820269
Nat Commun Β· 2025
0.60