SPNS2 Gene - Sphingolipid Transporter 2 | Function, Mutations & Diseases

SPNS2 encodes a transmembrane protein belonging to the major facilitator superfamily (MFS). It functions as a transporter of sphingosine-1-phosphate (S1P) across the plasma membrane, facilitating S1P export from cells. This export is critical for S1P receptor signaling, which regulates lymphocyte egress from lymphoid organs, vascular development, and auditory function. Mutations in SPNS2 cause autosomal recessive primary lymphedema with or without sensorineural hearing loss.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Sphingosine-1-phosphate (S1P) signaling pathway

• Lymphocyte egress from lymphoid organs

• Lymphatic vessel development

SPNS2 is a 549-amino acid multi-pass transmembrane protein with 12 predicted transmembrane helices. It belongs to the MFS family and specifically exports sphingosine-1-phosphate (S1P) from cells. S1P export by SPNS2 is essential for maintaining S1P gradients that guide lymphocyte trafficking and lymphatic endothelial cell migration. The protein is expressed in endothelial cells, lymphocytes, and inner ear tissues. Loss-of-function mutations cause primary lymphedema and sensorineural hearing loss.