SphK12

SPHK12 is a nonstandard symbol that may be used in some databases or analyses to refer collectively to the sphingosine kinase gene family, specifically SPHK1 and SPHK2. It is not generally recognized as a single, independent gene. In humans, SPHK1 and SPHK2 encode two related lipid kinases that catalyze the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P).

SPHK1 and SPHK2 share enzymatic activity but differ in localization and regulation. SPHK1 is predominantly cytosolic and translocates to the plasma membrane upon activation, whereas SPHK2 localizes to the nucleus, mitochondria, and endoplasmic reticulum. Both enzymes use ATP as a phosphate donor and produce S1P, a bioactive lipid that signals through cell-surface S1P receptors (S1PR1-5) and various intracellular targets.

Physiological roles include regulation of cell growth, survival, migration, angiogenesis, and immune responses. Expression and activity are modulated by growth factors, cytokines, and cellular stress. Isoform diversity from alternative splicing exists for SPHK1 and SPHK2, and selective inhibitors have been developed for research and therapeutic purposes. The immunomodulatory drug fingolimod (FTY720) is phosphorylated by SPHKs to an active S1P receptor modulator.

Clinical significance: Dysregulation of SPHK1/2 has been linked to cancer, inflammatory diseases, and neurodegenerative disorders. Because of their central role in S1P signaling, SPHK1/2 are considered potential therapeutic targets, with inhibitors and modulators undergoing clinical and preclinical evaluation. When encountered, the SPHK12 designation should be interpreted as referring to the SPHK1/2 gene family rather than a distinct gene.