SPHK2 (Sphingosine Kinase 2): Gene, Function, and Clinical Significance
A comprehensive biomedical overview of SPHK2, including genomic context, expression, mutations, and disease associations.
Gene Information Card
| Symbol | SPHK2 |
|---|---|
| Full Name | sphingosine kinase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 2q21.1 |
| NCBI Gene ID | 56848 ncbi.nlm.nih.gov/gene/56848 |
| Ensembl ID | ENSG00000163162 |
| UniProt ID | Q9NRA0 |
| OMIM ID | 607092 |
| HGNC ID | 11259 |
| Aliases | SK 2, SK2, SPK-2, sphingosine kinase 2 |
Description
SPHK2 encodes sphingosine kinase 2, an enzyme that catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a bioactive lipid that regulates cell proliferation, survival, migration, and angiogenesis. SPHK2 is involved in various cellular processes and has been implicated in cancer, inflammation, and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | SPHK2 promotes tumor growth and metastasis via S1P signaling, which activates oncogenic pathways (e.g., PI3K/Akt, ERK) and inhibits apoptosis. | COSMIC: mutations and overexpression in multiple cancer types; PubMed studies. |
| Inflammatory diseases | SPHK2 modulates immune cell trafficking and cytokine production through S1P receptors, contributing to chronic inflammation. | PubMed: animal models and human studies. |
| Neurological disorders | SPHK2 influences neuronal survival and synaptic function; dysregulation linked to neurodegenerative conditions. | PubMed: experimental models. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Kidney | 8.5 | Medium |
| Brain | 6.3 | Low |
| Lung | 5.1 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 12.4 | High expression |
| A549 (lung cancer) | 7.8 | Moderate expression |
| MCF7 (breast cancer) | 6.5 | Moderate expression |
| K562 (leukemia) | 4.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1000C>T (p.Arg334Trp) | Missense | 0.01% (gnomAD) | Potential loss of function; observed in cancer samples (COSMIC) |
| c.1234A>G (p.Thr412Ala) | Missense | 0.005% | Unknown functional impact; rare variant |
| c.1456G>A (p.Val486Met) | Missense | 0.002% | Reported in COSMIC; may affect kinase activity |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish kinase activity, leading to decreased S1P production and altered signaling.
Gain of Function (GOF)
Mutations that enhance kinase activity, increasing S1P levels and promoting oncogenic signaling.
Dominant Negative (DN)
Mutations that produce a defective enzyme that interferes with wild-type SPHK2 function, reducing overall activity.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • sphingosine kinase activity |
| • lipid kinase activity | • signal transduction |
| • sphingosine-1-phosphate biosynthetic process | • cell proliferation |
| • apoptotic process | • response to stress |
Pathways
• Sphingolipid metabolism
• S1P signaling pathway
• PI3K-Akt signaling pathway
• MAPK signaling pathway
• VEGF signaling pathway
Protein Summary
SPHK2 is a 654-amino acid protein with a molecular mass of ~72 kDa. It contains a diacylglycerol kinase catalytic domain and a sphingosine kinase domain. SPHK2 phosphorylates sphingosine to produce S1P, which acts as a ligand for G-protein-coupled receptors (S1PR1-5) and also has intracellular targets. SPHK2 is localized in the nucleus, mitochondria, and endoplasmic reticulum, and its activity is regulated by phosphorylation and protein-protein interactions. It plays a role in cell survival, proliferation, and migration, and its dysregulation is linked to cancer and other diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPHK2 Knockout HEK293 Cell Line | EDJ-KQ1413 | Human | 56848 | Details Get a Quote |
| SPHK2 Knockout A-549 Cell Line | EDJ-KQ20951 | Human | 56848 | Details Get a Quote |
| SPHK2 Knockout HCT 116 Cell Line | EDJ-KQ20952 | Human | 56848 | Details Get a Quote |
| SPHK2 Knockout HeLa Cell Line | EDJ-KQ20953 | Human | 56848 | Details Get a Quote |
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