DGKE Gene: Diacylglycerol Kinase Epsilon - Function, Mutations, and Associated Diseases

The DGKE gene encodes diacylglycerol kinase epsilon (DGKε), an enzyme that phosphorylates diacylglycerol (DAG) to produce phosphatidic acid (PA). DGKε is a member of the type I diacylglycerol kinase family and is characterized by its substrate specificity for arachidonoyl-containing DAG species. It plays a critical role in the phosphoinositide cycle and intracellular signaling, particularly in endothelial cells and platelets. Loss-of-function mutations in DGKE cause an autosomal recessive form of atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Phosphatidylinositol phosphate metabolism (Reactome: R-HSA-1483257)

• Diacylglycerol kinase pathway (Reactome: R-HSA-426048)

• GPCR downstream signaling (Reactome: R-HSA-388396)

Diacylglycerol kinase epsilon (DGKε) is a 567-amino acid protein with a molecular weight of approximately 64 kDa. It contains a conserved catalytic domain and two cysteine-rich zinc finger-like domains (C1 domains) that mediate membrane association. DGKε is unique among DGK isoforms in its specificity for arachidonoyl-containing diacylglycerol (DAG) species. The enzyme converts DAG to phosphatidic acid (PA), thereby terminating DAG signaling and modulating protein kinase C (PKC) activation. DGKε is highly expressed in kidney, brain, and endothelial cells. Loss of DGKε function leads to accumulation of arachidonoyl-DAG, which activates PKC and other effectors, contributing to endothelial dysfunction and microvascular thrombosis characteristic of atypical hemolytic uremic syndrome (aHUS).