ETNK1 Gene – Ethanolamine Kinase 1: Function, Mutations, and Disease Association

ETNK1 (ethanolamine kinase 1) encodes a cytosolic enzyme that catalyzes the first committed step in the Kennedy pathway of phosphatidylethanolamine (PE) synthesis, phosphorylating ethanolamine to phosphoethanolamine. The gene is located on chromosome 12p12.1 and is widely expressed, with highest levels in the liver, kidney, and testis. Recurrent somatic missense mutations (e.g., N244S, N244T) have been identified in patients with atypical chronic myeloid leukemia (aCML) and other myelodysplastic/myeloproliferative neoplasms (MDS/MPN), leading to increased enzymatic activity and altered phospholipid homeostasis. ETNK1 is considered a potential oncogene in myeloid malignancies.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Kennedy pathway (phosphatidylethanolamine biosynthesis)

• Glycerophospholipid metabolism

Ethanolamine kinase 1 (ETNK1) is a 45 kDa cytosolic enzyme that phosphorylates ethanolamine using ATP, producing phosphoethanolamine. This is the rate-limiting step in the Kennedy pathway for phosphatidylethanolamine (PE) synthesis, a major membrane phospholipid. The protein contains a conserved choline/ethanolamine kinase domain. Gain-of-function mutations at residue N244 (N244S/T) enhance catalytic activity, leading to increased phosphoethanolamine levels, which may promote cell proliferation and survival in myeloid neoplasms. ETNK1 is also implicated in lipid signaling and membrane biogenesis.