GPI ethanolamine phosphate transferase 3 (PIGO)

GPI ethanolamine phosphate transferase 3, commonly known as PIGO, is a critical enzyme involved in the biosynthesis of glycosylphosphatidylinositol (GPI) anchors, which attach numerous proteins to the eukaryotic cell membrane (UniProt PIGO, 2024). Specifically, PIGO catalyzes the transfer of ethanolamine phosphate to the third mannose of the GPI precursor, a step essential for the subsequent attachment of the protein to the anchor (PubMed: 10873116). Mutations in the PIGO gene are primarily associated with Hyperphosphatasia with Mental Retardation Syndrome 2 (HPMRS2), a rare autosomal recessive disorder characterized by intellectual disability, seizures, and elevated serum alkaline phosphatase (NIH: GARD, 2023). While PIGO is not currently a target for conventional small-molecule inhibitors, it is a subject of intense study in the context of rare disease diagnostics and potential gene replacement therapies. Understanding its function is vital for managing patients with GPI-anchor deficiencies, where the loss of cell-surface proteins leads to significant neurological and developmental impairments (PubMed: 22747753).

Other names

Phosphatidylinositol glycan anchor biosynthesis class OPIG-OGPI ethanolamine phosphate transferase IIIHPMRS2

There are currently no approved drugs or clinical-stage small molecules that directly target PIGO for therapeutic modulation; however, research focuses on gene therapy or substrate replacement strategies for deficiency syndromes.