Phosphatidylinositol glycan anchor biosynthesis class O (PIGO) (PIGO)

Phosphatidylinositol glycan anchor biosynthesis class O (PIGO) is an essential enzyme located in the endoplasmic reticulum that participates in the late stages of glycosylphosphatidylinositol (GPI) anchor biosynthesis (UniProt Q8TEQ8). It functions specifically as an ethanolamine phosphate transferase, catalyzing the transfer of ethanolamine phosphate to the third mannose residue of the GPI precursor (PubMed: 23354437). This modification is a prerequisite for the attachment of the GPI anchor to the carboxy-terminus of various proteins, which allows them to be tethered to the external leaflet of the plasma membrane (OMIM: 614749). Deficient PIGO function, typically caused by autosomal recessive mutations, leads to Hyperphosphatasia with Mental Retardation Syndrome 2 (HPMRS2), also known as Mabry syndrome (PubMed: 23354437). This condition is characterized by severely elevated serum alkaline phosphatase, intellectual disability, and often refractory seizures (OMIM: 614749). Because hundreds of cell surface proteins rely on GPI anchors for proper localization and function, PIGO deficiency results in systemic developmental and neurological impairment (UniProt Q8TEQ8). While there are currently no direct pharmacological activators of PIGO, management often involves symptomatic treatment of seizures with pyridoxine, and research into gene therapy and chemical chaperones is ongoing (PubMed: 30103161).

Other names

GPI ethanolamine phosphate transferase 3Phosphatidylinositol-glycan biosynthesis class O proteinHPMRS2PIGO

There are currently no approved drugs that directly bind to or activate PIGO; however, pyridoxine is used to manage seizures associated with PIGO deficiency by supporting GABAergic neurotransmission (PubMed: 23354437).