Phosphatidylinositol glycan class A protein (PIGA)

Phosphatidylinositol glycan class A protein (PIGA) is the catalytic subunit of the glycosylphosphatidylinositol N-acetylglucosaminyltransferase (GPI-GnT) complex, which catalyzes the initial step in the biosynthesis of GPI anchors: the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol, forming GlcNAc-PI[1][2][5][6]. GPI anchors are essential glycolipid modifications that tether many proteins, including complement regulatory proteins, to the cell membrane, mediating a range of functions such as cell adhesion, signal transduction, and protection from complement-mediated lysis[1][2][4]. Pathogenic somatic mutations in *PIGA* are responsible for paroxysmal nocturnal hemoglobinuria (PNH), wherein hematopoietic stem cells lacking functional PIGA produce blood cells deficient in GPI-anchored proteins, predisposing to hemolysis, thrombosis, and bone marrow failure syndromes[1][3][4][5][6]. Germline PIGA mutations underlie severe neurodevelopmental disorders with congenital anomalies, seizures, and hypotonia[5][6]. PIGA is an X-linked gene, making males and females functionally hemizygous at the cellular level[1][3]. Complete loss of PIGA function is incompatible with life[5]. GPI-anchor deficiency is typically detected by flow cytometry for cell surface proteins CD55 and CD59, which serve as relevant biomarkers in PNH[5][6]. Interventions for PIGA-driven diseases focus on blocking downstream complement activation rather than directly targeting PIGA[1][6].

Other names

Phosphatidylinositol N-acetylglucosaminyltransferase subunit APIG-AGPI3GlcNAc-PI synthesis proteinPhosphatidylinositol-glycan biosynthesis class A proteinparoxysmal nocturnal hemoglobinuria geneMultiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2)GPI anchor biosynthesis class A proteinphosphatidylinositol-glycan biosynthesis, class A proteinGLCNAC-PI synthesis proteinPNH1

Inhibition of downstream complement cascade (by eculizumab or ravulizumab) to prevent hemolysis in PNH patients with PIGA mutations