Molecular characteristics

GPAA1 is composed of an N-terminal transmembrane domain, a luminal region, and a hydrophobic region containing six transmembrane domains in the C terminus. Bi-allelic loss-of-function mutations in 17 patients have been reported. GPAA1 encodes a protein of the GPI-lipid-anchor transamidase complex involved in the attachment of the GPI anchor to the C- terminus of precursor proteins in the endoplasmic reticulum. Functional studies on individuals with GPAA1 mutations show a decrease in GPI-anchored proteins at the cell surface demonstrating a defect in the biosynthesis of GPI-anchored proteins (GPI-Aps). Approximately one in every 200 mammalian proteins is a GPI-anchored protein (GPI-Aps). These proteins are important for neurological development and function, embryogenesis, immune response, and signal transduction.