BAYAT eT Al
| INTRODUCTIONGlycosylphosphatidylinositol (GPI) is a glycolipid that is synthetized and transferred to proteins in the membrane of the endoplasmic reticulum. 1 Biogenesis of GPI-anchored proteins (GPI-APs) is a conserved posttranslational mechanism in eukaryotes and is important for attaching these proteins to the cell membrane and for protein sorting, trafficking, and dynamics. 1,2 GPI synthesis and GPI-AP modification are mediated by at least 31 genes, and pathogenic variants in 22 of these genes have been associated with human disease to date. 3 The X-linked phosphatidylinositol glycan class A protein gene (phosphatidylinositol glycan class A protein [PIGA]) is part of a heptameric enzyme complex catalyzing the transfer of N-acetylglucosamine (GlcNAc) to phosphatidylinositol as the first step in GPI anchor biosynthesis. [4][5][6] In contrast to other members of the GPI-GlcNAc transferase complex, PIGA is an integral membrane protein with only one transmembrane domain residing in the endoplasmic reticulum (ER). The large N-terminal cytoplasmic domain contains two Rossmann folds. 7 Pathogenic germline missense variants in PIGA are associated with multiple congenital anomalies-hypotonia-seizures syndrome 2 (OMIM 316818). [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The affected
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.