Studies delineating the novel GBA1 D137N mutation. (A) Sanger traces showing heterozygous G > A changes from the parents and homozygous changes from the affected children. (B) Conservation of D137 among orthologs of GBA1. The amino acid segment 129-145 of human GBA1 is shown. Positions identical to human amino acids are highlighted in yellow. H.s. indicates Homo sapiens; M.m., Mus musculus; X.l., Xenopus laevis; D.r., Danio rerio; C.i., Ciona intestinalis; and C.e., C elegans. (C). Overlay of wild-type GBA (2V3E, white) and in silico folded D137N GBA (SWISS-MODEL algorithm, pink) and detailed view of D137N-induced loop change (D). Docking analysis of artificial substrate 4MUGlc on wild-type GBA1 (E) and D137N GBA1 (SWISS-MODEL, F), with distances depicted in Angstroms. Associated energies are depicted in supplemental Figure 3.