Identification of EFL1 mutations in 3 individuals with SDS. Family pedigrees and direct Sanger sequencing of the EFL1 gene in individuals 1 (P1) (A), 2 (P2) (B), and 3 (P3) (C). Arrows indicate the position of the mutations. (D) Multiple sequence alignment of EFL1 proteins from representative species. Identical amino acids are shown in red with white characters, similar amino acids are in red character, and a blue frame represents similarity across groups. (E) Schematic of the domain architecture of human EFL1 showing the position of disease-associated mutations. Domains I to V are indicated; id, insertion domain (residues 424-502) that distinguishes EFL1 from other translational GTPases. (F) Mapping of SDS-associated mutations onto human EFL1 (Protein Data Bank accession number 5anc⁴ ), shown in ribbon representation. Domains are colored deep salmon (I), light orange (id, II), cyan (III), and light blue (IV). Residue K976 corresponds to K983 mutated in the N-ethyl-N-nitrosourea mutant mouse model (see below). WT, wild-type.