Fig. 4

a Schematic diagram of the TRNT1 gene demonstrating the mutations reported to date. Mutations found in the milder adult phenotype are shaded in blue and those found in childhood-onset severe disease are shaded in pink. b The human TRNT1 protein is shown in ribbon representation. All missense mutations published to date are shown as space fill atoms, white for carbon, red for oxygen and blue for nitrogen. The mutant residue is shown at each position and labelled. c Stick representation of the environment surrounding the p.Arg190Ile mutation. Carbon atoms in white, oxygen in red and nitrogen in blue. Ile190 is shown in green throughout. Hydrogen bonds are shown as dotted lines. The extensive hydrogen bond network stabilising the wildtype Arg190 is completely lost following mutation to the hydrophobic Ile190. d Stick representation of the environment surrounding the p,Ile223Thr mutation. Carbon atoms in white, oxygen in red and nitrogen in blue. Wildtype Ile223 is shown in green throughout. Hydrogen bonds are shown as dotted lines. The protein is able to accommodate the Thr223 mutation in place of the buried, hydrophobic Ile223 through the hydrogen bond from the Thr223 sidechain