Fig. 4. Structural basis for disease-associated ALS and IGF1 mutations.

a Schematic representation of the ALS protein indicating the location of the 27 identified mutations from patients with ASCLD. b Mutated residues in patients with ASCLD (only point mutations) are presented as green spheres and labeled in the cartoon structure of human ALS. c Close-up views of four cases (T145K, L172F, S490W, and C540R) of ALS mutations and their neighboring residues. d Mutated IGF1 residues in human patients with growth impairment are indicated in a schematic representation (left) and presented as green spheres and labeled in a cartoon structure of human IGF1 (right). e Close-up views of three IGF1 mutants (Y60H, R36Q, and V44M) and their neighboring residues.