Fig. 2

Map of glucokinase variant abundance. A Heatmap showing the abundance scores of 8822 missense and nonsense (*) glucokinase variants, as well as the median score at each position (MED). The wild-type amino acid at each position is shown in yellow. Missing variants are shown in gray. Above the heatmap, the regions forming the hinge region (gray) and the large (light blue) and small (light orange) domains are represented as a bar. In addition, the relative solvent accessible surface area (rASA) of each residue in the closed and super-open conformations is shown. B Abundance score distributions of glucokinase missense, synonymous, and nonsense variants. Dashed lines indicate the scores of three variants tested in low-throughput to be unstable (E300K) or wild-type-like (D205H and D217N). C The closed active state of glucokinase colored by median abundance scores. The coloring scheme is the same as in panel A. Glucose is shown in orange. PDB: 1V4S