Figure 7.

Glucagon receptor in vitro mutations in the literature.A, in vitro mutations tested on binding obtained from literature annotations (n = 203, left) and tested in the present study (n = 19, right). B, in vitro mutations tested in cAMP accumulation or production experiments annotated from published studies (n = 59, left) and tested in the present study (n = 38, right). Of note, the vast majority of previously performed mutations are performed to conduct receptor structural investigations and to probe ligand interactions mostly employing Alanine or Cysteine mutations. The fraction of drastic effects is less frequently observed in human genetic variations indicating purifying selection on the most extreme phenotypes. Effects have been grouped into WT-like <5-fold difference (gray), ≥5-fold but <10-fold (yellow), ≥10-fold difference (orange), and no activity (red).