Evolutionary history of calcium-sensing receptors unveils hyper/hypocalcemia-causing mutations
Fig 7
LoF and GoF Mutation Predictions. (A)Visualizing the results of our XGBoost model.
The heatmap displays the XGBoost model’s predictions for each of the 20 amino acids at every position except disordered regions (892–1078) within the human CaSR. Above the heatmap, the domains of the CaSR are shown. Within these domains, circles represent all known LoF and GoF mutations documented in the literature. Circles denoting GoF mutations are colored purple, while those representing LoF mutations are colored blue. Below the heatmap bar graphs show the number of GoF, LoF and neutral predictions among the 19 possible substitutions. (B) Mutations on the human CaSR structure. LoF- and GoF-associated mutations are shown on the cryo-EM structure of human CaSR bound with Ca2+ and L-Trp (PDB:7DTV) as blue and red spheres, respectively. (C) Increased residue-residue contacts are shown on the cryo-EM structure of human CaSR bound with Ca2+ and L-Trp (PDB:7DTV) on the left. Interdomain and intrasubunit interactions are shown as red and blue lines, respectively on the right. LoF- and GoF-associated mutations among the interacted residues are shown as blue and purple spheres, respectively. Switch residues are shown as yellow spheres.