Evolutionary history of calcium-sensing receptors unveils hyper/hypocalcemia-causing mutations.

ABSTRACT: Despite advancements in understanding the structure and functions of the Calcium Sensing Receptor (CaSR), gaps persist in our knowledge of the specific functions of its residues. In this study, we used phylogeny-based techniques to identify functionally equivalent orthologs of CaSR, predict residue significance, and compute specificity-determining position (SDP) scores to understand its evolutionary basis. The analysis revealed exceptional conservation of the CaSR subfamily, emphasizing the critical role of residues with high SDP scores in receptor activation and pathogenicity. To further enhance the findings, gradient-boosting trees were applied to differentiate between gain- and loss-of-function mutations responsible for hypocalcemia and hypercalcemia. Lastly, we investigated the importa

SUBMITTER: Bircan A 

PROVIDER: S-EPMC11584096 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature