Structural and functional changes caused by pathogenic variants in diabetes causing genes HNF1A and HNF1B

Abstract

The HNF-1α and HNF-1β proteins are polymorphic in character, which contribute to the broader clinical variability that is linked with type 2 diabetes. Therefore, genotyping must be undertaken to gather further information about the HNF-1α and HNF-1β to have a better understanding of effective regulation of aberrant blood glucose levels that are produced because of HNF-1α and HNF-1β mutations. These mutations give rise to various forms of diabetes such as hyperglycemia, which is a major form of diabetes. This hyperglycemia is caused by a defect in the HNF-1α protein. This study utilizes homology modeling and molecular dynamics to evaluate the structure-function changes that are associated with HNF-1α and HNF-1β mutations. Using sequence comparison, structure prediction and molecular dynamics, an investigation of twelve missense and pathogenic mutations was carried out. Sequence comparisons revealed that most of the phenotypes were located within the fully conserved residues of HNF-1α and HNF-1β. On the other hand, some of the residues were found to be located within the semi-conserved residues. In addition, the mean of the solvent-accessible surface area (ASA) of models was lower than that for mutants. RESIs MD These findings give a deeper insight into the structure-function features of HNF-1α and HNF-1β mutations. They may also be beneficial in predicting the severity of type 2 diabetes based on future genotyping.