Developing a new method to predict the effect of the missense mutations on the protein function and phenotypes

Abstract

In a study published in August of 2017 in the journal Scientific Reports, Hijikata and his team investigated the functional effects of missense mutations on protein structure. ‘Mutations are either considered dominant or recessive, and of the dominant mutations there are three main types,’ outlines Hijikata. ‘Firstly, haploinsufficiency, where one copy of a gene is inactivated or deleted and the remaining copy is not adequate to produce the needed gene product or preserve the normal function. Secondly, dominant-negative, where there is an altered gene that has lost a certain part of its function. Then finally, gain-of-function, where the mutation causes a new function of the gene and produces a new phenotype.’ In the study, Hijikata found a clear relationship between the type of disease-causing missense mutation and the protein macromolecular structure. This discovery implies that it is possible to predict the functional and phenotypic outcomes of a given missense mutation just by looking at the protein’s structure.