Since the identification of the relationship between gne mutations and HIBM [13] , more than 60 mutations have been found to be associated with HIBM [24] . Among these mutations, 25 missense mutations at 23 unique sites are located in the kinase domain of the GNE protein. These 23 mutation sites can be classified into 4 different groups based on their solvent accessibility, and their locations ( Table 1 ).