Molecular basis of inherited diseases: a structural perspective

Mutations in human genes can change the sequence and structure of a protein, impair its function, and could lead to disease. The increasing number of human protein structures provides an opportunity to explore further the molecular basis of many diseases. By studying inherited disease genes and analysing three-dimensional information, we can often explain why different phenotypes originate from mutations in the same gene. Although interpreting the effects of mutations in a protein structure can be difficult, it can provide more detailed information about the environment and role of a mutated residue than the protein sequence alone. Nevertheless, protein sequence information and evolutionary sequence conservation still remain powerful indicators of which mutations will impair the function of a gene product.