Variants affecting surface residues

Change of surface residues on a protein may affect its association with other proteins, though in practice changes in these regions have a less significant functional effect than changes in the core of the protein⁹.  Should a protein be involved in protein-protein, or protein-nucleic acid interactions, any variation of amino acids on the binding surface could lead to a loss of function.  

An example of this is Human DJ-1, which in rare forms of Parkinson’s disease, contains single mutations that destabilise the homodimeric interface, leading to disruption of function (Figure 9)¹⁰.