RAS mutations most commonly occur at codons 12, 13 and 61, but melanoma is almost exclusively associated with NRAS codon 61 mutations. Burd et al. sought to understand this site specificity, and they found that mice expressing NRAS-Q61R developed melanoma, whereas mice expressing NRAS-G12D did not. There was limited difference in the ability of NRAS-Q61R and NRAS-G12D to induce downstream signalling, but NRAS-Q61R had enhanced nucleotide binding and decreased GTPase activity, indicating that it is more active than NRAS-G12D.