RIMS2 and melanoma: In contrast, compared with 90 mis-sense plus truncating mutations in PRKAA2 (0.16 per residue) there were just seven mis-sense mutations (0.013 per residue) in the PRKAA1 gene (encoding the AMPK-α1 isoform) reported in melanoma or non-melanoma skin cancer, and there were no mutations at all affecting the ‘hot-spots' identified in the AMPK-α2 gene, i.e. the activation loop (AL), AID or RIM2 region of the α-linker (Figure 1B).