We pooled data of all AML patients to identify not only predominant mutation types in proteins such as FLT3 (in-frame insertion), NPM1 (frameshift insertion), CEBPA (in-frame deletion), TET2 (nonsense, in-frame deletion) and ASXL1 (frameshift, nonsense), which have been used as genomic classifiers (42), but also the enrichment of mutations in a single amino acid position or those which localize in close vicinity in the 3D protein structure, defined as ‘mutation hotspots’. The gene discussed is NPM1; the disease is acute myeloid leukemia.