Based on their melanoma‐specificity (p‐value), effect size (scaled BF score), and gene function, we proceeded with functional in vitro studies of two genes encoding for proteins with a reported inhibitory effect on MAPK signaling activity, DUSP4 and PPP2R2A. DUSP4 was a significant fitness gene in 16 melanoma cell lines including one NRAS‐mutant, and PPP2R2A significantly affected fitness of 16 melanoma cell lines, including one NRAS‐mutant and one NF1‐mutant (Supplemental Figure 1, Figure 2). This evidence concerns the gene DUSP4 and melanoma.