The Cancer Genome Atlas (TCGA) data16 was used to rank all recurrent missense mutations in RBPs by overall frequency (Fig. 1d), which recovered the top three most studied mutations in well-established RBPs in cancer as the top three most frequent (in SF3B1, U2AF1, and SRSF2), aside from the putative RBP SMAD4, supporting the usage of raw frequency as a basis for oncogenic potential. Here, SMAD4 is linked to cancer.