Our crystal structure revealed the residues that are important in mediating the interaction between SETD2 and hnRNP L. Notably, some of them are mutated in cancer including the critical residue Y257 of hnRNP L, mutating which led to the abolishment of SETD2–hnRNP L interaction, and P2192 which is part of the LLPTP motif which hnRNP L seems to prefer (Supplementary Fig. 7). This evidence concerns the gene HNRNPL and cancer.