Our analysis of SIX1- and SIX1-Q177R-binding data from Wilms tumors, and our in vitro validation of binding-affinity differences between wild-type and mutant protein – particularly at a promoter element for WNT5A – implicates the enhanced binding affinity of SIX1/2-Q177R at putative CREs in the regulation of expression of these differentially expressed genes. Here, SIX1 is linked to Nephroblastoma.