We illustrate the colocalization of SIX1 and WNT5A proteins within individual cells in Wilms tumor tissue by immunofluorescence, demonstrate SIX1 and SIX1-Q177R enhancement of transcription via putative WNT5A cis-regulatory elements (CREs) in vitro, and provide a mechanistic link to WNT5A upregulation that is attributable to the enhanced DNA-binding affinity of SIX1-Q177R within the WNT5A promoter. The gene discussed is SIX1; the disease is Wilms tumor.