The top six most frequently mutated sites across all cancer types, accounting for 6–25% of all cancer-associated mutations in beta-catenin (Fig 6A, red dots) include the CKI and GSK3B phosphorylation sites (Ser-45, Thr-41, Ser-37, and Ser-33) and two highly conserved residues in the BTRC ubiquitin ligase recognition motif (Asp-32 and Gly-34). Here, BTRC is linked to cancer.