In the absence of β-catenin, TCF3 binds to CtBP co-repressor and it acts as a transcriptional repressor.51,52 A motif-breaking S504P mutation, found in a large intestine carcinoma sample (COSMIC), may be responsible for the loss of regulation imposed by CtBP for the repressor activity of TCF3. The gene discussed is TCF3; the disease is colorectal carcinoma.