Gain-of-function (GOF) mutations in CTNNB1 (encoding for β-catenin) are one of the major trunk mutational events in HCC and occur mostly as missense mutations in exon 3 at serine and threonine residues or the ubiquitination destruction motif, which interfere with its degradation, leading to constitutive β-catenin activation and target gene transcription13,14. The gene discussed is CTNNB1; the disease is hepatocellular carcinoma.