This conclusion was based on the analysis of a single isoleucine to alanine mutation at amino acid 26 (I26A) in the BRCA1 RING domain that abrogates its E3 ligase activity in vitro but maintains the stability of the BRCA1-BARD1 heterodimer, unlike many cancer-causing mutations that impair both E3 ligase activity and heterodimer stability [14, 18, 28–30]. The gene discussed is BRCA1; the disease is cancer.