TRAF3 and multiminicore myopathy: To examine whether the E3 ligase activity of RNF213 contributes to the K27-linked polyubiquitination of TRAF3, we mutated mouse RNF213 W3974 site homologous with the amino acid W4024 within the human RNF213 RING domain, which is found to be mutated in MMD patients and essential for E3 ligase activity (S7D Fig) [26].