The enriched E3 ligases included Dtx3l, which forms a complex with PARP9 and plays a role in DNA damage and antiviral responses (Zhang et al, 2015); RNF149, an uncharacterised RING ligase; RNF213, a 591 kDa multi‐domain protein which has been implicated in angiogenesis, Moyamoya disease, the sensing of ISGylated proteins (Thery et al, 2021) and the ubiquitylation of LPS of intracellular bacteria (Otten et al, 2021), and the RING E3 ligase RNF115 (also called BCA2 or Rabring7) (Fig 3A). This evidence concerns the gene RNF213 and Moyamoya disease.