A unique missense mutation in the RING domain impairs MID1 E3 ubiquitin ligase activity and localisation and is associated with uncommon Opitz Syndrome-like signs

center dot MID1/TRIM18 is a member of the RING-containing Tripartite Motif family of E3 ubiquitin ligases. center dot MID1 mutations cause X-linked Opitz Syndrome (XLOS), a neurodevelopmental genetic disease. center dot We detected a Cys56Arg substitution in a family with history of midline developmental defects as the first variant identified in MID1 catalytic RING domain. center dot This variant affects MID1 ubiquitin E3 activity and alters MID1 subcellular localisation and microtubule dynamics in a unique manner if compared to the other XLOS-associated mutations. center dot Our data suggest that the relationship between MID1 activity and its cellular distribution is a crucial issue to fully understand MID1 physio-pathological role.