Pedigrees of STUB1 index patients, and location and conservation of STUB 1 mutations. (A) Pedigrees of families #1 and 2 reveal consanguinity with parents being first degree cousins. Family #3 shows two affected siblings. (B) The protein structure shows that the p.Met240Thr variant is located in the U-box domain of CHIP, whereas the p.Leu123Val, p.Ala79Thr and Ala79Asp variants are located in the tetratricopeptide-repeat (TPR) domain. All variants are highly conserved across species.