PMC

The three-step multidisciplinary (A) flowchart showing the major up-to-date clinical-related approaches for early detection of BAP1 tumor predisposition syndrome (B).

(A) Functional domains and regions of interaction of the 729 a.a BAP1 protein, consisting of an N-terminal UCH domain (1–250), an HCF-1-binding domain (HBM, 363–366), and a two-part NLS (656–661 and 717–722). Simplified BAP1 interaction with BARD1 (182–365), HCF-1 (365–385), BRCA1 (596–721) is also illustrated. Numbers at the beginning and at the end refer to amino acids positions. (B) Distribution of BAP1 mutations in UM, MM, and RCC specimens to date. Inactivating germline mutations identified in previous studies,,–,,,,– are indicated by arrows. Reported somatic missense mutations (SM – blue I) and indels (SI—red*) from UM specimens (COSMIC database; http://www.sanger.ac.uk/genetics/CGP/cosmic/) and germline variants (black lines) from other families are also shown.