BAP1 (BRCA1 associated protein-1) is a histone deubiquitinase, with the ubiquitin C-terminal hydrolase (UCH) domain located at its N-terminal domain. This gene is thought to be a tumor suppressor gene that functions in the BRCA1 growth control pathway. Inactivating mutations of the BAP1 gene have been reported in 10–15% of ccRCCs. In addition to a potentially critical role for BAP1 inactivation in epigenetic deregulation in ccRCC, BAP1 has been found to promote DNA double-strand break repair by homologous recombination, thereby adding to its tumor suppressor function. Multiple studies have revealed that, in a substantial portion of ccRCC tumors with BAP1 mutations, the mutations are subclonal and the protein losses are focal. Interestingly, in ccRCC tumors, the mutations of BAP1 and PBRM1 are largely mutually exclusive. BAP1 protein loss has been associated with advanced clinical stage, higher tumor grade, shorter median survival, worse cancer-specific survival and advanced clinical stage.

This gene is a known cancer gene.

This gene is a known cancer gene.