BAP1 Gene

The BAP1 gene (BAP1 stands for "BRCA1-associated protein 1") is a protein-coding gene located on chromosome 3p21.1. The BAP1 gene belongs to the ubiquitin C-terminal hydrolase subfamily, which is involved in the removal of ubiquitin from proteins. The encoded enzyme , is a deubiquitylase, binds to BRCA1 (breast cancer type 1 susceptibility protein) through its RING finger domain and acts as a tumor suppressor. In addition, the enzyme may be involved in the regulation of transcription, cell cycle and growth, DNA damage response, and chromatin dynamics. Deubiquitylase BAP1 is an important regulator of many cancer-associated signaling pathways. It is a deubiquitinating enzyme that plays a key role in chromatin by mediating the deubiquitination of histone H2A and HCFC1 (Okino Y et al. 2015).Furthermore, the enzyme acts as a regulator of cell growth by mediating the deubiquitination of N-terminal and C-terminal HCFC1 chains, with some specificity toward 'Lys-48'-linked polyubiquitin chains compared to 'Lys-63'-linked polyubiquitin chains (Machida YJ et al. 2009).

Germline mutations in this gene may be associated with tumor predisposition syndrome (TPDS), which involves an increased risk of cancers such as malignant mesothelioma, uveal melanoma and cutaneous melanoma.

Diseases associated with BAP1 include:

• Wiesner's nevus
• Kury-Isidor syndrome

and

• Bap1 tumor predisposition syndrome.

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10. Wiesner T et al. (2016) Genomic aberrations in spitzoid melanocytic tumors and their implications for diagnosis, prognosis and therapy. Pathology 48:113-131.