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Zhou, V. BAP1 Gene. Encyclopedia. Available online: https://encyclopedia.pub/entry/4929 (accessed on 21 December 2024).
Zhou V. BAP1 Gene. Encyclopedia. Available at: https://encyclopedia.pub/entry/4929. Accessed December 21, 2024.
Zhou, Vicky. "BAP1 Gene" Encyclopedia, https://encyclopedia.pub/entry/4929 (accessed December 21, 2024).
Zhou, V. (2020, December 24). BAP1 Gene. In Encyclopedia. https://encyclopedia.pub/entry/4929
Zhou, Vicky. "BAP1 Gene." Encyclopedia. Web. 24 December, 2020.
BAP1 Gene
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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/bap1

BRCA1 associated protein 1

genes

1. Normal Function

The BAP1 gene provides instructions for making a protein called ubiquitin carboxyl-terminal hydrolase BAP1 (shortened to BAP1). This protein functions as a deubiquitinase, which means it removes a molecule called ubiquitin from certain proteins. The presence of ubiquitin molecules on a protein can affect the activity of the protein and its interactions with other proteins. The ubiquitin "tag" also promotes breakdown (degradation) of a protein. By removing ubiquitin, BAP1 helps regulate the function of many proteins involved in diverse cellular processes. The BAP1 protein is thought to help control cell growth and division (proliferation) and cell death. Studies suggest that it is involved in the progression of cells through the step-by-step process they take to replicate themselves (called the cell cycle) and that it plays roles in repairing damaged DNA and controlling the activity of genes.

Although the exact mechanism is unclear, the BAP1 protein acts as a tumor suppressor. Tumor suppressor proteins help prevent cells from growing and dividing too rapidly or in an uncontrolled way.

2. Health Conditions Related to Genetic Changes

2.1. BAP1 tumor predisposition syndrome

Mutations in the BAP1 gene cause BAP1 tumor predisposition syndrome. People with this condition have an increased risk of developing many types of noncancerous (benign) and cancerous (malignant) tumors, particularly certain tumors of the skin (atypical Spitz tumors, cutaneous melanoma, and basal cell carcinoma); eyes (uveal melanoma); kidneys (clear cell renal cell carcinoma); and a tissue called the mesothelium that lines the chest, abdomen, and internal organs (malignant mesothelioma). Researchers are still determining whether other forms of cancer are linked to BAP1 tumor predisposition syndrome.

Affected individuals inherit a mutation in one copy of the BAP1 gene. These mutations, which are present in essentially every cell of the body, are classified as germline mutations. Most germline BAP1 gene mutations lead to an abnormally short BAP1 protein that is likely broken down prematurely. Other germline mutations change single protein building blocks (amino acids) in the BAP1 protein and likely impair its function. In most cases, a second, non-inherited (somatic) mutation occurs in the normal copy of the gene in cells that give rise to tumors. Together, the germline and somatic mutations lead to a loss of BAP1 protein function in tumor cells.

Reduction or loss of this protein's function likely prevents the removal of ubiquitin molecules from certain proteins. Although it is unclear exactly how changes in BAP1 function lead to BAP1 tumor predisposition syndrome, researchers speculate that altered activity of proteins normally regulated by BAP1 deubiquitination may promote cell proliferation or survival, resulting in tumor formation.

2.2. Cholangiocarcinoma

Cholangiocarcinoma

2.3. Melanoma

Melanoma

2.4. Other cancers

Somatic BAP1 gene mutations have been found in uveal melanoma, malignant mesothelioma, and clear cell renal cell carcinoma tumors in the absence of a germline BAP1 gene mutation. In these cases, the cancers occur in people with no family history of the cancer and are considered sporadic. Affected individuals do not develop additional tumor types associated with BAP1 tumor predisposition syndrome (described above).

3. Other Names for This Gene

  • BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)
  • cerebral protein 6
  • cerebral protein-13
  • HUCEP-13
  • hucep-6
  • KIAA0272
  • ubiquitin carboxyl-terminal hydrolase BAP1
  • UCHL2

References

  1. Alakus H, Yost SE, Woo B, French R, Lin GY, Jepsen K, Frazer KA, Lowy AM,Harismendy O. BAP1 mutation is a frequent somatic event in peritoneal malignantmesothelioma. J Transl Med. 2015 Apr 16;13:122. doi: 10.1186/s12967-015-0485-1.
  2. Daou S, Hammond-Martel I, Mashtalir N, Barbour H, Gagnon J, Iannantuono NV,Nkwe NS, Motorina A, Pak H, Yu H, Wurtele H, Milot E, Mallette FA, Carbone M,Affar el B. The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates CellProliferation and Is Disrupted in Cancer. J Biol Chem. 2015 Nov27;290(48):28643-63. doi: 10.1074/jbc.M115.661553.
  3. Eletr ZM, Wilkinson KD. An emerging model for BAP1's role in regulating cellcycle progression. Cell Biochem Biophys. 2011 Jun;60(1-2):3-11. doi:10.1007/s12013-011-9184-6. Review.
  4. Jensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, Ishov AM,Tommerup N, Vissing H, Sekido Y, Minna J, Borodovsky A, Schultz DC, Wilkinson KD,Maul GG, Barlev N, Berger SL, Prendergast GC, Rauscher FJ 3rd. BAP1: a novelubiquitin hydrolase which binds to the BRCA1 RING finger and enhancesBRCA1-mediated cell growth suppression. Oncogene. 1998 Mar 5;16(9):1097-112.
  5. Kumar R, Taylor M, Miao B, Ji Z, Njauw JC, Jönsson G, Frederick DT, Tsao H.BAP1 has a survival role in cutaneous melanoma. J Invest Dermatol. 2015Apr;135(4):1089-1097. doi: 10.1038/jid.2014.528.
  6. Matatall KA, Agapova OA, Onken MD, Worley LA, Bowcock AM, Harbour JW. BAP1deficiency causes loss of melanocytic cell identity in uveal melanoma. BMCCancer. 2013 Aug 5;13:371. doi: 10.1186/1471-2407-13-371.
  7. Peña-Llopis S, Vega-Rubín-de-Celis S, Liao A, Leng N, Pavía-Jiménez A, Wang S,Yamasaki T, Zhrebker L, Sivanand S, Spence P, Kinch L, Hambuch T, Jain S, LotanY, Margulis V, Sagalowsky AI, Summerour PB, Kabbani W, Wong SW, Grishin N,Laurent M, Xie XJ, Haudenschild CD, Ross MT, Bentley DR, Kapur P, Brugarolas J.BAP1 loss defines a new class of renal cell carcinoma. Nat Genet. 2012 Jun10;44(7):751-9. doi: 10.1038/ng.2323. Erratum in: Nat Genet. 2012 Sep;44(9):1072.
  8. Royer-Bertrand B, Torsello M, Rimoldi D, El Zaoui I, Cisarova K,Pescini-Gobert R, Raynaud F, Zografos L, Schalenbourg A, Speiser D, Nicolas M,Vallat L, Klein R, Leyvraz S, Ciriello G, Riggi N, Moulin AP, Rivolta C.Comprehensive Genetic Landscape of Uveal Melanoma by Whole-Genome Sequencing. Am J Hum Genet. 2016 Nov 3;99(5):1190-1198. doi: 10.1016/j.ajhg.2016.09.008.
  9. Ventii KH, Devi NS, Friedrich KL, Chernova TA, Tighiouart M, Van Meir EG,Wilkinson KD. BRCA1-associated protein-1 is a tumor suppressor that requiresdeubiquitinating activity and nuclear localization. Cancer Res. 2008 Sep1;68(17):6953-62. doi: 10.1158/0008-5472.CAN-08-0365.
  10. Yu H, Pak H, Hammond-Martel I, Ghram M, Rodrigue A, Daou S, Barbour H, CorbeilL, Hébert J, Drobetsky E, Masson JY, Di Noia JM, Affar el B. Tumor suppressor anddeubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci US A. 2014 Jan 7;111(1):285-90. doi: 10.1073/pnas.1309085110.
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Subjects: Genetics & Heredity
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Vicky Zhou
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Entry Collection: MedlinePlus
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Update Date: 24 Dec 2020
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