The BUB1B gene provides instructions for making a protein called BUBR1, which is important for proper chromosome separation during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. The sets of chromosomes align within the cell, with each chromatid attached to a structure called a spindle microtubule; when all chromatids are correctly attached, the spindle microtubule pulls the two halves of the chromatid pair to opposite sides of the cell. The cell then divides in two such that each new cell contains one complete set of chromosomes.
The BUBR1 protein helps ensure that each sister chromatid is attached to a spindle microtubule. If any chromatids remain unattached, the protein prevents cell division.
Health Conditions Related to Genetic Changes
Mosaic variegated aneuploidy syndrome
More than a dozen mutations in the BUB1B gene have been found to cause mosaic variegated aneuploidy (MVA) syndrome type 1. This condition is characterized by cells with abnormal numbers of chromosomes, a situation known as aneuploidy. Affected individuals grow slowly and have an unusually small head size (microcephaly) and an increased risk of developing cancer in childhood.
MVA syndrome type 1 occurs when both copies of the BUB1B gene have mutations. These mutations reduce the amount of BUBR1 protein in cells or impair the protein's ability to function. A shortage of functioning BUBR1 protein leads to errors in the distribution of chromatids during cell division. Without BUBR1 protein, cell division can proceed, even if all the chromatids are not attached to spindle microtubules. Unattached chromatids are not positioned correctly for separation, and the resulting cells have abnormal numbers of chromosomes.
Research suggests that impairment of the process that delays cell division until the correct time underlies the increased risk of cancer in MVA syndrome, although the mechanism is not completely understood. It is also unclear how BUB1B gene mutations or aneuploidy leads to the other features of MVA syndrome. Researchers speculate that the abnormal cells undergo self-destruction (apoptosis). The signs and symptoms of MVA syndrome may be due to the loss of cells from various tissues during early development.More About This Health Condition
Mutations in the BUB1B gene can also cause a related problem with chromosomes called premature chromatid separation trait. Although individuals with this trait have chromosome abnormalities that indicate trouble with normal chromosome separation during cell division, affected individuals usually have no health problems related to the trait. This trait occurs in individuals with a genetic change in one of the two copies of the BUB1B gene.
Other Names for This Gene
- BUB1B, mitotic checkpoint serine/threonine kinase
- budding uninhibited by benzimidazoles 1 homolog beta
- MAD3/BUB1-related protein kinase
- mitotic checkpoint kinase MAD3L
- mitotic checkpoint serine/threonine-protein kinase BUB1 beta
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Garcia-Castillo H, Vasquez-Velasquez AI, Rivera H, Barros-Nunez P. Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: delineation of clinical subtypes. Am J Med Genet A. 2008 Jul 1;146A(13):1687-95. doi: 10.1002/ajmg.a.32315. Citation on PubMed
- Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, Mehes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004 Nov;36(11):1159-61. doi: 10.1038/ng1449. Epub 2004 Oct 10. Citation on PubMed
- Kapanidou M, Lee S, Bolanos-Garcia VM. BubR1 kinase: protection against aneuploidy and premature aging. Trends Mol Med. 2015 Jun;21(6):364-72. doi: 10.1016/j.molmed.2015.04.003. Epub 2015 May 8. Citation on PubMed
- Matsuura S, Matsumoto Y, Morishima K, Izumi H, Matsumoto H, Ito E, Tsutsui K, Kobayashi J, Tauchi H, Kajiwara Y, Hama S, Kurisu K, Tahara H, Oshimura M, Komatsu K, Ikeuchi T, Kajii T. Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am J Med Genet A. 2006 Feb 15;140(4):358-67. doi: 10.1002/ajmg.a.31069. Citation on PubMed
- Suijkerbuijk SJ, van Osch MH, Bos FL, Hanks S, Rahman N, Kops GJ. Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy. Cancer Res. 2010 Jun 15;70(12):4891-900. doi: 10.1158/0008-5472.CAN-09-4319. Epub 2010 Jun 1. Citation on PubMed or Free article on PubMed Central
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