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Genetics Home Reference: your guide to understanding genetic conditions
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NBN

Reviewed April 2011

What is the official name of the NBN gene?

The official name of this gene is “nibrin.”

NBN is the gene's official symbol. The NBN gene is also known by other names, listed below.

What is the normal function of the NBN gene?

The NBN gene provides instructions for making a protein called nibrin. This protein is involved in several critical cellular functions, including the repair of damaged DNA.

Nibrin interacts with two other proteins, produced from the MRE11A and RAD50 genes, as part of a larger protein complex. Nibrin regulates the activity of this complex by carrying the MRE11A and RAD50 proteins into the cell's nucleus and guiding them to sites of DNA damage. The proteins work together to mend broken strands of DNA. DNA can be damaged by agents such as toxic chemicals or radiation, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material in preparation for cell division. Repairing DNA prevents cells from accumulating genetic damage that may cause them to die or to divide uncontrollably.

The MRE11A/RAD50/NBN complex interacts with the protein produced from the ATM gene, which plays an essential role in recognizing broken strands of DNA and coordinating their repair. The MRE11A/RAD50/NBN complex helps maintain the stability of a cell's genetic information through its roles in repairing damaged DNA and regulating cell division. Because these functions are critical for preventing the formation of cancerous tumors, nibrin is described as a tumor suppressor.

How are changes in the NBN gene related to health conditions?

Nijmegen breakage syndrome - caused by mutations in the NBN gene

At least 10 mutations in the NBN gene have been found to cause Nijmegen breakage syndrome, a condition characterized by slow growth, recurrent infections, and an increased risk of developing cancer. The NBN gene mutations that cause Nijmegen breakage syndrome typically lead to the production of an abnormally short version of the nibrin protein. The mutation found in most affected individuals, particularly in Slavic populations of Eastern Europe, deletes five DNA building blocks (nucleotides) from the NBN gene (written as 657_661del5). This mutation leads to the production of a shortened version of the nibrin protein called p70-nibrin. This shortened protein is not as effective as normal nibrin in responding to DNA damage, but p70-nibrin does appear to have some residual function.

When breaks in DNA are not repaired properly, genetic damage can accumulate. A buildup of mistakes in DNA can trigger cells to grow and divide abnormally, increasing the risk of cancer in people with Nijmegen breakage syndrome. Nibrin's role in regulating cell division and cell growth (proliferation) is thought to lead to the problems with the immune system that are seen in affected individuals. A lack of functional nibrin results in less immune cell proliferation. A decrease in the amount of immune cells that are produced leads to a malfunctioning immune system. It is unclear how mutations in the NBN gene cause the other features of Nijmegen breakage syndrome.

breast cancer - associated with the NBN gene

Recent studies suggest that certain inherited changes in the NBN gene may be associated with an increased risk of developing breast cancer. The c.657_661del5 mutation that is commonly seen in people with Nijmegen breakage syndrome is thought to increase the risk of breast cancer in people who have one copy of the mutation in each cell. It is estimated that people who have the c.657_661del5 mutation have a threefold increased risk of developing breast cancer compared to individuals who do not have this mutation. A few other mutations in the NBN gene have also been associated with an increased risk of developing breast cancer. Researchers believe that the NBN gene mutations associated with breast cancer prevent nibrin from responding effectively to DNA damage. As defects accumulate in DNA, they can trigger cells to grow and divide uncontrollably, causing cancer.

other cancers - associated with the NBN gene

Inherited mutations in the NBN gene have also been associated with several other types of cancer. Studies in Eastern European populations reported that people with mutations in one copy of the NBN gene in each cell may be more likely to develop prostate cancer, ovarian cancer, an aggressive form of skin cancer (melanoma), or cancer of blood-forming cells (leukemia) than people who do not carry NBN mutations. Cells with a mutation in one copy of the NBN gene do not repair DNA as effectively as cells without these mutations. It is thought that DNA damage accumulates over time, which can trigger cells to grow and divide uncontrollably and increase the risk of developing cancer.

Where is the NBN gene located?

Cytogenetic Location: 8q21

Molecular Location on chromosome 8: base pairs 89,933,335 to 89,984,723

The NBN gene is located on the long (q) arm of chromosome 8 at position 21.

The NBN gene is located on the long (q) arm of chromosome 8 at position 21.

More precisely, the NBN gene is located from base pair 89,933,335 to base pair 89,984,723 on chromosome 8.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about NBN?

You and your healthcare professional may find the following resources about NBN helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the NBN gene or gene products?

  • ATV
  • AT-V1
  • AT-V2
  • Cell cycle regulatory protein p95
  • NBN_HUMAN
  • NBS
  • NBS1
  • Nijmegen breakage syndrome 1
  • p95 protein of the MRE11/RAD50 complex

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding NBN?

cancer ; cell ; cell cycle ; cell division ; cell proliferation ; DNA ; DNA damage ; gene ; immune system ; inherited ; leukemia ; melanoma ; mutation ; nucleus ; ovarian ; proliferation ; prostate ; protein ; radiation ; syndrome ; telomere ; toxic ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Bogdanova N, Feshchenko S, Schürmann P, Waltes R, Wieland B, Hillemanns P, Rogov YI, Dammann O, Bremer M, Karstens JH, Sohn C, Varon R, Dörk T. Nijmegen Breakage Syndrome mutations and risk of breast cancer. Int J Cancer. 2008 Feb 15;122(4):802-6. (http://www.ncbi.nlm.nih.gov/pubmed/17957789?dopt=Abstract)
  • Cheung VG, Ewens WJ. Heterozygous carriers of Nijmegen Breakage Syndrome have a distinct gene expression phenotype. Genome Res. 2006 Aug;16(8):973-9. Epub 2006 Jun 29. (http://www.ncbi.nlm.nih.gov/pubmed/16809669?dopt=Abstract)
  • Cybulski C, Górski B, Debniak T, Gliniewicz B, Mierzejewski M, Masojć B, Jakubowska A, Matyjasik J, Złowocka E, Sikorski A, Narod SA, Lubiński J. NBS1 is a prostate cancer susceptibility gene. Cancer Res. 2004 Feb 15;64(4):1215-9. (http://www.ncbi.nlm.nih.gov/pubmed/14973119?dopt=Abstract)
  • Gene Review: Nijmegen Breakage Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1176/)
  • Heikkinen K, Rapakko K, Karppinen SM, Erkko H, Knuutila S, Lundán T, Mannermaa A, Børresen-Dale AL, Borg A, Barkardottir RB, Petrini J, Winqvist R. RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability. Carcinogenesis. 2006 Aug;27(8):1593-9. Epub 2006 Feb 12. (http://www.ncbi.nlm.nih.gov/pubmed/16474176?dopt=Abstract)
  • Kobayashi J, Antoccia A, Tauchi H, Matsuura S, Komatsu K. NBS1 and its functional role in the DNA damage response. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):855-61. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15279770?dopt=Abstract)
  • Krüger L, Demuth I, Neitzel H, Varon R, Sperling K, Chrzanowska KH, Seemanova E, Digweed M. Cancer incidence in Nijmegen breakage syndrome is modulated by the amount of a variant NBS protein. Carcinogenesis. 2007 Jan;28(1):107-11. Epub 2006 Jul 13. (http://www.ncbi.nlm.nih.gov/pubmed/16840438?dopt=Abstract)
  • Lins S, Kim R, Krüger L, Chrzanowska KH, Seemanova E, Digweed M. Clinical variability and expression of the NBN c.657del5 allele in Nijmegen Breakage Syndrome. Gene. 2009 Nov 1;447(1):12-7. doi: 10.1016/j.gene.2009.07.013. Epub 2009 Jul 25. (http://www.ncbi.nlm.nih.gov/pubmed/19635536?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4683)
  • Pluth JM, Yamazaki V, Cooper BA, Rydberg BE, Kirchgessner CU, Cooper PK. DNA double-strand break and chromosomal rejoining defects with misrejoining in Nijmegen breakage syndrome cells. DNA Repair (Amst). 2008 Jan 1;7(1):108-18. Epub 2007 Oct 4. (http://www.ncbi.nlm.nih.gov/pubmed/17919995?dopt=Abstract)
  • Steffen J, Nowakowska D, Niwińska A, Czapczak D, Kluska A, Piatkowska M, Wiśniewska A, Paszko Z. Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland. Int J Cancer. 2006 Jul 15;119(2):472-5. (http://www.ncbi.nlm.nih.gov/pubmed/16770759?dopt=Abstract)
  • Zhang Y, Zhou J, Lim CU. The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control. Cell Res. 2006 Jan;16(1):45-54. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16467875?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2011
Published: August 25, 2014