Ataxia telangiectasia mutated (ATM)

The official name of this gene is “ataxia telangiectasia mutated.” ATM is the gene's official symbol. The ATM gene is also known by other names, listed below.

The ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps control the rate at which cells grow and divide. This protein also plays an important role in the normal development and activity of several body systems, including the nervous system and the immune system. Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. DNA can be damaged by agents such as toxic chemicals or radiation. Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information. Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research.

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

ataxia-telangiectasia - caused by mutations in the ATM gene Researchers have identified several hundred mutations in the ATM gene that cause ataxia-telangiectasia. People with this disorder have mutations in both copies of the ATM gene in each cell. Most of these mutations disrupt protein production, resulting in an abnormally small, nonfunctional version of the ATM protein. Cells without any functional ATM protein are hypersensitive to radiation and do not respond normally to DNA damage. Instead of activating DNA repair, the defective ATM protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. This kind of unregulated cell growth can lead to the formation of cancerous tumors. In addition, ATM mutations can allow cells to die inappropriately, particularly affecting cells in a part of the brain involved in coordinating movements (the cerebellum). This loss of brain cells causes the movement problems characteristic of ataxia-telangiectasia.

breast cancer - associated with the ATM gene Researchers have found that having a mutation in one copy of the ATM gene in each cell (particularly in people who have at least one family member with ataxia-telangiectasia) is associated with an increased risk of developing breast cancer. About 1 percent of the United States population carries one mutated copy of the ATM gene in each cell. These genetic changes prevent many of the body's cells from correctly repairing damaged DNA.

People who have only one copy of the ATM gene in each cell due to a gene deletion are also at an increased risk of developing breast cancer. Cells that are missing one copy of the ATM gene produce half the normal amount of ATM protein. A shortage of this protein prevents efficient repair of DNA damage, leading to the accumulation of mutations in other genes. This buildup of mutations is likely to allow cancerous tumors to develop.

other cancers - increased risk from variations of the ATM gene

Research suggests that people who carry one mutated copy of the ATM gene in each cell may have an increased risk of developing several other types of cancer. In particular, some studies have shown that cancers of the stomach, bladder, pancreas, lung, and ovaries occur more frequently in ATM mutation carriers than in people who do not carry these mutations. The results of similar studies, however, have been conflicting. Additional research is needed to clarify which other types of cancer, if any, are associated with ATM mutations.

Where is the ATM gene located?

Cytogenetic Location: 11q22.3 Molecular Location on chromosome 11: base pairs 107,598,768 to 107,745,035

The ATM gene is located on the long (q) arm of chromosome 11 at position 22.3. More precisely, the ATM gene is located from base pair 107,598,768 to base pair 107,745,035 on chromosome 11.

Where can I find additional information about ATM?

You and your healthcare professional may find the following resources about ATM helpful. [Educational resources] - Information pages (5 links) [Gene Reviews] - Clinical summary [Gene Tests] - DNA tests ordered by healthcare professionals

You may also be interested in these resources, which are designed for genetics professionals and researchers. [PubMed] - Recent literature [OMIM] - Genetic disorder catalog [Research Resources] - Tools for researchers (6 links)

[What other names do people use for the ATM gene or gene products?]

• AT1
• ATA
• ataxia telangiectasia mutated (includes complementation groups A, C and D)
• ataxia telangiectasia mutated protein
• ATC
• ATD
• ATDC
• ATE
• ATM_HUMAN
• AT mutated
• AT protein
• human phosphatidylinositol 3-kinase homolog
• serine-protein kinase ATM
• TEL1
• TELO1

See [How are genetic conditions and genes named?] in the Handbook.

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

• [What is DNA?]
• [What is a gene?]
• [How do genes direct the production of proteins?]
• [How can gene mutations affect health and development?]

These links provide additional genetics resources that may be useful.

• [Genetics education]
• [Human Genome Project]
• [Resources for Genetic Researchers]

What glossary definitions help with understanding ATM?

[ataxia] ; [cancer] ; [carrier] ; [cell] ; [cell division] ; [cerebellum] ; [chromosome] ; [deletion] ; [DNA] ; [DNA damage] ; [DNA repair] ; [enzyme] ; [gene] ; [gene deletion] ; [homologs] ; [immune system] ; [kinase] ; [mutation] ; [nervous system] ; [nucleus] ; [ovary] ; [pancreas] ; [population] ; [protein] ; [radiation] ; [serine] ; [stomach] ; [telangiectasia] ; [toxic] ; [tumor] You may find definitions for these and many other terms in the Genetics Home Reference [Glossary]. See also [Understanding Medical Terminology].

References

These sources were used to develop the Genetics Home Reference gene summary on the ATM gene.

• Ahmed M, Rahman N. ATM and breast cancer susceptibility. Oncogene. 2006 Sep 25;25(43):5906-11. Review. PubMed citation
• Bradbury JM, Jackson SP. ATM and ATR. Curr Biol. 2003 Jun 17;13(12):R468. No abstract available. PubMed citation
• Geoffroy-Perez B, Janin N, Ossian K, Lauge A, Croquette MF, Griscelli C, Debre M, Bressac-de-Paillerets B, Aurias A, Stoppa-Lyonnet D, Andrieu N. Cancer risk in heterozygotes for ataxia-telangiectasia. Int J Cancer. 2001 Jul 15;93(2):288-93. PubMed citation
• Gumy-Pause F, Wacker P, Sappino AP. ATM gene and lymphoid malignancies. Leukemia. 2004 Feb;18(2):238-42. Review. PubMed citation
• Hall J. The Ataxia-telangiectasia mutated gene and breast cancer: gene expression profiles and sequence variants. Cancer Lett. 2005 Sep 28;227(2):105-14. Epub 2005 Jan 8. Review. PubMed citation
• Kim JH, Kim H, Lee KY, Choe KH, Ryu JS, Yoon HI, Sung SW, Yoo KY, Hong YC. Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. Hum Mol Genet. 2006 Apr 1;15(7):1181-6. Epub 2006 Feb 23. PubMed citation
• Kitagawa R, Kastan MB. The ATM-dependent DNA damage signaling pathway. Cold Spring Harb Symp Quant Biol. 2005;70:99-109. Review. PubMed citation
• Kurz EU, Lees-Miller SP. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):889-900. Review. PubMed citation
• Lavin MF, Birrell G, Chen P, Kozlov S, Scott S, Gueven N. ATM signaling and genomic stability in response to DNA damage. Mutat Res. 2005 Jan 6;569(1-2):123-32. Review. PubMed citation
• Lavin MF, Kozlov S. DNA damage-induced signalling in ataxia-telangiectasia and related syndromes. Radiother Oncol. 2007 Jun;83(3):231-7. Epub 2007 May 23. Review. PubMed citation
• McKinnon PJ. ATM and ataxia telangiectasia. EMBO Rep. 2004 Aug;5(8):772-6. Review. PubMed citation
• Motoyama N, Naka K. DNA damage tumor suppressor genes and genomic instability. Curr Opin Genet Dev. 2004 Feb;14(1):11-6. Review. PubMed citation
• Prokopcova J, Kleibl Z, Banwell CM, Pohlreich P. The role of ATM in breast cancer development. Breast Cancer Res Treat. 2007 Aug;104(2):121-8. Epub 2006 Oct 24. Review. PubMed citation
• Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, McGuffog L, Evans DG, Eccles D; Breast Cancer Susceptibility Collaboration (UK); Easton DF, Stratton MR, Rahman N. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet. 2006 Aug;38(8):873-5. Epub 2006 Jul 9. PubMed citation
• Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003 Mar;3(3):155-68. Review. PubMed citation
• Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, Easton DF. Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst. 2005 Jun 1;97(11):813-22. PubMed citation
• Yang J, Yu Y, Hamrick HE, Duerksen-Hughes PJ. ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses. Carcinogenesis. 2003 Oct;24(10):1571-80. Epub 2003 Aug 14. Review. PubMed citation