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Genetics Home Reference: your guide to understanding genetic conditions
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TERT

Reviewed March 2014

What is the official name of the TERT gene?

The official name of this gene is “telomerase reverse transcriptase.”

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

What is the normal function of the TERT gene?

The TERT gene provides instructions for making one component of an enzyme called telomerase. Telomerase maintains structures called telomeres, which are composed of repeated segments of DNA found at the ends of chromosomes. Telomeres protect chromosomes from abnormally sticking together or breaking down (degrading). In most cells, telomeres become progressively shorter as the cell divides. After a certain number of cell divisions, the telomeres become so short that they trigger the cell to stop dividing or to self-destruct (undergo apoptosis). Telomerase counteracts the shortening of telomeres by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides.

In most types of cells, telomerase is either undetectable or active at very low levels. However, telomerase is highly active in cells that divide rapidly, such as cells that line the lungs and gastrointestinal tract, cells in bone marrow, and cells of the developing fetus. Telomerase allows these cells to divide many times without becoming damaged or undergoing apoptosis. Telomerase is also abnormally active in most cancer cells, which grow and divide without control or order.

The telomerase enzyme consists of two major components that work together. The component produced from the TERT gene is known as hTERT. The other component is produced from a gene called TERC and is known as hTR. The hTR component provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. The hTERT component then adds the new DNA segment to chromosome ends.

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

dyskeratosis congenita - caused by mutations in the TERT gene

At least 18 mutations in the TERT gene have been identified in people with dyskeratosis congenita. This disorder is characterized by changes in skin coloring (pigmentation), white patches inside the mouth (oral leukoplakia), and abnormally formed fingernails and toenails (nail dystrophy). People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions, including cancer and a progressive lung disease called pulmonary fibrosis. Many affected individuals also develop a serious condition called aplastic anemia, also known as bone marrow failure, which occurs when the bone marrow does not produce enough new blood cells.

Most of the TERT gene mutations that cause dyskeratosis congenita change single protein building blocks (amino acids) in the hTERT protein, causing it to be unstable or dysfunctional. The mutations interfere with telomerase function, leading to impaired maintenance of telomeres and reduced telomere length. Cells that divide rapidly are especially vulnerable to the effects of shortened telomeres. As a result, people with dyskeratosis congenita may experience a variety of problems affecting quickly dividing cells in the body such as cells of the nail beds, hair follicles, skin, lining of the mouth (oral mucosa), and bone marrow.

Breakage and instability of chromosomes resulting from inadequate telomere maintenance may lead to genetic changes that allow cells to divide in an uncontrolled way, resulting in the development of cancer in some people with dyskeratosis congenita.

cancers - increased risk from variations of the TERT gene

Mutations in the TERT gene have been associated with an increased risk of various cancers, in particular a type of skin cancer called melanoma and a form of blood cancer called acute myeloid leukemia. Researchers suggest that these mutations may impair telomere maintenance and result in DNA damage. Damage to genes that help control the growth and development of cells can cause uncontrolled cell growth and lead to development of these cancers.

idiopathic pulmonary fibrosis - increased risk from variations of the TERT gene

At least 23 mutations in the TERT gene have been identified in people with the progressive lung disease idiopathic pulmonary fibrosis. Mutations in this gene have been found in cases that run in families (familial pulmonary fibrosis) and, less commonly, in isolated (sporadic) cases. Some individuals with idiopathic pulmonary fibrosis due to TERC gene mutations have family members with other features of dyskeratosis congenita (described above), such as aplastic anemia or cancer.

Mutations in the TERT gene reduce or eliminate the function of telomerase, which allows telomeres to become abnormally short as cells divide. The shortened telomeres likely trigger cells that divide rapidly, such as cells that line the inside of the lungs, to stop dividing or to die prematurely. However, researchers are unsure how shortened telomeres contribute to the progressive scarring and lung damage characteristic of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a complex disease that is probably caused by a combination of genetic and environmental factors. Studies suggest that many affected people with TERT gene mutations may have also been exposed to environmental risk factors, such as cigarette smoke or certain kinds of dust or fumes. It is possible that mutations in the TERT gene increase a person's risk of developing idiopathic pulmonary fibrosis, and then exposure to certain environmental factors can trigger the disease.

other disorders - caused by mutations in the TERT gene

TERT gene mutations have also been found in people with isolated aplastic anemia, a form of bone marrow failure that occurs without the other physical features of dyskeratosis congenita. Researchers suggest that mutations affecting different parts of the telomerase enzyme may account for the absence of these features. Some believe that isolated aplastic anemia caused by TERT gene mutations may actually represent a late-onset form of dyskeratosis congenita in which physical features such as nail dystrophy are mild and may not be noticeable.

Where is the TERT gene located?

Cytogenetic Location: 5p15.33

Molecular Location on chromosome 5: base pairs 1,253,166 to 1,295,046

The TERT gene is located on the short (p) arm of chromosome 5 at position 15.33.

The TERT gene is located on the short (p) arm of chromosome 5 at position 15.33.

More precisely, the TERT gene is located from base pair 1,253,166 to base pair 1,295,046 on chromosome 5.

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 TERT?

You and your healthcare professional may find the following resources about TERT 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 TERT gene or gene products?

  • EST2
  • hEST2
  • TCS1
  • telomerase-associated protein 2
  • telomerase catalytic subunit
  • TERT_HUMAN
  • TP2
  • TRT

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 TERT?

acids ; acute ; acute myeloid leukemia ; anemia ; aplastic anemia ; apoptosis ; bone marrow ; cancer ; catalytic ; cell ; chromosome ; DNA ; DNA damage ; enzyme ; familial ; fetus ; fibrosis ; gastrointestinal ; gene ; idiopathic ; leukemia ; leukoplakia ; melanoma ; mucosa ; myeloid ; pigmentation ; protein ; pulmonary ; risk factors ; sporadic ; subunit ; telomere ; template

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

References

  • Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR, Cohen AR, Chakravarti A, Hamosh A, Greider CW. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15960-4. Epub 2005 Oct 24. (http://www.ncbi.nlm.nih.gov/pubmed/16247010?dopt=Abstract)
  • Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE, Xie M, Vulto I, Phillips JA 3rd, Lansdorp PM, Greider CW, Loyd JE. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29;356(13):1317-26. (http://www.ncbi.nlm.nih.gov/pubmed/17392301?dopt=Abstract)
  • Autexier C, Lue NF. The structure and function of telomerase reverse transcriptase. Annu Rev Biochem. 2006;75:493-517. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16756500?dopt=Abstract)
  • Baird DM. Variation at the TERT locus and predisposition for cancer. Expert Rev Mol Med. 2010 May 18;12:e16. doi: 10.1017/S146239941000147X. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20478107?dopt=Abstract)
  • Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol. 2013 Jun;6(3):327-37. doi: 10.1586/ehm.13.23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23782086?dopt=Abstract)
  • Basel-Vanagaite L, Dokal I, Tamary H, Avigdor A, Garty BZ, Volkov A, Vulliamy T. Expanding the clinical phenotype of autosomal dominant dyskeratosis congenita caused by TERT mutations. Haematologica. 2008 Jun;93(6):943-4. doi: 10.3324/haematol.12317. Epub 2008 May 6. (http://www.ncbi.nlm.nih.gov/pubmed/18460650?dopt=Abstract)
  • Cao Y, Bryan TM, Reddel RR. Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells. Cancer Sci. 2008 Jun;99(6):1092-9. doi: 10.1111/j.1349-7006.2008.00815.x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18482052?dopt=Abstract)
  • Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science. 2013 Feb 22;339(6122):957-9. doi: 10.1126/science.1229259. Epub 2013 Jan 24. (http://www.ncbi.nlm.nih.gov/pubmed/23348506?dopt=Abstract)
  • Marrone A, Walne A, Tamary H, Masunari Y, Kirwan M, Beswick R, Vulliamy T, Dokal I. Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Blood. 2007 Dec 15;110(13):4198-205. Epub 2007 Sep 4. (http://www.ncbi.nlm.nih.gov/pubmed/17785587?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7015)
  • Nishio N, Kojima S. Recent progress in dyskeratosis congenita. Int J Hematol. 2010 Oct;92(3):419-24. doi: 10.1007/s12185-010-0695-5. Epub 2010 Oct 1. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20882440?dopt=Abstract)
  • Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, Rosenblatt RL, Shay JW, Garcia CK. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7552-7. Epub 2007 Apr 25. (http://www.ncbi.nlm.nih.gov/pubmed/17460043?dopt=Abstract)
  • Vulliamy TJ, Walne A, Baskaradas A, Mason PJ, Marrone A, Dokal I. Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure. Blood Cells Mol Dis. 2005 May-Jun;34(3):257-63. (http://www.ncbi.nlm.nih.gov/pubmed/15885610?dopt=Abstract)
  • Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005 Apr 7;352(14):1413-24. (http://www.ncbi.nlm.nih.gov/pubmed/15814878?dopt=Abstract)
  • Yan S, Han B, Wu Y, Zhou D, Zhao Y. Telomerase gene mutation screening and telomere overhang detection in Chinese patients with acute myeloid leukemia. Leuk Lymphoma. 2013 Jul;54(7):1437-41. doi: 10.3109/10428194.2012.729834. Epub 2012 Dec 10. (http://www.ncbi.nlm.nih.gov/pubmed/23157242?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: March 2014
Published: September 15, 2014