TERT Gene: History
Please note this is an old version of this entry, which may differ significantly from the current revision.

Telomerase reverse transcriptase: The TERT gene provides instructions for making one component of an enzyme called telomerase.

  • genes

1. Normal Function

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.

2. Health Conditions Related to Genetic Changes

2.1. Idiopathic pulmonary fibrosis

At least 70 mutations in the TERT gene have been identified in people with the progressive lung disease idiopathic pulmonary fibrosis. This condition causes scar tissue (fibrosis) to build up in the lungs, which makes the lungs unable to transport oxygen into the bloodstream effectively. Mutations in the TERT 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 TERT 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. In people with idiopathic pulmonary fibrosis, shorter telomeres are associated with a more severe disease and a quicker decline in lung function. Additional research is needed to confirm 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.

2.2. Dyskeratosis congenita

At least 40 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.


2.3. Cancers

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.

2.4. Other disorders

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.

Breast cancer



3. Other Names for This Gene

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

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/tert


  1. Arish N, Petukhov D, Wallach-Dayan SB. The Role of Telomerase and Telomeres inInterstitial Lung Diseases: From Molecules to Clinical Implications. Int J MolSci. 2019 Jun 19;20(12). pii: E2996. doi: 10.3390/ijms20122996. Review.
  2. Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, Eshleman JR,Cohen AR, Chakravarti A, Hamosh A, Greider CW. Haploinsufficiency of telomerasereverse transcriptase leads to anticipation in autosomal dominant dyskeratosiscongenita. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15960-4.
  3. 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. Telomerasemutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29;356(13):1317-26.
  4. Autexier C, Lue NF. The structure and function of telomerase reversetranscriptase. Annu Rev Biochem. 2006;75:493-517. Review.
  5. Baird DM. Variation at the TERT locus and predisposition for cancer. ExpertRev Mol Med. 2010 May 18;12:e16. doi: 10.1017/S146239941000147X. Review.
  6. Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosiscongenita and related telomere biology disorders. Expert Rev Hematol. 2013Jun;6(3):327-37. doi: 10.1586/ehm.13.23. Review.
  7. 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.
  8. Cao Y, Bryan TM, Reddel RR. Increased copy number of the TERT and TERCtelomerase subunit genes in cancer cells. Cancer Sci. 2008 Jun;99(6):1092-9. doi:10.1111/j.1349-7006.2008.00815.x. Review.
  9. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrentTERT promoter mutations in human melanoma. Science. 2013 Feb 22;339(6122):957-9. doi: 10.1126/science.1229259.
  10. Marrone A, Walne A, Tamary H, Masunari Y, Kirwan M, Beswick R, Vulliamy T,Dokal I. Telomerase reverse-transcriptase homozygous mutations in autosomalrecessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Blood. 2007Dec 15;110(13):4198-205.
  11. 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.
  12. Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, RosenblattRL, Shay JW, Garcia CK. Adult-onset pulmonary fibrosis caused by mutations intelomerase. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7552-7.
  13. Vulliamy TJ, Walne A, Baskaradas A, Mason PJ, Marrone A, Dokal I. Mutations inthe reverse transcriptase component of telomerase (TERT) in patients with bonemarrow failure. Blood Cells Mol Dis. 2005 May-Jun;34(3):257-63.
  14. 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.
  15. Yan S, Han B, Wu Y, Zhou D, Zhao Y. Telomerase gene mutation screening andtelomere overhang detection in Chinese patients with acute myeloid leukemia. LeukLymphoma. 2013 Jul;54(7):1437-41. doi: 10.3109/10428194.2012.729834.
This entry is offline, you can click here to edit this entry!
Video Production Service