Reviewed April 2011
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 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 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. hTR provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. hTERT 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 10 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, 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 the function of the telomerase complex, 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.
- idiopathic pulmonary fibrosis - increased risk from variations of the TERT gene
About a dozen 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.
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 have also been exposed to environmental risk factors, such as cigarette smoke or certain kinds of dust or fumes. It is likely that mutations in the TERT gene increase a person's risk of developing idiopathic pulmonary fibrosis, and then exposure to certain environmental factors triggers 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 complex 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 1,253,281 to 1,295,161
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 1,253,281 to base pair 1,295,161 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.
Educational resources - Information pages
- Madame Curie Bioscience Database (2000-2011): Components of Human Telomerase (http://www.ncbi.nlm.nih.gov/books/NBK5962/)
- Molecular Biology of the Cell (fourth edition, 2002): Telomerase Replicates the Ends of Chromosomes (http://www.ncbi.nlm.nih.gov/books/NBK26826/)
- The Cell: A Molecular Approach (second edition, 2000): Telomeres and Telomerase: Replicating the Ends of Chromosomes (http://www.ncbi.nlm.nih.gov/books/NBK9940/)
Gene Reviews - Clinical summary
- Gene Review: Dyskeratosis Congenita (http://www.ncbi.nlm.nih.gov/books/NBK22301/)
- Gene Review: Familial Pulmonary Fibrosis (http://www.ncbi.nlm.nih.gov/books/NBK1230/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for TERT (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7015%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((TERT%5BTI%5D)%20OR%20(telomerase%20reverse%20transcriptase%5BTI%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- APLASTIC ANEMIA APLASTIC ANEMIA, SUSCEPTIBILITY TO, INCLUDED (http://omim.org/entry/609135)
- DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT, 1 (http://omim.org/entry/127550)
- TELOMERASE REVERSE TRANSCRIPTASE (http://omim.org/entry/187270)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_TERT.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/7015)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=7015)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=11730)
- Telomerase Database (http://telomerase.asu.edu/)
What other names do people use for the TERT gene or gene products?
- telomerase-associated protein 2
- telomerase catalytic subunit
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?
aplastic anemia ;
bone marrow ;
risk factors ;
You may find definitions for these and many other terms in the Genetics Home Reference
- 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 M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet. 2009;10:45-61. doi: 10.1146/annurev-genom-082908-150046. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19405848?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)
- 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)
- Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009 Dec 10;361(24):2353-65. doi: 10.1056/NEJMra0903373. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20007561?dopt=Abstract)
- Calado RT. Telomeres and marrow failure. Hematology Am Soc Hematol Educ Program. 2009:338-43. doi: 10.1182/asheducation-2009.1.338. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20008219?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)
- Cronkhite JT, Xing C, Raghu G, Chin KM, Torres F, Rosenblatt RL, Garcia CK. Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Oct 1;178(7):729-37. doi: 10.1164/rccm.200804-550OC. Epub 2008 Jul 17. (http://www.ncbi.nlm.nih.gov/pubmed/18635888?dopt=Abstract)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/7015)
- Kirwan M, Dokal I. Dyskeratosis congenita, stem cells and telomeres. Biochim Biophys Acta. 2009 Apr;1792(4):371-9. doi: 10.1016/j.bbadis.2009.01.010. Epub 2009 Feb 7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19419704?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)
- 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)
- Walne AJ, Dokal I. Advances in the understanding of dyskeratosis congenita. Br J Haematol. 2009 Apr;145(2):164-72. doi: 10.1111/j.1365-2141.2009.07598.x. Epub 2009 Feb 4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19208095?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)
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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.