Encyclopedia
TERF1 interacting nuclear factor 2 (TINF2): The TINF2 gene provides instructions for making part of the shelterin protein complex.
- genes
1. Normal Function
The TINF2 gene provides instructions for making part of the shelterin protein complex. This complex consists of a group of proteins that work together to help maintain structures known as telomeres, which are found at the ends of chromosomes. Telomeres help protect chromosomes from abnormally sticking together or breaking down (degrading).
The shelterin complex helps protect telomeres from the cell's DNA repair process. Without the protection of shelterin, the repair mechanism would sense the chromosome ends as abnormal breaks in the DNA sequence and either attempt to join the ends together or initiate cellular self-destruction (apoptosis).
2. Health Conditions Related to Genetic Changes
2.1. Dyskeratosis congenita
At least 15 mutations in the TINF2 gene have been identified in people with dyskeratosis congenita, including a severe form of this disorder called Revesz syndrome. Dyskeratosis congenita 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 TINF2 gene mutations that cause dyskeratosis congenita change single protein building blocks (amino acids) in the TINF2 protein, likely disrupting the function of the protein. The mutations result in dysfunction of the shelterin complex, interfering with its protection of telomeres and leading to reduced telomere length. Shortened telomeres can result in damage to genetic material, causing the cell to stop dividing or to undergo apoptosis.
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
3. Other Names for This Gene
- (TRF1)-interacting nuclear factor 2 variant 1
- TERF1 (TRF1)-interacting nuclear factor 2
- TERF1-interacting nuclear factor 2
- TERF1-interacting nuclear factor 2 isoform 1
- TERF1-interacting nuclear factor 2 isoform 2
- TIN2
- TINF2_HUMAN
- TRF1-interacting nuclear protein 2
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/tinf2
References
- 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.
- Baran I, Nalcaci R, Kocak M. Dyskeratosis congenita: clinical report andreview of the literature. Int J Dent Hyg. 2010 Feb;8(1):68-74. doi:10.1111/j.1601-5037.2009.00364.x. Review.
- Calado RT, Young NS. Telomere maintenance and human bone marrow failure.Blood. 2008 May 1;111(9):4446-55. doi: 10.1182/blood-2007-08-019729.
- Calado RT. Telomeres and marrow failure. Hematology Am Soc Hematol EducProgram. 2009:338-43. doi: 10.1182/asheducation-2009.1.338. Review.
- Chan SS, Chang S. Defending the end zone: studying the players involved inprotecting chromosome ends. FEBS Lett. 2010 Sep 10;584(17):3773-8. doi:10.1016/j.febslet.2010.06.016.
- Kirwan M, Dokal I. Dyskeratosis congenita, stem cells and telomeres. BiochimBiophys Acta. 2009 Apr;1792(4):371-9. doi: 10.1016/j.bbadis.2009.01.010.
- 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.
- Sasa GS, Ribes-Zamora A, Nelson ND, Bertuch AA. Three novel truncating TINF2mutations causing severe dyskeratosis congenita in early childhood. Clin Genet.2012 May;81(5):470-8. doi: 10.1111/j.1399-0004.2011.01658.x.
- Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. TINF2, acomponent of the shelterin telomere protection complex, is mutated indyskeratosis congenita. Am J Hum Genet. 2008 Feb;82(2):501-9. doi:10.1016/j.ajhg.2007.10.004.
- Walne AJ, Dokal I. Advances in the understanding of dyskeratosis congenita. BrJ Haematol. 2009 Apr;145(2):164-72. doi: 10.1111/j.1365-2141.2009.07598.x.
- Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosiscongenita and related bone marrow failure syndromes. Blood. 2008 Nov1;112(9):3594-600. doi: 10.1182/blood-2008-05-153445.
