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TSC2 gene

TSC complex subunit 2
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Normal Function

The TSC2 gene provides instructions for producing a protein called tuberin, whose function is not fully understood. Within cells, tuberin interacts with a protein called hamartin, which is produced from the TSC1 gene. These two proteins help control cell growth and size. Proteins that normally prevent cells from growing and dividing too fast or in an uncontrolled way are known as tumor suppressors. Hamartin and tuberin carry out their tumor suppressor function by interacting with and regulating a wide variety of other proteins.

Health Conditions Related to Genetic Changes

Lymphangioleiomyomatosis

Mutations in the TSC2 gene cause most cases of a disorder called lymphangioleiomyomatosis (LAM). This destructive lung disease is characterized by the abnormal overgrowth of smooth muscle-like tissue in the lungs. It occurs almost exclusively in women, causing coughing, shortness of breath, chest pain, and lung collapse.

LAM can occur alone (isolated or sporadic LAM) or in combination with a condition called tuberous sclerosis complex (described below). Researchers suggest that sporadic LAM is caused by a random mutation in the TSC2 gene that occurs very early in development. As a result, some of the body's cells have a normal version of the gene, while others have the mutated version. This situation is called mosaicism. When a mutation occurs in the other copy of the TSC2 gene in certain cells during a woman's lifetime (a somatic mutation), she may develop LAM.

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Tuberous sclerosis complex

More than 1,100 mutations in the TSC2 gene have been identified in individuals with tuberous sclerosis complex, a condition characterized by developmental problems and the growth of noncancerous tumors in many parts of the body. Most of these mutations insert or delete a small number of DNA building blocks (base pairs) in the TSC2 gene. Other mutations change a single base pair in the TSC2 gene or create a premature stop signal in the instructions for making tuberin.

People with TSC2-related tuberous sclerosis complex are born with one mutated copy of the TSC2 gene in each cell. This mutation prevents the cell from making functional tuberin from that copy of the gene. However, enough tuberin is usually produced from the other, normal copy of the TSC2 gene to regulate cell growth effectively. For some types of tumors to develop, a second mutation involving the other copy of the gene must occur in certain cells during a person's lifetime.

When both copies of the TSC2 gene are mutated in a particular cell, that cell cannot produce any functional tuberin. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. A shortage of tuberin also interferes with the normal development of certain cells. In people with TSC2-related tuberous sclerosis complex, a second TSC2 gene mutation typically occurs in multiple cells over an affected person's lifetime. The loss of tuberin in different types of cells disrupts normal development and leads to the growth of tumors in many different organs and tissues.

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Other Names for This Gene

  • PPP1R160
  • TSC2_HUMAN
  • tuberin
  • tuberous sclerosis 2

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6085-90. Citation on PubMed or Free article on PubMed Central
  • Chorianopoulos D, Stratakos G. Lymphangioleiomyomatosis and tuberous sclerosis complex. Lung. 2008 Jul-Aug;186(4):197-207. doi: 10.1007/s00408-008-9087-5. Epub 2008 Apr 12. Review. Citation on PubMed
  • Goncharova EA, Krymskaya VP. Pulmonary lymphangioleiomyomatosis (LAM): progress and current challenges. J Cell Biochem. 2008 Feb 1;103(2):369-82. Review. Citation on PubMed
  • Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J. 2008 Jun 1;412(2):179-90. doi: 10.1042/BJ20080281. Review. Citation on PubMed or Free article on PubMed Central
  • Juvet SC, McCormack FX, Kwiatkowski DJ, Downey GP. Molecular pathogenesis of lymphangioleiomyomatosis: lessons learned from orphans. Am J Respir Cell Mol Biol. 2007 Apr;36(4):398-408. Epub 2006 Nov 10. Review. Citation on PubMed or Free article on PubMed Central
  • Mak BC, Yeung RS. The tuberous sclerosis complex genes in tumor development. Cancer Invest. 2004;22(4):588-603. Review. Citation on PubMed
  • Martignoni G, Pea M, Reghellin D, Gobbo S, Zamboni G, Chilosi M, Bonetti F. Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Arch Pathol Lab Med. 2010 Jan;134(1):33-40. doi: 10.1043/2008-0542-RAR1.1. Citation on PubMed
  • Narayanan V. Tuberous sclerosis complex: genetics to pathogenesis. Pediatr Neurol. 2003 Nov;29(5):404-9. Review. Citation on PubMed
  • Rosner M, Hanneder M, Siegel N, Valli A, Hengstschl√§ger M. The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners. Mutat Res. 2008 Mar-Apr;658(3):234-46. doi: 10.1016/j.mrrev.2008.01.001. Epub 2008 Jan 12. Review. Citation on PubMed
  • Sampson JR. TSC1 and TSC2: genes that are mutated in the human genetic disorder tuberous sclerosis. Biochem Soc Trans. 2003 Jun;31(Pt 3):592-6. Citation on PubMed
  • Yeung RS. Multiple roles of the tuberous sclerosis complex genes. Genes Chromosomes Cancer. 2003 Dec;38(4):368-75. Review. Citation on PubMed
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