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Genetics Home Reference: your guide to understanding genetic conditions
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TSC2

Reviewed June 2010

What is the official name of the TSC2 gene?

The official name of this gene is “tuberous sclerosis 2.”

TSC2 is the gene's official symbol. The TSC2 gene is also known by other names, listed below.

What is the normal function of the TSC2 gene?

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.

How are changes in the TSC2 gene related to health conditions?

lymphangioleiomyomatosis - caused by mutations in the TSC2 gene

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.

tuberous sclerosis complex - caused by mutations in the TSC2 gene

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.

Where is the TSC2 gene located?

Cytogenetic Location: 16p13.3

Molecular Location on chromosome 16: base pairs 2,047,801 to 2,088,711

The TSC2 gene is located on the short (p) arm of chromosome 16 at position 13.3.

The TSC2 gene is located on the short (p) arm of chromosome 16 at position 13.3.

More precisely, the TSC2 gene is located from base pair 2,047,801 to base pair 2,088,711 on chromosome 16.

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 TSC2?

You and your healthcare professional may find the following resources about TSC2 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 TSC2 gene or gene products?

  • PPP1R160
  • TSC2_HUMAN
  • tuberin

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 TSC2?

base pair ; cell ; DNA ; gene ; heterozygosity ; loss of heterozygosity ; mosaicism ; mutation ; protein ; sclerosis ; somatic mutation ; sporadic ; tissue ; tumor

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

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. (http://www.ncbi.nlm.nih.gov/pubmed/10823953?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18408969?dopt=Abstract)
  • Goncharova EA, Krymskaya VP. Pulmonary lymphangioleiomyomatosis (LAM): progress and current challenges. J Cell Biochem. 2008 Feb 1;103(2):369-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17541983?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18466115?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/17099139?dopt=Abstract)
  • Mak BC, Yeung RS. The tuberous sclerosis complex genes in tumor development. Cancer Invest. 2004;22(4):588-603. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15565817?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/20073603?dopt=Abstract)
  • Narayanan V. Tuberous sclerosis complex: genetics to pathogenesis. Pediatr Neurol. 2003 Nov;29(5):404-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14684235?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7249)
  • Rosner M, Hanneder M, Siegel N, Valli A, Hengstschläger 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. (http://www.ncbi.nlm.nih.gov/pubmed/18291711?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/12773162?dopt=Abstract)
  • Yeung RS. Multiple roles of the tuberous sclerosis complex genes. Genes Chromosomes Cancer. 2003 Dec;38(4):368-75. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14566857?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: June 2010
Published: December 16, 2014