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Genetics Home Reference: your guide to understanding genetic conditions
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TSC1

Reviewed June 2010

What is the official name of the TSC1 gene?

The official name of this gene is “tuberous sclerosis 1.”

TSC1 is the gene's official symbol. The TSC1 gene is also known by other names, listed below.

What is the normal function of the TSC1 gene?

The TSC1 gene provides instructions for producing a protein called hamartin, whose function is not fully understood. Within cells, hamartin interacts with a protein called tuberin, which is produced from the TSC2 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 TSC1 gene related to health conditions?

lymphangioleiomyomatosis - caused by mutations in the TSC1 gene

Mutations in the TSC1 gene can cause a disorder called lymphangioleiomyomatosis (LAM), although mutations in the TSC2 gene appear to be responsible for most cases of this disorder. This destructive lung disease is caused 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 can be caused by a random mutation in the TSC1 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 TSC1 gene in certain cells during a woman's lifetime (a somatic mutation), she may develop LAM.

tuberous sclerosis complex - caused by mutations in the TSC1 gene

More than 400 mutations in the TSC1 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 involve either small deletions or insertions of DNA in the TSC1 gene. Some mutations create a premature stop signal in the instructions for making hamartin.

People with TSC1-related tuberous sclerosis complex are born with one mutated copy of the TSC1 gene in each cell. This mutation prevents the cell from making functional hamartin from that copy of the gene. However, enough hamartin is usually produced from the other, normal copy of the TSC1 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 TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. A shortage of hamartin also interferes with the normal development of certain cells. In people with TSC1-related tuberous sclerosis complex, a second TSC1 gene mutation typically occurs in multiple cells over an affected person's lifetime. The loss of hamartin in different types of cells disrupts normal development and leads to the growth of tumors in many different organs and tissues.

bladder cancer - associated with the TSC1 gene

Somatic mutations of the TSC1 gene that occur in bladder cells are associated with some cases of bladder cancer. In some of these cells, one copy of the TSC1 gene is missing because the region of chromosome 9 containing the gene has been deleted; the other copy of the gene has a mutation that interferes with its function. As a result, little or no hamartin is produced. A loss of hamartin in bladder cells may allow these cells to grow and divide without control, leading to the formation of a cancerous tumor.

It is unclear why inherited TSC1 gene mutations lead to the noncancerous growths characteristic of tuberous sclerosis complex, while somatic mutations in this gene are associated with the development of cancerous tumors.

other disorders - caused by mutations in the TSC1 gene

Inherited mutations in the TSC1 gene can cause a disorder known as focal cortical dysplasia of Taylor balloon cell type. This disorder involves malformations of the cerebrum, the large, frontal part of the brain that is responsible for thinking and learning. Focal cortical dysplasia causes severe recurrent seizures (epilepsy) in affected individuals.

Where is the TSC1 gene located?

Cytogenetic Location: 9q34

Molecular Location on chromosome 9: base pairs 132,891,347 to 132,944,706

The TSC1 gene is located on the long (q) arm of chromosome 9 at position 34.

The TSC1 gene is located on the long (q) arm of chromosome 9 at position 34.

More precisely, the TSC1 gene is located from base pair 132,891,347 to base pair 132,944,706 on chromosome 9.

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 TSC1?

You and your healthcare professional may find the following resources about TSC1 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 TSC1 gene or gene products?

  • hamartin
  • KIAA0243
  • TSC1_HUMAN

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 TSC1?

cancer ; cell ; cerebrum ; chromosome ; DNA ; dysplasia ; epilepsy ; gene ; heterozygosity ; inherited ; 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

  • 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)
  • Knowles MA, Habuchi T, Kennedy W, Cuthbert-Heavens D. Mutation spectrum of the 9q34 tuberous sclerosis gene TSC1 in transitional cell carcinoma of the bladder. Cancer Res. 2003 Nov 15;63(22):7652-6. (http://www.ncbi.nlm.nih.gov/pubmed/14633685?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)
  • Mhawech-Fauceglia P, Cheney RT, Schwaller J. Genetic alterations in urothelial bladder carcinoma: an updated review. Cancer. 2006 Mar 15;106(6):1205-16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16470587?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/7248)
  • Pymar LS, Platt FM, Askham JM, Morrison EE, Knowles MA. Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms. Hum Mol Genet. 2008 Jul 1;17(13):2006-17. doi: 10.1093/hmg/ddn098. Epub 2008 Apr 7. (http://www.ncbi.nlm.nih.gov/pubmed/18397877?dopt=Abstract)
  • 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 22, 2014