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TSC1 gene

TSC complex subunit 1
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Normal Function

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.

Health Conditions Related to Genetic Changes

Lymphangioleiomyomatosis

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.

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Tuberous sclerosis complex

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.

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Cholangiocarcinoma

MedlinePlus Genetics provides information about Cholangiocarcinoma

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Other disorders

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.

Other Names for This Gene

  • hamartin
  • KIAA0243
  • TSC1_HUMAN
  • tuberous sclerosis 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

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. 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
  • 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. Citation on PubMed
  • 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
  • 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. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • 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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