Encyclopedia
TSC complex subunit 1: The TSC1 gene provides instructions for producing a protein called hamartin, whose function is not fully understood.
- genes
1. 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.
2. Health Conditions Related to Genetic Changes
2.1. 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.
2.2. 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.
2.3. 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.
Cholangiocarcinoma
3. Other Names for This Gene
- hamartin
- KIAA0243
- TSC1_HUMAN
- tuberous sclerosis 1
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/tsc1
References
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- Goncharova EA, Krymskaya VP. Pulmonary lymphangioleiomyomatosis (LAM):progress and current challenges. J Cell Biochem. 2008 Feb 1;103(2):369-82.Review.
- Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboardcontrolling cell growth. Biochem J. 2008 Jun 1;412(2):179-90. doi:10.1042/BJ20080281. Review.
- Juvet SC, McCormack FX, Kwiatkowski DJ, Downey GP. Molecular pathogenesis oflymphangioleiomyomatosis: lessons learned from orphans. Am J Respir Cell MolBiol. 2007 Apr;36(4):398-408.
- Knowles MA, Habuchi T, Kennedy W, Cuthbert-Heavens D. Mutation spectrum of the9q34 tuberous sclerosis gene TSC1 in transitional cell carcinoma of the bladder. Cancer Res. 2003 Nov 15;63(22):7652-6.
- Mak BC, Yeung RS. The tuberous sclerosis complex genes in tumor development.Cancer Invest. 2004;22(4):588-603. Review.
- Martignoni G, Pea M, Reghellin D, Gobbo S, Zamboni G, Chilosi M, Bonetti F.Molecular pathology of lymphangioleiomyomatosis and other perivascularepithelioid cell tumors. Arch Pathol Lab Med. 2010 Jan;134(1):33-40. doi:10.1043/2008-0542-RAR1.1.
- Mhawech-Fauceglia P, Cheney RT, Schwaller J. Genetic alterations in urothelialbladder carcinoma: an updated review. Cancer. 2006 Mar 15;106(6):1205-16. Review.
- Pymar LS, Platt FM, Askham JM, Morrison EE, Knowles MA. Bladder tumour-derivedsomatic 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.
- Rosner M, Hanneder M, Siegel N, Valli A, Hengstschläger M. The tuberoussclerosis 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.
- Sampson JR. TSC1 and TSC2: genes that are mutated in the human geneticdisorder tuberous sclerosis. Biochem Soc Trans. 2003 Jun;31(Pt 3):592-6.
- Yeung RS. Multiple roles of the tuberous sclerosis complex genes. GenesChromosomes Cancer. 2003 Dec;38(4):368-75. Review.
