The TSC2 gene provides instructions for producing a protein called tuberin. Within cells, tuberin interacts with a protein called hamartin, which is produced from the TSC1 gene. These two proteins help control cell growth and division (proliferation) and cell 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
TSC2 gene variants (also known as mutations) 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 variant 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 altered version. This situation is called mosaicism. When a variant occurs in the other copy of the TSC2 gene in certain cells during a woman's lifetime (a somatic variant), she may develop LAM.More About This Health Condition
Tuberous sclerosis complex
More than a thousand variants 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 variants insert or delete a small number of DNA building blocks (base pairs) in the TSC2 gene. Other variants 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 altered copy of the TSC2 gene in each cell. A TSC2 gene variant prevents the cell from making functional tuberin from that copy of the gene. 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 variant 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 altered 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 variant 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, leading to the signs and symptoms of tuberous sclerosis complex.More About This Health Condition
Other Names for This Gene
- tuberous sclerosis 2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- 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
- Dufner Almeida LG, Nanhoe S, Zonta A, Hosseinzadeh M, Kom-Gortat R, Elfferich P, Schaaf G, Kenter A, Kümmel D, Migone N, Povey S, Ekong R, Nellist M. Comparison of the functional and structural characteristics of rare TSC2 variants with clinical and genetic findings. Hum Mutat. 2020 Apr;41(4):759-773. doi: 10.1002/humu.23963. Epub 2019 Dec 19. Citation on PubMed
- Northrup H, Koenig MK, Pearson DA, Au KS. Tuberous Sclerosis Complex. 1999 Jul 13 [updated 2021 Dec 9]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK1220/ Citation on PubMed
- Ramlaul K, Fu W, Li H, de Martin Garrido N, He L, Trivedi M, Cui W, Aylett CHS, Wu G. Architecture of the Tuberous Sclerosis Protein Complex. J Mol Biol. 2021 Jan 22;433(2):166743. doi: 10.1016/j.jmb.2020.166743. Epub 2020 Dec 8. Citation on PubMed
- Rosengren T, Nanhoe S, de Almeida LGD, Schönewolf-Greulich B, Larsen LJ, Hey CAB, Dunø M, Ek J, Risom L, Nellist M, Møller LB. Mutational analysis of TSC1 and TSC2 in Danish patients with tuberous sclerosis complex. Sci Rep. 2020 Jun 18;10(1):9909. doi: 10.1038/s41598-020-66588-4. Citation on PubMed