What is 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.
What are TSC1 and TSC2 genes?
Tuberous sclerosis proteins 1 and 2, also known as TSC1 (hamartin) and TSC2 (tuberin), form a protein-complex. The encoding two genes are TSC1 and TSC2. The complex is known as a tumor suppressor. Mutations in these genes can cause tuberous sclerosis complex.
What is the difference between TSC1 and TSC2?
Thus, TSC1 has a role in stabilizing the complex, while TSC2 has the GTPase activity. For this reason, inactivating mutations in either gene give rise to the same clinical disorder. Clearly, both proteins play pivotal roles in several processes that are crucial for normal brain development.
Is TSC2 worse than TSC1?
In general, TSC2 disease was more severe than TSC1, with more subependymal giant cell astrocytomas and angiomyolipomas, higher incidence of pharmacoresistant epileptic seizures, and more severe neuropsychiatric disorders.
How does TSC2 inhibit RHEB?
A proposed model of Rheb functions downstream of TSC1/TSC2 and upstream of mTOR. TSC2 acts as a GAP to inactivate Rheb by directly stimulating GTP hydrolysis. Rheb stimulates mTOR. Nutrient and cellular energy status signals through Rheb, whereas osmotic stress signals independently of Rheb.
Where is TSC2?
TSC is caused by a mutation in the DNA of either the TSC1 or TSC2 gene. The TSC1 gene is found on chromosome 9 and codes for the protein called hamartin. The TSC2 gene is found on chromosome 16 and codes for the protein called tuberin.
What activates TSC2?
TSC2 was found to be phosphorylated on Ser1254 by MAPKAP kinase-2, which is activated downstream of p38 MAPK (mitogen-activated protein kinase) [110].
What does the TSC1 gene do?
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.
Is TSC1 or TSC2 more common?
In sporadic cases, TSC2 mutations are 2–10 times more common than TSC1 mutations. In contrast, in multi-generation families segregating TSC, approximately half show linkage to each of the genes.
What does the mTOR pathway do?
The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism.
Is tuberous sclerosis complex autosomal dominant or recessive?
Tuberous sclerosis complex has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and other problems with development.
What does TSC2 stand for?
Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the TSC2 gene.
The 5.5-kb TSC2 transcript was found to be widely expressed, and its protein product, designated tuberin, to have a region of homology to the GTPase-activating protein GAP3. The TSC gene on chromosome 16 was originally designated TSC4.
Which genetic mutations are associated with tuberous sclerosis complex (TSC)?
Two pathogenic mutations in TSC1 and one in TSC2 genes were identified in patients with tuberous sclerosis complex; the patient with TSC2 mutation manifested a more severe clinical phenotype Novel missense mutation in the exon 19 of the TSC2 gene is associated with tuberous sclerosis.
What is the effect of TSC2 mutations on iPSC-derived neurons?
Biallelic mutations in TSC2 resulted in elevated neuronal activity and up-regulation of cell adhesion genes in iPSC-derived neurons.
Can TSC2 exons 25 and 31 cause classical TSC?
Our evidence suggests that variants in TSC2 exons 25 or 31 are very unlikely to cause classical TSC, although a role for these exons in tissue/stage specific development cannot be excluded. In children with tuberous sclerosis complex, nonsense mutations in the TSC2 gene had a correlation with autistic behavior.