Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

     lymphangioleiomyomatosis Mutations in the TSC2 gene 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 mutation 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 mutated version. This situation is called mosaicism. When a mutation occurs in the other copy of the TSC2 gene in certain cells during a woman's lifetime (a somatic mutation), she may develop LAM. tuberous sclerosis complex More than 1,100 mutations 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 mutations insert or delete a small number of DNA building blocks (base pairs) in the TSC2 gene. Other mutations 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 mutated copy of the TSC2 gene in each cell. This mutation prevents the cell from making functional tuberin from that copy of the gene. However, 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 mutation 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 mutated 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 mutation 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.

     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. 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.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• NF-kappaB
• ER-alpha
• GR
• NF-kappaB1
• c-Myc
• TBP
• NF-1
• Brachyury
• TFIID

Tissue specificity:

Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta.

Molecular Function:

• Gtpase Activator Activity
• Phosphatase Binding
• Protein Homodimerization Activity
• Small Gtpase Binding

Biological Processes:

• Cell Cycle Arrest
• Endocytosis
• Heart Development
• Insulin-Like Growth Factor Receptor Signaling Pathway
• Negative Regulation Of Cell Proliferation
• Negative Regulation Of Insulin Receptor Signaling Pathway
• Negative Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Negative Regulation Of Protein Kinase Activity
• Negative Regulation Of Protein Kinase B Signaling
• Negative Regulation Of Tor Signaling
• Negative Regulation Of Wnt Signaling Pathway
• Neural Tube Closure
• Positive Chemotaxis
• Protein Import Into Nucleus
• Protein Kinase B Signaling
• Protein Localization
• Regulation Of Cell Cycle
• Regulation Of Endocytosis
• Regulation Of Insulin Receptor Signaling Pathway
• Regulation Of Small Gtpase Mediated Signal Transduction
• Vesicle-Mediated Transport
• Viral Process

*synonyms