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GENATLAS PHENOTYPE
last update : 5/04/2008
Symbol TSC2
Location 16p13.3
Name tuberous sclerosis 2
Corresponding gene TSC2
related resource TSC Variation database
Main clinical features
  • the widespread development of hamartomatous growths, noteworthy in eyes, heart, skin and brain, with seizures, behavioral disorder, renal angiomyolipoma and lymphangioleiomyomatosis in females, with a high risk of mental retardation
  • clinical manifestations include epilepsy, learning difficulties, behavioral problems, skin lesions, renal lesions, usually angiomyolipomata
    • Genetic determination autosomal dominant
    Function/system disorder eye
    neurology
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/loss of function amino-acid substitutions to the central region (outside the GAP domain) disrupting the tuberin-hamartin complex
    frameshift   abnormal protein/loss of function  
    unknown   abnormal protein/loss of function two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to activation of FRAP1 and to subependymal giant cell
    Remark(s) . tuberin (TUB), with a majority (85%) of small mutations after disrupting interaction between hamartin and tuberin and 15% of large deletions and some cases with germine mosaicism
  • loss-of-function mutated tuberin can activate Rac1 and thereby increase reactive oxygen species production
  • mutations in either TSC1 or TSC2 alone can lead to polycystic kidney disease, but renal failure is uncommon (Hartman 2009)
  • loss of TSC2 in tumors causes endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR) (Ozcan 2008)