Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TSC1 contributors: mct/npt/shn - updated : 02-10-2015
HGNC name tuberous sclerosis 1
HGNC id 12362
Corresponding disease
FCDBC focal cortical dysplasia of Taylor balloon cell type
TSC1 tuberous sclerosis 1
Location 9q34.13      Physical location : 135.766.734 - 135.820.020
Synonym name
  • hamartin
  • tumor suppressor
  • Synonym symbol(s) TSC, KIAA0243, TS, TUS, LAM, MGC86987
    DNA
    TYPE functioning gene
    STRUCTURE 53.29 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    text structure a 521-bp fragment surrounding the TSS (transcription start site) exhibits the characteristics of a CpG island which overlaps with the promoter region
    MAPPING cloned Y linked N status provisional
    Map cen - D9S1847 - D9S1830 - TSC1 TSC1 - D9S915 - D9S164 - qter
    Physical map
    NTNG2 9q34 netrin G2 KIAA0625 9q25.3-q34.1 netrin G2 TTF1 9q34.13 transcription termination factor, RNA polymerase I LOC389799 9 hypothetical gene supported by AK128819 BARHL1 9q34 BarH-like 1 (Drosophila) DDX31 9q34.3 DEAD (Asp-Glu-Ala-Asp) box polypeptide 31 GTF3C4 9q34.3 general transcription factor IIIC, polypeptide 4, 90kDa FLJ32704 9q34.3 hypothetical protein FLJ32704 C9orf9 9q34 chromosome 9 open reading frame 9 TSC1 9q34.1-q34.2 tuberous sclerosis 1 GFI1B 9q34.13 growth factor independent 1B (potential regulator of CDKN1A, translocated in CML) LOC158078 9q34 eukaryotic translation elongation factor 1 alpha 1 pseudogene LOC389801 9 LOC389801 GTF3C5 9q34 general transcription factor IIIC, polypeptide 5, 63kDa CEL 9q34.2 carboxyl ester lipase (bile salt-stimulated lipase) CELP 9q34.2-q34.3 carboxyl ester lipase pseudogene RALGDS 9q34.1-q34.2 ral guanine nucleotide dissociation stimulator FS 9q34 ral guanine nucleotide dissociation stimulator OBP2B 9q34 ral guanine nucleotide dissociation stimulator LOC286310 9q34.3 similar to Von Ebners gland protein precursor (VEG protein) (Tear prealbumin) (TP) (Tear lipocalin) (Lipocalin 1) ABO 9q34.1-q34.2 ABO blood group (transferase A, aplha 1-3-N-acetylgalactosaminyltransferase; transferase B, alpha 1-3galactosyltransferase) LOC392396 9 similar to Von Ebners gland protein precursor (VEG protein) (Tear prealbumin) (TP) (Tear lipocalin) (Lipocalin 1) SURF6 9q34.2 surfeit 6 SURF5 9q34.2 surfeit 5 RPL7A 9q34.2 ribosomal protein L7a SURF1 9q34.2 surfeit 1 SURF2 9q34.2 surfeit 2 SURF4 9q34.2 surfeit 4 ADAMTS13 9q34 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 13 C9orf7 9q34 chromosome 9 open reading frame 7 SLC2A6 9q34 solute carrier family 2 (facilitated glucose transporter), member 6
    RNA
    TRANSCRIPTS type messenger
    text alternate splicing in the 5'utr
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 8626 129.6 1164 - 1998 9809973
    - - 8623 - 1163 - 1998 9809973
    - - 8473 - 1113 - 1998 9809973
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Endocrinepancreas    
    Lymphoid/Immunespleen   highly
    Reproductivefemale systembreastmammary gland highly
    Respiratorylung    
    Urinarykidney    
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte
    Nervousglia
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    cell cycle     cell cycle, G1
    Text placenta, kidney cells
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • a transmembrane segment
  • a coiled-coil domain inhibited by the presence of tuberin myosin tail
  • N-terminus containing two potential Plk1-binding sites (T310 and S332)
  • HOMOLOGY
    interspecies ortholog to Tsc1, Mus musculus
    ortholog to Tsc1, Rattus norvegicus
    ortholog to TSC1, Pan troglodytes
    ortholog to tsc1, Danio rerio
    Homologene
    FAMILY
    CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text localized to the basal body of the primary cilium (Hartman 2009)
    basic FUNCTION
  • putative growth suppressor gene
  • restriction of tissue growth and reduction of cell size and cell proliferation
  • playing an important role for astrocytes growth control
  • involved in the regulation of centrosome duplication
  • key roles of TSC1/TSC2 in neuronal polarity, suggest a common pathway regulating polarization/growth in neurons and cell size in other tissues (Choi 2008)
  • TSC1-TSC2 complex inhibits MTORC1 and activates MTORC2, which through different mechanisms promotes Akt activation (Huang 2008)
  • with TSC2, function as a heterodimer to inhibit the activity of the mammalian target of rapamycin complex 1 (MTORC1) (Hartman 2009)
  • regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway (Hartman 2009)
  • important role in unfolded protein response and cell survival
  • important role for the TSC1 gene during GABAergic interneuron development, function, and possibly migration
  • is critical for T-cell anergy, by inhibiting MTOR signaling through both ICOS-dependent and -independent mechanisms
  • regulates likely cell polarity-associated formation of actin fibers through the spatial regulation of Rho family of small GTPases
  • novel function of MTOR in regulating potassium homeostasis, demonstrating that loss of TSC1 and activation of MTOR results in dedifferentiation and dysfunction of the collecting ducts and causes hyperkalemia
  • acts as an important checkpoint for maintaining immune homeostasis by regulating cell fate determination
  • TSC1-MTOR signaling contributes to the brown-to-white adipocyte phenotypic switch
  • TSC1 and TSC2 regulate the activity of small GTPases RHOA and RAC1, stress fiber formation and cell adhesion in a reciprocal manner
  • TSC1 and TSC2 differentially regulate actin stress fiber formation and cell migration, but only TSC2 loss promotes MTOR- and CTRC2-dependent pro-migratory cell phenotype
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text negative regulation
    PATHWAY
    metabolism
    signaling
    PI3K pathway
    a component
  • protein constituent of transmembrane
  • TSC1/2 complex has been found to play a crucial role in an evolutionarily-conserved signaling pathway that regulates cell growth: the MTOR pathway
  • TSC1-TSC2-TBC1D7 (TSC-TBC) complex is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • heterodimerizing with TSC2 (
  • ezrin-radixin-moesin, ERM (
  • G2/M cyclin-dependent kinase CDK1 and cyclins A and B (
  • Akt/PKB (
  • neurofilament light chain (
  • peptidylglycine alpha-amidating monooxygenase, PAM (
  • tuberin (TBR) through its coiled-coil domain, to form a complex inhibiting cell growth by antagonizing FRAP1
  • NEFL (anchoring to the actin cytoskeleton)
  • p27
  • dedicator of cytokinesis 7, DOCK7
  • polo-like kinase 1, PLK1 (
  • TBC1 domain family, member 7, TBC7 (
  • TBC1D7 in lung cancer cells (Sato 2010)
  • enhancing MTOR activity via ablation of its negative regulator tuberous sclerosis 1 (TSC1) impaired Dendritic cells development, associated with defective cell survival and proliferation
  • HAP1 is a novel functional partner of TSC1
  • link between HAP1 and TSC1 that regulates neuronal MTOR signaling and neuronal morphogenesis
  • TSC1, TSC2, negatively regulates the mammalian target of rapamycin complex 1 (MTOR) a master regulator of protein synthesis, cell growth and autophagy
  • cell & other
    REGULATION
    Other phosphorylated by CDC2/cyclin B1 during the G(2)/M phase of the cell cycle
    ASSOCIATED DISORDERS
    corresponding disease(s) TSC1 , FCDBC
    related resource TSC Variation database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral germinal mutation      
    in pulmonary lymphangioleiomyomatosis
    tumoral somatic mutation      
    in renal angiomyolipoma, clear cell renal carcinoma and bladder carcinoma
    tumoral   LOH    
    in transitional cell carcinoma of the bladder
    tumoral   LOH    
    in hamartoma
    tumoral       loss of function
    in hamartoma, in kidney tumor
    tumoral somatic mutation     loss of function
    two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to activation of MTOR and to subependymal giant cell
    tumoral     --other  
    aberrantly expressed in breast cancer cell lines and breast tumour tissues with poor prognosis and promoters are seen to be methylated in breast tumour tissues
    constitutional        
    cells lacking TSC1 have cilia that are on average 1727 p100 longer than wild-type cells, which indicates a defect in normal ciliogenesis (Hartman 2009)
    constitutional     --over  
    increased resistance to oxygen glucose deprivation (OGD) by inducing productive autophagy through an MTOR-dependent mechanism
    constitutional     --low loss of function
    loss of the TSC1 gene in the distal convoluted tubules is sufficient for renal cystogenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting TSC1/2 as a strategy for boosting antitumor immune therapy
    cancer  
    preventing the phosphorylation of TSC1 may have important clinical implications for the treatment or prevention of cancer
    cancerlung 
    selective suppression of TBC1D7 and/or inhibition of the TBC1D7-TSC1 complex formation could be promising therapeutic strategies for lung cancer therapy
    ANIMAL & CELL MODELS
  • mutations in the Drosophila Tsc1 cause a phenotype characterized by enhanced growth and increased cell size with no change in ploidy (
  • Tsc1 knockout mouse died around embryonic days 10.5-11.5, frequently associated with neural tube unclosure while Tsc1(+/-) mice developed renal and extra-renal tumors such as hepatic hemangiomas (
  • Tsc1 null embryos die at mid-gestation from a failure of liver development whereas Tsc1 heterozygotes develop kidney cystadenomas and liver hemangiomas at high frequency (
  • Mice with ventricular loss of Tsc1 had a median survival of 6 months and developed a dilated cardiomyopathy with the occurrence of scattered foci of enlarged ventricular myocytes (
  • Tsc1+/- mice show social and cognitive deficits in the absence of apparent cerebral pathology and spontaneous seizures (
  • cells with mutation in TSC1 are hypersensitive to endoplasmic reticulum stress and undergo apoptosis (