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TSC1 (Tuberous Sclerosis 1)

Identity

Other namesKIAA0234
HGNC (Hugo) TSC1
LocusID (NCBI) 7248
Location 9q34.13
Location_base_pair Starts at 135766735 and ends at 135820020 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order between D9S1199 and D9S1830
Note tumor-suppressor

DNA/RNA

Description 23 exons, of which 21 are coding; start codon is in exon 3. Different splice variants in the 5'UTR
Transcription 1 major detected transcript at 8.6 kb, 2 additional transcripts at 4 and 2.5 kb respectively; open reading frame : 3492 bp

Protein

Note called hamartin
Description 1164 amino acids, 130 kDa; C-terminal coiled-coil domain (amino acids 730 to 965)
Expression housekeeping
Localisation cytoplasmic localisation
Function binds to ezrin, member of the ERM (ezrin-moesin-radixin) actin binding proteins
Homology no strong matches with vertebrate proteins

Mutations

Germinal germline mutations cause tuberous sclerosis, known as a multiple hamartoma syndrome, autosomal dominant pattern of inheritance. Mutations are inactivating by protein truncation, no missense mutations documented. Some cases of germline mosaicism

Implicated in

Entity Tuberous Sclerosis
Note Classified as one of the phakomatosis, a group of disorders which also includes neurofibromatosis type 1 and neurofibromatosis type 2, von Hippel-Lindau disease and Sturge-Weber syndrome
Disease Growth of a variety of benign tumors (hamartomas) in multiple organs. Disease is clinically variable. Organs most frequently involved are the heart, skin, brain, lung and kidneys.
Prognosis
  • Lesions in the brain are associated with severe manifestations of TSC. Seizures occur in about 85% of the patients and they often start in the first year of life. About 50% of the children with seizures develop mental retardation. In the second and third decade of life, renal problems are found in the majority of TSC patients. Most characteristic renal abnormalities are cysts and angiomyolipomas. PROGNOSIS
  • Renal cell carcinoma develops occasionally in TSC patients.
  • Life expectancy largely depends on complications caused by the lesions in the brain and the kidneys.
  •   

    External links

    Nomenclature
    HGNC (Hugo)TSC1   12362
    Cards
    AtlasTSC1ID183
    Entrez_Gene (NCBI)TSC1  7248  tuberous sclerosis 1
    GeneCards (Weizmann)TSC1
    Ensembl (Hinxton)ENSG00000165699 [Gene_View]  chr9:135766735-135820020 [Contig_View]  TSC1 [Vega]
    AceView (NCBI)TSC1
    Genatlas (Paris)TSC1
    WikiGenes7248
    SOURCE (Princeton)NM_000368 NM_001008567 NM_001162426 NM_001162427
    Genomic and cartography
    GoldenPath (UCSC)TSC1  -  9q34.13   chr9:135766735-135820020 -  9q34   [Description]    (hg19-Feb_2009)
    EnsemblTSC1 - 9q34 [CytoView]
    Mapping of homologs : NCBITSC1 [Mapview]
    OMIM191100   605284   606690   607341   
    Gene and transcription
    Genbank (Entrez)AA215977 AB190910 AF013168 AK297326 AK299654
    RefSeq transcript (Entrez)NM_000368 NM_001008567 NM_001162426 NM_001162427
    RefSeq genomic (Entrez)AC_000141 NC_000009 NC_018920 NG_012386 NT_035014 NW_001839241 NW_004929367
    Consensus coding sequences : CCDS (NCBI)TSC1
    Cluster EST : UnigeneHs.370854 [ NCBI ]
    CGAP (NCI)Hs.370854
    Alternative Splicing : Fast-db (Paris)GSHG0031230
    Alternative Splicing GalleryENSG00000165699
    Gene ExpressionTSC1 [ NCBI-GEO ]     TSC1 [ SEEK ]   TSC1 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ92574 (Uniprot)
    NextProtQ92574  [Medical]
    With graphics : InterProQ92574
    Splice isoforms : SwissVarQ92574 (Swissvar)
    Domains : Interpro (EBI)Hamartin   
    Related proteins : CluSTrQ92574
    Domain families : Pfam (Sanger)Hamartin (PF04388)   
    Domain families : Pfam (NCBI)pfam04388   
    DMDM Disease mutations7248
    Blocks (Seattle)Q92574
    Human Protein AtlasENSG00000165699
    Peptide AtlasQ92574
    HPRD05594
    IPIIPI00022043   IPI00922188   IPI00922672   IPI00745368   IPI00936896   IPI00921907   IPI00384490   
    Protein Interaction databases
    DIP (DOE-UCLA)Q92574
    IntAct (EBI)Q92574
    FunCoupENSG00000165699
    BioGRIDTSC1
    InParanoidQ92574
    Interologous Interaction database Q92574
    IntegromeDBTSC1
    STRING (EMBL)TSC1
    Ontologies - Pathways
    Ontology : AmiGOkidney development  neural tube closure  regulation of cell-matrix adhesion  protein binding  cytoplasm  cytosol  cytosol  actin filament  cell cortex  rRNA export from nucleus  regulation of translation  potassium ion transport  cell cycle arrest  cell-matrix adhesion  negative regulation of cell proliferation  insulin receptor signaling pathway  membrane  negative regulation of translation  hippocampus development  cerebral cortex development  lamellipodium  cell projection organization  growth cone  GTPase regulator activity  negative regulation of TOR signaling cascade  GTPase activating protein binding  activation of Rho GTPase activity  response to insulin  TSC1-TSC2 complex  myelination  intracellular membrane-bounded organelle  protein complex  regulation of phosphoprotein phosphatase activity  negative regulation of cell size  regulation of protein kinase activity  protein N-terminus binding  synapse organization  protein stabilization  chaperone binding  protein heterooligomerization  regulation of stress fiber assembly  positive regulation of focal adhesion assembly  cardiac muscle cell differentiation  
    Ontology : EGO-EBIkidney development  neural tube closure  regulation of cell-matrix adhesion  protein binding  cytoplasm  cytosol  cytosol  actin filament  cell cortex  rRNA export from nucleus  regulation of translation  potassium ion transport  cell cycle arrest  cell-matrix adhesion  negative regulation of cell proliferation  insulin receptor signaling pathway  membrane  negative regulation of translation  hippocampus development  cerebral cortex development  lamellipodium  cell projection organization  growth cone  GTPase regulator activity  negative regulation of TOR signaling cascade  GTPase activating protein binding  activation of Rho GTPase activity  response to insulin  TSC1-TSC2 complex  myelination  intracellular membrane-bounded organelle  protein complex  regulation of phosphoprotein phosphatase activity  negative regulation of cell size  regulation of protein kinase activity  protein N-terminus binding  synapse organization  protein stabilization  chaperone binding  protein heterooligomerization  regulation of stress fiber assembly  positive regulation of focal adhesion assembly  cardiac muscle cell differentiation  
    Pathways : BIOCARTAmTOR Signaling Pathway [Genes]   
    Pathways : KEGGmTOR signaling pathway    PI3K-Akt signaling pathway    Insulin signaling pathway   
    REACTOMETSC1
    Protein Interaction DatabaseTSC1
    Wikipedia pathwaysTSC1
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)TSC1
    SNP (GeneSNP Utah)TSC1
    SNP : HGBaseTSC1
    Genetic variants : HAPMAPTSC1
    1000_GenomesTSC1 
    ICGC programENSG00000165699 
    Cancer Gene: CensusTSC1 
    Somatic Mutations in Cancer : COSMICTSC1 
    CONAN: Copy Number AnalysisTSC1 
    Mutations and Diseases : HGMDTSC1
    OMIM191100    605284    606690    607341   
    GENETestsTSC1
    Disease Genetic AssociationTSC1
    Huge Navigator TSC1 [HugePedia]  TSC1 [HugeCancerGEM]
    Genomic VariantsTSC1  TSC1 [DGVbeta]
    Exome VariantTSC1
    dbVarTSC1
    ClinVarTSC1
    snp3D : Map Gene to Disease7248
    General knowledge
    Homologs : HomoloGeneTSC1
    Homology/Alignments : Family Browser (UCSC)TSC1
    Phylogenetic Trees/Animal Genes : TreeFamTSC1
    Chemical/Protein Interactions : CTD7248
    Chemical/Pharm GKB GenePA37034
    Drug Sensitivity TSC1
    Clinical trialTSC1
    Cancer Resource (Charite)ENSG00000165699
    Other databases
    Probes
    Litterature
    PubMed157 Pubmed reference(s) in Entrez
    CoreMineTSC1
    iHOPTSC1

    Bibliography

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    Science (New York, N.Y.). 1997 ; 277 (5327) : 805-808.
    PMID 9242607
     
    Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.
    van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P
    Human molecular genetics. 1998 ; 7 (6) : 1053-1057.
    PMID 9580671
     
    Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.
    Plank TL, Yeung RS, Henske EP
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    PMID 9809973
     
    Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.
    van Slegtenhorst M, Verhoef S, Tempelaars A, Bakker L, Wang Q, Wessels M, Bakker R, Nellist M, Lindhout D, Halley D, van den Ouweland A
    Journal of medical genetics. 1999 ; 36 (4) : 285-289.
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    Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.
    Jones AC, Shyamsundar MM, Thomas MW, Maynard J, Idziaszczyk S, Tomkins S, Sampson JR, Cheadle JP
    American journal of human genetics. 1999 ; 64 (5) : 1305-1315.
    PMID 10205261
     
    Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin.
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    The Journal of biological chemistry. 1999 ; 274 (50) : 35647-35652.
    PMID 10585443
     
    The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1- and TSC2-linked angiomyolipomas.
    Plank TL, Logginidou H, Klein-Szanto A, Henske EP
    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 1999 ; 12 (5) : 539-545.
    PMID 10349994
     
    The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination.
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    Oncogene. 2000 ; 19 (54) : 6306-6316.
    PMID 11175345
     
    Genomic organization and comparative analysis of the mouse tuberous sclerosis 1 (Tsc1) locus.
    Cheadle JP, Dobbie L, Idziaszczyk S, Hodges AK, Smith AJ, Sampson JR, Young J
    Mammalian genome : official journal of the International Mammalian Genome Society. 2000 ; 11 (12) : 1135-1138.
    PMID 11130985
     
    The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho.
    Lamb RF, Roy C, Diefenbach TJ, Vinters HV, Johnson MW, Jay DG, Hall A
    Nature cell biology. 2000 ; 2 (5) : 281-287.
    PMID 10806479
     
    The TSC1 gene product, hamartin, negatively regulates cell proliferation.
    Miloloza A, Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschlˆ§ger M
    Human molecular genetics. 2000 ; 9 (12) : 1721-1727.
    PMID 10915759
     
    Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.
    Hendy GN, D'Souza-Li L, Yang B, Canaff L, Cole DE
    Human mutation. 2000 ; 16 (4) : 281-296.
    PMID 11013439
     
    Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis.
    Aicher LD, Campbell JS, Yeung RS
    The Journal of biological chemistry. 2001 ; 276 (24) : 21017-21021.
    PMID 11290735
     
    Hamartin expression and interaction with tuberin in tumor cell lines and primary cultures.
    Catania MG, Johnson MW, Liau LM, Kremen TJ, deVellis JS, Vinters HV
    Journal of neuroscience research. 2001 ; 63 (3) : 276-283.
    PMID 11170177
     
    Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B.
    Catania MG, Mischel PS, Vinters HV
    Journal of neuropathology and experimental neurology. 2001 ; 60 (7) : 711-723.
    PMID 11444800
     
    Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.
    Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ
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    PMID 11112665
     
    A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice.
    Kobayashi T, Minowa O, Sugitani Y, Takai S, Mitani H, Kobayashi E, Noda T, Hino O
    Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (15) : 8762-8767.
    PMID 11438694
     
    Hamartin and tuberin expression in human tissues.
    Johnson MW, Kerfoot C, Bushnell T, Li M, Vinters HV
    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2001 ; 14 (3) : 202-210.
    PMID 11266527
     
    Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.
    Potter CJ, Huang H, Xu T
    Cell. 2001 ; 105 (3) : 357-368.
    PMID 11348592
     
    The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.
    Tapon N, Ito N, Dickson BJ, Treisman JE, Hariharan IK
    Cell. 2001 ; 105 (3) : 345-355.
    PMID 11348591
     
    REVIEW articlesautomatic search in PubMed
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    Contributor(s)

    Written11-2001Marjon van Slegtenhorst and Elizabeth Petri Henske
    Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia PA 19111, USA

    Citation

    This paper should be referenced as such :
    van Slegtenhorst M, Petri Henske E . TSC1 (Tuberous Sclerosis 1). Atlas Genet Cytogenet Oncol Haematol. November 2001 .
    URL : http://AtlasGeneticsOncology.org/Genes/TSC1ID183.html

    The various updated versions of this paper are referenced and archived by INIST as such :
    http://documents.irevues.inist.fr/bitstream/2042/37811/1/11-2001-TSC1ID183.pdf   [ Bibliographic record ]

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Apr 18 17:20:24 CEST 2014

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