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TSC2 (tuberous sclerosis 2)

Written2001-11Aristotelis Astrinidis, Elizabeth Petri Henske
Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia PA 19111, USA

(Note : for Links provided by Atlas : click)

Identity

HGNC (Hugo) TSC2
LocusID (NCBI) 7249
Atlas_Id 184
Location 16p13.3  [Link to chromosome band 16p13]
Location_base_pair Starts at 2097896 and ends at 2138721 bp from pter ( according to hg19-Feb_2009)  [Mapping TSC2.png]
Fusion genes
(updated 2016)
TSC2 (16p13.3) / CASKIN1 (16p13.3)TSC2 (16p13.3) / CHTF18 (16p13.3)TSC2 (16p13.3) / RPS2 (16p13.3)
TSC2 (16p13.3) / SYNGR3 (16p13.3)TSC2 (16p13.3) / TMEM204 (16p13.3)TSC2 (16p13.3) / TSC2 (16p13.3)

DNA/RNA

Description 41 exons; spans 41kb
Transcription At least 3 alternate splicings; 5.5kb mRNA complete cds; coding sequence: CDS 19-5442

Protein

Description Tuberin; 1807 amino acids; 190 kDaltons
Expression Expressed in most embryonic and adult tissues
Localisation Cytoplasmic
Function Potential GTPase activating protein (GAP) for Rap1a and/or Rab5; Interacts with hamartin ( TSC1 gene product) and Rabaptin-5
Homology 188 residues at the COOH terminus have homology to Rap/Ran GAP

Mutations

Germinal Large genomic deletions in <10% of cases; point mutations widely dispersed, with no cluster; truncating effect in 2/3 of cases
Somatic loss-of-heterozygosity in 2/3 of renal angiomyolipomas; Somatic mutations in angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM) cells from women with sporadic LAM

Implicated in

Note
Entity Tuberous Sclerosis Comples (TSC)
Disease Autosomal dominant disease characterized by seizures, mental retardation, autism, benign tumors of the brain, heart, skin, kidney, and malignant kidney tumors.
  
Entity Sporadic lymphangioleiomyomatosis (LAM)
Disease Lung disease affecting almost exclusively women, characterized by diffuse bilateral proliferation of abnormal smooth muscle cells in the lungs
  

Bibliography

Identification and characterization of the tuberous sclerosis gene on chromosome 16.
European Chromosome 16 Tuberous Sclerosis Consortium, European Chromosome 16 Tuberous Sclerosis Consortium
Cell. 1993 ; 75 (7) : 1305-1315.
PMID 8269512
 
9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene.
Carbonara C, Longa L, Grosso E, Borrone C, Garrè MG, Brisigotti M, Migone N
Human molecular genetics. 1994 ; 3 (10) : 1829-1832.
PMID 7849708
 
Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients.
Green AJ, Smith M, Yates JR
Nature genetics. 1994 ; 6 (2) : 193-196.
PMID 8162074
 
Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas.
Henske EP, Neumann HP, Scheithauer BW, Herbst EW, Short MP, Kwiatkowski DJ
Genes, chromosomes & cancer. 1995 ; 13 (4) : 295-298.
PMID 7547639
 
Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity.
Wienecke R, König A, DeClue JE
The Journal of biological chemistry. 1995 ; 270 (27) : 16409-16414.
PMID 7608212
 
Role of the tuberous sclerosis gene-2 product in cell cycle control. Loss of the tuberous sclerosis gene-2 induces quiescent cells to enter S phase.
Soucek T, Pusch O, Wienecke R, DeClue JE, Hengstschlä M
The Journal of biological chemistry. 1997 ; 272 (46) : 29301-29308.
PMID 9361010
 
The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis.
Xiao GH, Shoarinejad F, Jin F, Golemis EA, Yeung RS
The Journal of biological chemistry. 1997 ; 272 (10) : 6097-6100.
PMID 9045618
 
Tuberous sclerosis gene 2 product modulates transcription mediated by steroid hormone receptor family members.
Henry KW, Yuan X, Koszewski NJ, Onda H, Kwiatkowski DJ, Noonan DJ
The Journal of biological chemistry. 1998 ; 273 (32) : 20535-20539.
PMID 9685410
 
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
Cancer research. 1998 ; 58 (21) : 4766-4770.
PMID 9809973
 
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
 
gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle.
Ito N, Rubin GM
Cell. 1999 ; 96 (4) : 529-539.
PMID 10052455
 
Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice.
Kobayashi T, Minowa O, Kuno J, Mitani H, Hino O, Noda T
Cancer research. 1999 ; 59 (6) : 1206-1211.
PMID 10096549
 
Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background.
Onda H, Lueck A, Marks PW, Warren HB, Kwiatkowski DJ
The Journal of clinical investigation. 1999 ; 104 (6) : 687-695.
PMID 10491404
 
Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.
Carsillo T, Astrinidis A, Henske EP
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (11) : 6085-6090.
PMID 10823953
 
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
 

Citation

This paper should be referenced as such :
Astrinidis, A ; Petri, Henske E
TSC2 (tuberous sclerosis 2)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(1):27-28.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TSC2ID184.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
  Lymphangioleiomyomatosis
Soft Tissues: Lymphangioleiomyoma
Pancreatic tumors: an overview
Kidney: Renal cell carcinoma
Soft tissue tumors: an overview

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
  Familial nervous system tumour syndromes Tuberous sclerosis (TSC)

External links

Nomenclature
HGNC (Hugo)TSC2   12363
Cards
AtlasTSC2ID184
Entrez_Gene (NCBI)TSC2  7249  tuberous sclerosis 2
AliasesLAM; PPP1R160; TSC4
GeneCards (Weizmann)TSC2
Ensembl hg19 (Hinxton)ENSG00000103197 [Gene_View]  chr16:2097896-2138721 [Contig_View]  TSC2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000103197 [Gene_View]  chr16:2097896-2138721 [Contig_View]  TSC2 [Vega]
ICGC DataPortalENSG00000103197
TCGA cBioPortalTSC2
AceView (NCBI)TSC2
Genatlas (Paris)TSC2
WikiGenes7249
SOURCE (Princeton)TSC2
Genomic and cartography
GoldenPath hg19 (UCSC)TSC2  -     chr16:2097896-2138721 +  16p13.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TSC2  -     16p13.3   [Description]    (hg38-Dec_2013)
EnsemblTSC2 - 16p13.3 [CytoView hg19]  TSC2 - 16p13.3 [CytoView hg38]
Mapping of homologs : NCBITSC2 [Mapview hg19]  TSC2 [Mapview hg38]
OMIM191092   606690   613254   
Gene and transcription
Genbank (Entrez)AB210000 AK022401 AK094152 AK125096 AK294548
RefSeq transcript (Entrez)NM_000548 NM_001077183 NM_001114382 NM_001318827 NM_001318829 NM_001318831 NM_001318832 NM_021055 NM_021056
RefSeq genomic (Entrez)NC_000016 NC_018927 NG_005895 NT_010393 NW_004929400
Consensus coding sequences : CCDS (NCBI)TSC2
Cluster EST : UnigeneHs.90303 [ NCBI ]
CGAP (NCI)Hs.90303
Alternative Splicing GalleryENSG00000103197
Gene ExpressionTSC2 [ NCBI-GEO ]   TSC2 [ EBI - ARRAY_EXPRESS ]   TSC2 [ SEEK ]   TSC2 [ MEM ]
Gene Expression Viewer (FireBrowse)TSC2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7249
GTEX Portal (Tissue expression)TSC2
Protein : pattern, domain, 3D structure
UniProt/SwissProtP49815 (Uniprot)
NextProtP49815  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP49815
Splice isoforms : SwissVarP49815 (Swissvar)
PhosPhoSitePlusP49815
Domaine pattern : Prosite (Expaxy)RAPGAP (PS50085)   
Domains : Interpro (EBI)ARM-like    ARM-type_fold    Rap_GAP_dom    Tuberin    Tuberin-type_domain    Tuberin_N   
Domain families : Pfam (Sanger)DUF3384 (PF11864)    Rap_GAP (PF02145)    Tuberin (PF03542)   
Domain families : Pfam (NCBI)pfam11864    pfam02145    pfam03542   
DMDM Disease mutations7249
Blocks (Seattle)TSC2
SuperfamilyP49815
Human Protein AtlasENSG00000103197
Peptide AtlasP49815
HPRD01850
IPIIPI00028493   IPI00218881   IPI00952929   IPI00218883   IPI00954095   IPI00552156   IPI00879496   IPI00877641   IPI00877797   
Protein Interaction databases
DIP (DOE-UCLA)P49815
IntAct (EBI)P49815
FunCoupENSG00000103197
BioGRIDTSC2
STRING (EMBL)TSC2
ZODIACTSC2
Ontologies - Pathways
QuickGOP49815
Ontology : AmiGOneural tube closure  GTPase activator activity  protein binding  nucleus  nucleus  cytoplasm  cytoplasm  lysosome  Golgi apparatus  Golgi apparatus  cytosol  cytosol  negative regulation of protein kinase activity  protein import into nucleus  endocytosis  cell cycle arrest  heart development  protein localization  negative regulation of cell proliferation  negative regulation of phosphatidylinositol 3-kinase signaling  membrane  viral process  vesicle-mediated transport  phosphatase binding  regulation of endocytosis  negative regulation of Wnt signaling pathway  small GTPase binding  negative regulation of TOR signaling  TSC1-TSC2 complex  protein homodimerization activity  protein kinase B signaling  positive regulation of GTPase activity  regulation of insulin receptor signaling pathway  negative regulation of insulin receptor signaling pathway  insulin-like growth factor receptor signaling pathway  perinuclear region of cytoplasm  positive chemotaxis  regulation of small GTPase mediated signal transduction  regulation of cell cycle  negative regulation of protein kinase B signaling  negative regulation of protein kinase B signaling  
Ontology : EGO-EBIneural tube closure  GTPase activator activity  protein binding  nucleus  nucleus  cytoplasm  cytoplasm  lysosome  Golgi apparatus  Golgi apparatus  cytosol  cytosol  negative regulation of protein kinase activity  protein import into nucleus  endocytosis  cell cycle arrest  heart development  protein localization  negative regulation of cell proliferation  negative regulation of phosphatidylinositol 3-kinase signaling  membrane  viral process  vesicle-mediated transport  phosphatase binding  regulation of endocytosis  negative regulation of Wnt signaling pathway  small GTPase binding  negative regulation of TOR signaling  TSC1-TSC2 complex  protein homodimerization activity  protein kinase B signaling  positive regulation of GTPase activity  regulation of insulin receptor signaling pathway  negative regulation of insulin receptor signaling pathway  insulin-like growth factor receptor signaling pathway  perinuclear region of cytoplasm  positive chemotaxis  regulation of small GTPase mediated signal transduction  regulation of cell cycle  negative regulation of protein kinase B signaling  negative regulation of protein kinase B signaling  
Pathways : BIOCARTAControl of Gene Expression by Vitamin D Receptor [Genes]    mTOR Signaling Pathway [Genes]   
Pathways : KEGGp53 signaling pathway    mTOR signaling pathway    PI3K-Akt signaling pathway    Insulin signaling pathway    Thyroid hormone signaling pathway   
REACTOMEP49815 [protein]
REACTOME PathwaysR-HSA-5628897 TP53 Regulates Metabolic Genes [pathway]
REACTOME PathwaysR-HSA-165181 Inhibition of TSC complex formation by PKB [pathway]
REACTOME PathwaysR-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer [pathway]
REACTOME PathwaysR-HSA-1632852 Macroautophagy [pathway]
REACTOME PathwaysR-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK [pathway]
REACTOME PathwaysR-HSA-198323 AKT phosphorylates targets in the cytosol [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkTSC2
Wikipedia pathwaysTSC2
Orthology - Evolution
OrthoDB7249
GeneTree (enSembl)ENSG00000103197
Phylogenetic Trees/Animal Genes : TreeFamTSC2
Homologs : HomoloGeneTSC2
Homology/Alignments : Family Browser (UCSC)TSC2
Gene fusions - Rearrangements
Fusion : MitelmanTSC2/TMEM204 [16p13.3/16p13.3]  
Fusion: TCGATSC2 16p13.3 TMEM204 16p13.3 BRCA
Polymorphisms : SNP, variants
NCBI Variation ViewerTSC2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TSC2
dbVarTSC2
ClinVarTSC2
1000_GenomesTSC2 
Exome Variant ServerTSC2
ExAC (Exome Aggregation Consortium)TSC2 (select the gene name)
Genetic variants : HAPMAP7249
Genomic Variants (DGV)TSC2 [DGVbeta]
Mutations
ICGC Data PortalTSC2 
TCGA Data PortalTSC2 
Broad Tumor PortalTSC2
OASIS PortalTSC2 [ Somatic mutations - Copy number]
Cancer Gene: CensusTSC2 
Somatic Mutations in Cancer : COSMICTSC2 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Tuberous sclerosis database
BioMutasearch TSC2
DgiDB (Drug Gene Interaction Database)TSC2
DoCM (Curated mutations)TSC2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TSC2 (select a term)
intoGenTSC2
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)16:2097896-2138721  ENSG00000103197
CONAN: Copy Number AnalysisTSC2 
Mutations and Diseases : HGMDTSC2
OMIM191092    606690    613254   
MedgenTSC2
Genetic Testing Registry TSC2
NextProtP49815 [Medical]
TSGene7249
GENETestsTSC2
Huge Navigator TSC2 [HugePedia]
snp3D : Map Gene to Disease7249
BioCentury BCIQTSC2
ClinGenTSC2 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7249
Chemical/Pharm GKB GenePA37035
Clinical trialTSC2
Miscellaneous
canSAR (ICR)TSC2 (select the gene name)
Other databasehttp://zk.bwh.harvard.edu/ts/TSC2-19.htm
Probes
Litterature
PubMed311 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTSC2
EVEXTSC2
GoPubMedTSC2
iHOPTSC2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Sat Jun 11 13:00:32 CEST 2016

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