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TSC2 Gene

protein-coding   GIFtS: 71
GCID: GC16P002097

Tuberous Sclerosis 2


(Previous symbol: TSC4)
  See TSC2-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Tuberous Sclerosis 21 2
TSC41 2 3
Tuberous Sclerosis 2 Protein2 3
LAM2 5
tuberin2

External Ids:    HGNC: 123631   Entrez Gene: 72492   Ensembl: ENSG000001031977   OMIM: 1910925   UniProtKB: P498153   

Export aliases for TSC2 gene to outside databases

Previous GC identifers: GC16P002115 GC16P002038 GC16P002037


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TSC2 Gene:
Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor
and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly
acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding
different isoforms. (provided by RefSeq, Jul 2008)

GeneCards Summary for TSC2 Gene:
TSC2 (tuberous sclerosis 2) is a protein-coding gene. Diseases associated with TSC2 include subependymoma, and tuberous sclerosis, type 2. GO annotations related to this gene include GTPase activator activity and protein homodimerization activity. An important paralog of this gene is RALGAPA2.

UniProtKB/Swiss-Prot: TSC2_HUMAN, P49815
Function: In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1
and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small
GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. Implicated as a tumor suppressor.
Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling.
Stimulates weakly the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 in vitro. Mutations in
TSC2 lead to constitutive activation of RAP1A in tumors

Gene Wiki entry for TSC2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000016.9  NT_010393.17  NC_018927.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TSC2 gene promoter:
         NF-1   STAT3   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): TSC2 promoter sequence
   Search Chromatin IP Primers for TSC2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TSC2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 16p13.3   Ensembl cytogenetic band:  16p13.3   HGNC cytogenetic band: 16p13.3

TSC2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TSC2 gene location

GeneLoc information about chromosome 16         GeneLoc Exon Structure

GeneLoc location for GC16P002097:  view genomic region     (about GC identifiers)

Start:
2,097,466 bp from pter      End:
2,138,716 bp from pter
Size:
41,251 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: TSC2_HUMAN, P49815 (See protein sequence)
Recommended Name: Tuberin  
Size: 1807 amino acids; 200608 Da
Subunit: Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction
with HERC1. May also interact with the adapter molecule RABEP1. The final complex contains TSC2 and RABEP1 linked
to RAB5 (Probable). Interacts with HSPA1 and HSPA8. Interacts with DAPK1 and FBXW5
Sequence caution: Sequence=BAE06082.1; Type=Erroneous initiation;
Secondary accessions: A7E2E2 B4DIQ7 B4DRN2 C9J378 O75275 Q4LE71 Q8TAZ1
Alternative splicing: 6 isoforms:  P49815-1   P49815-2   P49815-3   P49815-4   P49815-5   P49815-6   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for TSC2: NX_P49815

Explore proteomics data for TSC2 at MOPED

Post-translational modifications: 

  • Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1. Phosphorylation at
    Ser-939 and Thr-1462 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it
    and leads to negatively regulates the mTORC1 complex. Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation
    inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK11
  • Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation1
  • Ubiquitination2 at Lys34, Lys72, Lys438, Lys634, Lys658, Lys914, Lys930, Lys1251, Lys1701, Lys1739
  • Modification sites at PhosphoSitePlus

  • See TSC2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_000539.2  NP_001070651.1  NP_001107854.1  

    ENSEMBL proteins: 
     ENSP00000219476   ENSP00000371978   ENSP00000384468   ENSP00000399232   ENSP00000344383  
     ENSP00000406980   ENSP00000454487   ENSP00000387937   ENSP00000454997   ENSP00000455997  
     ENSP00000460310   ENSP00000458541   ENSP00000455817   ENSP00000248099  
    Reactome Protein details: P49815

    TSC2 Human Recombinant Protein Products:

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    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for TSC2

     
    Search eBioscience for Proteins for TSC2 

     
    antibodies-online proteins for TSC2 (2 products) 

     
    antibodies-online peptides for TSC2

    TSC2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TSC2
    R&D Systems Antibodies for TSC2
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    antibodies-online antibodies for TSC2 (487 products) 

    TSC2 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript Custom Assay Services for TSC2
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for TSC2
    Cloud-Clone Corp. CLIAs for TSC2
    Search eBioscience for ELISAs for TSC2 
    antibodies-online kits for TSC2 (4 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 7):
     IPR027107 Tuberin/Ral-act_asu
     IPR011989 ARM-like
     IPR018515 Tuberin-type_domain
     IPR003913 Tuberin
     IPR000331 Rap_GAP_dom

    Graphical View of Domain Structure for InterPro Entry P49815

    ProtoNet protein and cluster: P49815

    2 Blocks protein domains:
    IPB000331 Rap/ran-GAP
    IPB003913 Tuberin signature


    UniProtKB/Swiss-Prot: TSC2_HUMAN, P49815
    Similarity: Contains 1 Rap-GAP domain


    Find genes that share domains with TSC2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TSC2_HUMAN, P49815
    Function: In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1
    and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small
    GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. Implicated as a tumor suppressor.
    Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling.
    Stimulates weakly the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 in vitro. Mutations in
    TSC2 lead to constitutive activation of RAP1A in tumors

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005096GTPase activator activity IDA9045618
    GO:0005488binding ----
    GO:0005515protein binding IPI10585443
    GO:0019902phosphatase binding IDA19389623
    GO:0042803protein homodimerization activity IPI10585443
         
    Find genes that share ontologies with TSC2           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for TSC2:
     Upregulation of Wnt/beta-caten 

         Selected MGI mutant phenotypes (inferred from 12 alleles(MGI details for Tsc2) (see all 16):
     behavior/neurological  cardiovascular system  cellular  embryogenesis  endocrine/exocrine gland 
     growth/size/body  hematopoietic system  homeostasis/metabolism  integument  liver/biliary system 
     mortality/aging  nervous system  normal  renal/urinary system  reproductive system 

    Find genes that share phenotypes with TSC2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for TSC2: Tsc2tm1Djk Tsc2tm1.2Mjg Tsc2tm1.1Kido Tsc2tm1Jusa

       genOway: Develop your customized and physiologically relevant rodent model for TSC2

    miRNA
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    miRTarBase miRNAs that target TSC2:
    hsa-mir-744-5p (MIRT037646), hsa-mir-17-5p (MIRT050917), hsa-mir-296-3p (MIRT038502)

    Block miRNA regulation of human, mouse, rat TSC2 using miScript Target Protectors
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    Predesigned siRNA for gene silencing in human, mouse, rat TSC2

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 3): TSC2 (NM_004089)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TSC2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TSC2
    Addgene plasmids for TSC2 

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    Flow Cytometry
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    eBioscience FlowRNA Probe Sets ( VA1-12340) for TSC2 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TSC2_HUMAN, P49815: Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association
    with membranes
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol5
    golgi apparatus5
    nucleus5
    plasma membrane3
    cytoskeleton2
    endosome1
    vacuole1

    Gene Ontology (GO): Selected cellular component terms (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634NOT nucleus IDA16636147
    GO:0005737colocalizes with cytoplasm IDA17114346
    GO:0005794NOT Golgi apparatus IDA10585443
    GO:0005829cytosol TAS--
    GO:0005901caveola IEA--

    Find genes that share ontologies with TSC2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TSC2 About   (see all 42)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Development IGF 1 receptor signaling
    Development IGF RI signaling0.49
    Development IGF 1 receptor signaling0.48
    Signal transduction AKT signaling0.49
    2Insulin receptor signalling cascade
    Insulin receptor signalling cascade0.94
    Signaling by Insulin receptor0.80
    IRS-related events0.94
    PKB-mediated events0.41
    Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)0.92
    mTOR signalling0.39
    IRS-mediated signalling0.92
    TOR signaling0.32
    3Translation Insulin regulation of translation
    Translation Insulin regulation of translation0.59
    Development CNTF receptor signaling0.43
    Regulation of lipid metabolism Insulin signaling generic cascades0.59
    Development Growth hormone signaling via PI3K AKT and MAPK cascades0.34
    Transcription Receptor mediated HIF regulation0.51
    mTOR signaling pathway0.34
    Translation Regulation activity of EIF4F0.44
    Insulin signaling pathway0.32
    4PI-3K cascade
    PI3K/AKT activation0.93
    PI3K events in ERBB4 signaling0.88
    GAB1 signalosome0.93
    Role of LAT2/NTAL/LAB on calcium mobilization0.80
    Constitutive PI3K/AKT Signaling in Cancer0.88
    Signaling by SCF-KIT0.72
    PIP3 activates AKT signaling0.88
    Signaling by ERBB40.66
    5Signaling by FGFR
    Signaling by FGFR0.91
    DAP12 interactions0.89
    Signaling by FGFR in disease0.91
    Signaling by PDGF0.87
    Downstream signaling of activated FGFR0.91
    Signaling by EGFR0.83
    Downstream signal transduction0.90
    Signaling by EGFR in Cancer0.82


    Find genes that share SuperPaths with TSC2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for TSC2
        Akt Signaling Pathway

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TSC2 (see all 6)
        AMPK Enzyme Complex Pathway
    Molecular Mechanisms of Cancer
    Glioblastoma Multiforme
    mTOR Pathway
    14-3-3 Induced Intracellular Signaling

    3 Cell Signaling Technology (CST) Pathways for TSC2
        Translational Control
    PI3K / Akt Signaling
    Glucose / Energy Metabolism

    Selected GeneGo (Thomson Reuters) Pathways for TSC2 (see all 15)
        Development Endothelin-1/EDNRA transactivation of EGFR
    Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
    Development CNTF receptor signaling
    Signal transduction AKT signaling
    Signal transduction PTEN pathway

    Selected BioSystems Pathways for TSC2 (see all 14)
        TOR signaling
    Insulin Signaling
    AMPK signaling
    Integrated Breast Cancer Pathway
    BDNF signaling pathway

    4 Reactome Pathways for TSC2
        AKT phosphorylates targets in the cytosol
    Regulation of Rheb GTPase activity by AMPK
    Constitutive PI3K/AKT Signaling in Cancer
    Inhibition of TSC complex formation by PKB


    5 Kegg Pathways  (Kegg details for TSC2):
        p53 signaling pathway
    mTOR signaling pathway
    PI3K-Akt signaling pathway
    Insulin signaling pathway
    Thyroid hormone signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TSC2: 
              mTOR Signaling in human mouse rat
              Primary Cilia in human mouse rat
              PI3K-AKT Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TSC2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TSC2 (P498151, 2, 3 ENSP000002194764) via UniProtKB, MINT, STRING, and/or I2D (see all 238)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    YWHAZP631041, 2, 3, ENSP000003095034EBI-396587,EBI-347088 MINT-16861 MINT-3294932 MINT-7899812 MINT-3294490 MINT-8006126 MINT-16860 MINT-8009615 MINT-8009622 MINT-15413 MINT-3317863 I2D: score=6 STRING: ENSP00000309503
    YWHABP319461, 2, 3, ENSP000003001614EBI-396587,EBI-359815 MINT-15978 MINT-50944 MINT-8006321 MINT-8009815 MINT-8006263 MINT-15979 MINT-17162 MINT-15977 I2D: score=6 STRING: ENSP00000300161
    ENSG00000212866P081073I2D: score=1 
    ENSG00000215328P081073I2D: score=1 
    ENSG00000224501P081073I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 39):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IEA--
    GO:0001843neural tube closure ISS--
    GO:0006469negative regulation of protein kinase activity ISS--
    GO:0006606protein import into nucleus ISS--
    GO:0006897endocytosis TAS9045618

    Find genes that share ontologies with TSC2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for TSC2

    Selected Novoseek inferred chemical compound relationships for TSC2 gene (see all 25)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    rapamycin 89.6 117 19539245 (3), 12957289 (3), 17043358 (2), 18650261 (2) (see all 74)
    wortmannin 50.8 6 12867426 (1), 15626752 (1), 16053916 (1), 15579767 (1) (see all 5)
    phosphatidylinositol 42.4 10 12167664 (2), 12438239 (2), 14982927 (1), 16459993 (1) (see all 7)
    phosphoinositide 37.8 6 12867426 (2), 19143635 (1), 12773160 (1), 16231158 (1) (see all 5)
    ly294002 33 3 12167664 (1), 16150885 (1), 15579767 (1)
    threonine 20.1 3 17458623 (1), 18555664 (1), 14993219 (1)
    gtp 15.6 9 19176517 (2), 15772076 (2), 15340059 (1), 14729330 (1) (see all 6)
    serine 12.2 6 11290735 (2), 17458623 (1), 14993219 (1), 18555664 (1)
    okadaic acid 11.9 5 16150885 (3), 19070673 (1)
    estrogen 8.23 18 17114346 (3), 12581886 (2), 15039427 (2), 12700139 (2) (see all 7)

    1 PharmGKB related drug/compound annotation for TSC2 gene    About this table
    Drug/compound PharmGKB Annotation
    everolimus



    Find genes that share compounds with TSC2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TSC2 gene (5 alternative transcripts): 
    NM_000548.3  NM_001077183.1  NM_001114382.1  NM_021055.1  NM_021056.1  

    Unigene Cluster for TSC2:

    Tuberous sclerosis 2
    Hs.90303  [show with all ESTs]
    Unigene Representative Sequence: NM_000548
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 27):
    ENST00000219476(uc002con.3 uc010bsd.3 uc002coo.3 uc010uvv.2 uc010uvw.2 uc002cop.3)
    ENST00000382538 ENST00000401874 ENST00000461648(uc010uvu.1) ENST00000439673
    ENST00000350773 ENST00000439117 ENST00000568454 ENST00000432909 ENST00000568692
    ENST00000467949 ENST00000463601 ENST00000568566 ENST00000490108 ENST00000568238
    ENST00000488675 ENST00000562474 ENST00000563346
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    Additional mRNA sequence: 

    AB210000.1 AK094152.1 AK125096.1 AK294548.1 AK295672.1 AK295728.1 AK299343.1 BC025364.1 
    BC046929.1 BC150300.1 BX647816.1 X75621.1 

    Selected DOTS entries (see all 30):

    DT.120674930  DT.100037834  DT.447378  DT.100820455  DT.95360119  DT.101973887  DT.100721251  DT.100775042 
    DT.95199164  DT.70104277  DT.91644432  DT.86844536  DT.100820454  DT.120674892  DT.91901331  DT.97760273 
    DT.100000256  DT.120674936  DT.120675020  DT.91853013  DT.120674882  DT.120674961  DT.120674991  DT.120675024 

    Selected AceView cDNA sequences (see all 309):

    AI962215 NM_021056 BI856165 BG818177 BC046929 BQ054623 BM925150 BU738647 
    CO248095 BQ066412 BM987875 BC025364 CD675300 BF724869 BU168143 AW950530 
    CA392462 CF135856 BQ062032 CR601803 BQ434112 BM790197 BM981801 BQ025541 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for TSC2 (see all 18)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16a · 16b ^ 17a · 17b · 17c · 17d ^ 18 ^ 19 ^
    SP1:        -                       -                                                                 -           -           -                                 
    SP2:                                                                                                                                                            
    SP3:                                                                                                                                                            
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                            

    ExUns: 20a · 20b ^ 21 ^ 22a · 22b ^ 23a · 23b ^ 24 ^ 25a · 25b · 25c · 25d ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29a · 29b · 29c ^ 30a · 30b · 30c ^ 31 ^ 32 ^ 33a ·
    SP1:                                                                    -           -     -     -                                                               
    SP2:                                                                                                                                                            
    SP3:                                                                    -           -     -     -                                                               
    SP4:                                                                    -                                                                                       
    SP5:                                                                    -           -     -     -                                                               

    ExUns: 33b ^ 34a · 34b ^ 35a · 35b ^ 36 ^ 37a · 37b · 37c ^ 38 ^ 39 ^ 40 ^ 41 ^ 42 ^ 43 ^ 44 ^ 45a · 45b
    SP1:        -     -     -     -                                                                                 
    SP2:                                                                                                            
    SP3:                                                                                                            
    SP4:                                                                                                            
    SP5:                                                                                                            


    ECgene alternative splicing isoforms for TSC2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    TSC2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GAGGGCCTTG
    TSC2 Expression
    About this image

    TSC2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TSC2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.90303

    UniProtKB/Swiss-Prot: TSC2_HUMAN, P49815
    Tissue specificity: Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle,
    kidney, lung and placenta

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TSC2: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for TSC2 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tsc21 , 5 tuberous sclerosis 21, 5 84.86(n)1
    91.65(a)1
      17 (12.41 cM)5
    220841  NM_001039363.21  NP_001034452.11 
     245959375 
    chicken
    (Gallus gallus)
    Aves TSC21 tuberous sclerosis 2 74.88(n)
    82.33(a)
      416552  XM_003642120.2  XP_003642168.2 
    lizard
    (Anolis carolinensis)
    Reptilia TSC26
    tuberous sclerosis 2
    81(a)
    1 ↔ 1
    GL344117.1(42293-94216)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.75022 Xenopus laevis transcribed sequence with weak similarity more 74.25(n)    48029715 
    zebrafish
    (Danio rerio)
    Actinopterygii CD014673.12   -- 74.03(n)    CD014673.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta gig1 , 3 negative regulation of cell size3
    gigas1
    31(a)3
    49.52(n)1
    37.89(a)1
      3 76F23
    402011  NM_079453.31  NP_524177.11 


    ENSEMBL Gene Tree for TSC2 (if available)
    TreeFam Gene Tree for TSC2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TSC2 gene
    RALGAPA22  RALGAPA12  
    2 SIMAP similar genes for TSC2 using alignment to 9 protein entries:     TSC2_HUMAN (see all proteins):
    DKFZp686N1252    RALGAPA2

    Find genes that share paralogs with TSC2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TSC2 (see all 2593)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 16 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs455027031,2,,4
    CTuberous sclerosis 2 (TSC2)4 untested12041907(+) GATGCG/CGAACC 6 /P /R mis11Minor allele frequency- C:0.00NA 2
    rs455171531,2,,4
    CTuberous sclerosis 2 (TSC2)4 untested12045338(+) CCGAAA/C/TGAGGT 9 K N mis1 syn11NA 2
    rs455173231,2,,4
    C,FTuberous sclerosis 2 (TSC2)4 probable-non-pathogenic12068447(+) CAGGCG/ACACGG 6 /H /R mis13Minor allele frequency- A:0.02WA NA EU 5237
    VAR_0056574
    Tuberous sclerosis 2 (TSC2)4--see VAR_0056572 P L mis40--------
    VAR_0056474
    Tuberous sclerosis 2 (TSC2)4--see VAR_0056472 Y D mis40--------
    VAR_0056504
    Tuberous sclerosis 2 (TSC2)4--see VAR_0056502 R Q mis40--------
    VAR_0094524
    Tuberous sclerosis 2 (TSC2)4--see VAR_0094522 N K mis40--------
    VAR_0056594
    Tuberous sclerosis 2 (TSC2)4--see VAR_0056592 D V mis40--------
    VAR_0056544
    Tuberous sclerosis 2 (TSC2)4--see VAR_0056542 R W mis40--------
    VAR_0080324
    Tuberous sclerosis 2 (TSC2)4--see VAR_0080322 H P mis40--------

    HapMap Linkage Disequilibrium report for TSC2 (2097466 - 2138716 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for TSC2 (see all 29):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2750376CNV Deletion23290073
    nsv471381CNV Duplication19718026
    esv2422427CNV Duplication17116639
    dgv2545n71CNV Loss21882294
    nsv827504CNV Loss20364138
    dgv2546n71CNV Loss21882294
    nsv905048CNV Loss21882294
    nsv905101CNV Loss21882294
    dgv2540n71CNV Loss21882294
    nsv905102CNV Loss21882294

    Human Gene Mutation Database (HGMD): TSC2
    Locus Specific Mutation Databases (LSDB): TSC2

    Selected Site Specific Mutation Identification with PCR Assays for TSC2 (see all 18):
    Cosmic IdAA Change
    76842p.Y1608D
    85612p.E793fs*9
    73090p.M1029I
    48826p.V472M
    87827p.A1141V
    SeqTarget long-range PCR primers for resequencing TSC2
    DNA2.0 Custom Variant and Variant Library Synthesis for TSC2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 191092   
    OMIM disorders: 613254  606690  
    UniProtKB/Swiss-Prot: TSC2_HUMAN, P49815
  • Tuberous sclerosis 2 (TSC2) [MIM:613254]: An autosomal dominant multi-system disorder that affects
    especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths
    predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental
    abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral
    problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of
    disease-associated causes. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Lymphangioleiomyomatosis (LAM) [MIM:606690]: Progressive and often fatal lung disease characterized by a
    diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and
    can occur as an isolated disorder or in association with tuberous sclerosis complex. Note=The disease is caused
    by mutations affecting the gene represented in this entry

  • 20 diseases for TSC2:    
    About MalaCards
    subependymoma    tuberous sclerosis, type 2    tuberous sclerosis complex    lymphangioleiomyomatosis, somatic
    lymphangioleiomyomatosis    angiomyolipoma    tuberous sclerosis    autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
    kidney angiomyolipoma    tsc2 angiomyolipomas, renal, modifier of    lymphangiomatosis    angiomatosis
    perivascular epithelioid cell tumor    hereditary renal cell carcinoma    subependymal giant cell astrocytoma    horseshoe kidney
    cowden disease    peutz-jeghers syndrome    hemimegalencephaly    aortic disease

    11 diseases from the University of Copenhagen DISEASES database for TSC2:
    Tuberous sclerosis     Lymphangioleiomyomatosis     Angiomyolipoma     Kidney angiomyolipoma
    Intellectual disability     Subependymal giant cell astrocytoma     Genetic disorder     Polycystic kidney disease
    Autistic disorder     Kidney cancer     Perivascular epithelioid cell tumor

    Find genes that share disorders with TSC2           About GenesLikeMe

    Selected Novoseek inferred disease relationships for TSC2 gene (see all 73)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tuberous sclerosis 98.5 487 9007104 (4), 9444353 (4), 15072102 (3), 11307618 (3) (see all 99)
    lymphangioleiomyomatosis 92 26 11406664 (2), 16424383 (2), 17114346 (2), 12045200 (2) (see all 19)
    hamartoma 90.5 76 9310961 (4), 11468687 (3), 11112665 (2), 12773159 (2) (see all 52)
    angiomyolipoma 89 72 10823953 (3), 12010366 (3), 9529362 (3), 19265534 (3) (see all 30)
    astrocytoma subependymal giant cell 87.4 18 15072102 (5), 9310961 (2), 16237225 (1), 10805093 (1) (see all 8)
    lymphangiomyomatosis 78.8 3 11208653 (1), 9529362 (1)
    kidney angiomyolipoma 78.3 5 12192641 (2), 11355103 (1), 19005330 (1), 19265534 (1)
    rhabdomyoma 78.2 10 16940165 (3), 16877242 (2), 16554133 (1), 12202993 (1) (see all 6)
    angiofibroma 77.5 17 12641776 (6), 11553313 (2), 18835623 (1), 16965334 (1) (see all 5)
    adpkd 71.4 22 15007723 (2), 9306341 (2), 9631851 (1), 16567633 (1) (see all 15)

    Genatlas disease: TSC2
    tuberous sclerosis 2,multisystem disorder characterized by the widespread development of hamartomatous growths
    noteworthy in eyes,heart,skin and brain,with seizures,behavioral disorder and a renal angiomyolipoma and
    lymphangiomatosis,with a high risk of mental retardation

    GeneTests: TSC2
    GeneReviews: TSC2
    Genetic Association Database (GAD): TSC2
    Human Genome Epidemiology (HuGE) Navigator: TSC2 (20 documents)

    Export disorders for TSC2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TSC2 gene, integrated from 10 sources (see all 652):
    (articles sorted by number of sources associating them with TSC2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and mouse tissues. (PubMed id 7558029)1, 2, 3 Xu L.... Ramesh V. (Genomics 1995)
    2. TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the HERC1 ubiquitin ligase. (PubMed id 16464865)1, 2, 9 Chong-Kopera H.... Guan K.-L. (J. Biol. Chem. 2006)
    3. The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis. (PubMed id 9302281)1, 2, 9 Maheshwar M.M.... Sampson J.R. (Hum. Mol. Genet. 1997)
    4. Novel TSC2 mutations and decreased expression of tuberin in cultured tumor cells with an insertion mutation. (PubMed id 15024740)1, 2, 9 Feng J.-H.... Ohno K. (Hum. Mutat. 2004)
    5. Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. (PubMed id 15798777)1, 4, 9 Sancak O....van den Ouweland A. (Eur. J. Hum. Genet. 2005)
    6. Comprehensive mutation analysis of TSC1 and TSC2- and phenotypic correlations in 150 families with tuberous sclerosis. (PubMed id 10205261)1, 2, 9 Jones A.C.... Cheadle J.P. (Am. J. Hum. Genet. 1999)
    7. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. (PubMed id 9580671)1, 2, 9 van Slegtenhorst M.A.... van der Sluijs P. (Hum. Mol. Genet. 1998)
    8. Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients. (PubMed id 8824881)1, 2, 9 Wilson P.J.... Haines J.L. (Hum. Mol. Genet. 1996)
    9. TSC2 mediates cellular energy response to control cell growth and survival. (PubMed id 14651849)1, 2, 9 Inoki K.... Guan K.L. (Cell 2003)
    10. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. (PubMed id 11112665)1, 4, 9 Dabora S.L....Kwiatkowski D.J. (Am. J. Hum. Genet. 2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 7249 HGNC: 12363 AceView: TSC2 Ensembl:ENSG00000103197 euGenes: HUgn7249
    ECgene: TSC2 Kegg: 7249 H-InvDB: TSC2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for TSC2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TSC2 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=TSC2[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TSC2 gene:
    Search GeneIP for patents involving TSC2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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     genOway: Develop your customized and physiologically relevant rodent model for TSC2
     antibodies-online antibodies for TSC2 (487 products)
     antibodies-online kits for TSC2 (4 products)
     antibodies-online peptides for TSC2
     antibodies-online proteins for TSC2 (2 products)
           
    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014 , 7 Oct 2014

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