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TCF7L2 Gene

protein-coding   GIFtS: 69
GCID: GC10P114710

Transcription Factor 7-Like 2 (T-Cell Specific, HMG-Box)


(Previous symbol: TCF4)
  See TCF7L2-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
Transcription Factor 7-Like 2 (T-Cell Specific, HMG-Box)1 2     T-Cell Factor-4 Variant E2
TCF41 2 3 5     T-Cell Factor-4 Variant F2
TCF-42 3     T-Cell Factor-4 Variant G2
hTCF-42 3     T-Cell Factor-4 Variant H2
HMG Box Transcription Factor 42 3     T-Cell Factor-4 Variant I2
T-Cell Factor 42 3     T-Cell Factor-4 Variant J2
T-Cell-Specific Transcription Factor 42 3     T-Cell Factor-4 Variant K2
T-Cell Factor-4 Variant A2     T-Cell Factor-4 Variant L2
T-Cell Factor-4 Variant B2     T-Cell Factor-4 Variant M2
T-Cell Factor-4 Variant C2     T-Cell Factor-4 Variant X22
T-Cell Factor-4 Variant D2     Transcription Factor 7-Like 22

External Ids:    HGNC: 116411   Entrez Gene: 69342   Ensembl: ENSG000001487377   OMIM: 6022285   UniProtKB: Q9NQB03   

Export aliases for TCF7L2 gene to outside databases

Previous GC identifers: GC10P113605 GC10P113943 GC10P114841 GC10P114374 GC10P114700 GC10P108337


(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 TCF7L2 Gene:
This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt
signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene
are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different
isoforms have been found for this gene.(provided by RefSeq, Oct 2010)

GeneCards Summary for TCF7L2 Gene:
TCF7L2 (transcription factor 7-like 2 (T-cell specific, HMG-box)) is a protein-coding gene. Diseases associated with TCF7L2 include type 2 diabetes mellitus, and pitt-hopkins syndrome. GO annotations related to this gene include chromatin binding and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is LEF1.

UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0
Function: Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a
sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates
transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1.
TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of
dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial
stem-cell compartment of the small intestine

Gene Wiki entry for TCF7L2 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_000010.10  NT_030059.14  NC_018921.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TCF7L2 gene promoter:
         N-Myc   PPAR-gamma1   STAT3   PPAR-gamma2   AP-2alpha   HNF-4alpha1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): TCF7L2 promoter sequence
   Search Chromatin IP Primers for TCF7L2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TCF7L2


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

Entrez Gene cytogenetic band: 10q25.3   Ensembl cytogenetic band:  10q25.2   HGNC cytogenetic band: 10q25.3

TCF7L2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TCF7L2 gene location

GeneLoc information about chromosome 10         GeneLoc Exon Structure

GeneLoc location for GC10P114710:  view genomic region     (about GC identifiers)

Start:
114,710,009 bp from pter      End:
114,927,437 bp from pter
Size:
217,429 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., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0 (See protein sequence)
Recommended Name: Transcription factor 7-like 2  
Size: 619 amino acids; 67919 Da
Subunit: Interacts with TGFB1I1 (By similarity). Interacts with CTNNB1 (via the armadillo repeat); forms stable
transcription complex. Interacts with EP300. Interacts with NLK. Interacts with CCDC85B (probably through the HMG
box); prevents interaction with CTNNB1. Interacts with TNIK. Interacts with MAD2L2; prevents TCF7L2/TCF4 binding
to promZIPK/DAPK3oters, negatively modulating its transcriptional activity. Interacts with ZIPK/DAPK3. Interacts
with XIAP/BIRC4 and TLE3. Interacts with DDIT3/CHOP. The CTNNB1 and TCF7L2/TCF4 complex interacts with PML
(isoform PML-4). Identified in a complex with CTNNB1 and FERMT2
Developmental stage: Highly expressed in crypt regions and barely detectable in villi in epithelium from fetal
small intestine at week 16. At week 22 expression in villi had increased strongly
3 PDB 3D structures from and Proteopedia for TCF7L2:
1JDH (3D)        1JPW (3D)        2GL7 (3D)    
Secondary accessions: B4DRJ8 B9X074 C6ZRJ8 C6ZRK0 E2GH14 E2GH19 E2GH20 E2GH24 E2GH25 E9PFH9
F8W742 F8W7T5 O00185 Q9NQB1 Q9NQB2 Q9NQB3 Q9NQB4 Q9NQB5 Q9NQB6 Q9NQB7 Q9ULC2
Alternative splicing: 17 isoforms:  Q9NQB0-1   Q9NQB0-2   Q9NQB0-3   Q9NQB0-4   Q9NQB0-5   Q9NQB0-6   Q9NQB0-7   Q9NQB0-8   
Q9NQB0-9   Q9NQB0-10   Q9NQB0-11   Q9NQB0-12   Q9NQB0-13   Q9NQB0-14   Q9NQB0-15   Q9NQB0-16   
Q9NQB0-17   (High transcriptional activity. Major isoform in liver)

Explore the universe of human proteins at neXtProt for TCF7L2: NX_Q9NQB0

Explore proteomics data for TCF7L2 at MOPED

Post-translational modifications: 

  • In vitro, phosphorylated by TNIK1
  • Phosphorylated at Thr-201 and/or Thr-212 by NLK. Phosphorylation by NLK at these sites inhibits DNA-binding by
    TCF7L2/TCF4, thereby preventing transcriptional activation of target genes of the canonical Wnt/beta-catenin
    signaling pathway1
  • Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylation is enhanced by SENP2.
    Sumoylation/desumoylation regulates TCF7L2/TCF4 transcription activity in the Wnt/beta-catenin signaling pathway
    without altering interaction with CTNNB1 nor binding to DNA1
  • Ubiquitination2 at Lys352, Lys398
  • Modification sites at PhosphoSitePlus

  • See TCF7L2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (13 alternative transcripts): 
    NP_001139746.1  NP_001139755.1  NP_001139756.1  NP_001139757.1  NP_001139758.1  NP_001185454.1  NP_001185455.1  NP_001185456.1  
    NP_001185457.1  NP_001185458.1  NP_001185459.1  NP_001185460.1  NP_110383.2  

    ENSEMBL proteins: 
     ENSP00000298692   ENSP00000358404   ENSP00000358402   ENSP00000345640   ENSP00000358396  
     ENSP00000277945   ENSP00000358393   ENSP00000435694   ENSP00000348274   ENSP00000440547  
     ENSP00000444972   ENSP00000446238   ENSP00000347949   ENSP00000446172   ENSP00000344823  
     ENSP00000443626   ENSP00000443883  
    Reactome Protein details: Q9NQB0

    TCF7L2 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for TCF7L2
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    Novus Biologicals TCF7L2 Proteins
    Novus Biologicals TCF7L2 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for TCF7L2

     
    Search eBioscience for Proteins for TCF7L2 

    TCF7L2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TCF7L2
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    Abcam antibodies for TCF7L2
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    ThermoFisher Antibodies for TCF7L2
    LSBio Antibodies in human, mouse, rat for TCF7L2

    TCF7L2 Assay Products:

    EMD Millipore Kits and Assays for the Analysis of TCF7L2
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    GenScript Custom Assay Services for TCF7L2
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for TCF7L2
    Cloud-Clone Corp. CLIAs for TCF7L2
    Search eBioscience for ELISAs for TCF7L2 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    5 InterPro protein domains:
     IPR027397 Catenin_binding_dom
     IPR009071 HMG_box_dom
     IPR028773 TCF7L2
     IPR024940 TCF/LEF
     IPR013558 CTNNB1-bd_N

    Graphical View of Domain Structure for InterPro Entry Q9NQB0

    ProtoNet protein and cluster: Q9NQB0

    1 Blocks protein domain: IPB013558 CTNNB1 binding

    UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0
    Domain: The promoter-specific activation domain interacts with the transcriptional coactivator EP300
    Similarity: Belongs to the TCF/LEF family
    Similarity: Contains 1 HMG box DNA-binding domain


    Find genes that share domains with TCF7L2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, 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: TF7L2_HUMAN, Q9NQB0
    Function: Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a
    sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates
    transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1.
    TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of
    dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial
    stem-cell compartment of the small intestine

         Gene Ontology (GO): Selected molecular function terms (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000978RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA19443654
    GO:0001103RNA polymerase II repressing transcription factor binding IPI19443654
    GO:0003682chromatin binding IBA--
    GO:0003700sequence-specific DNA binding transcription factor activity IDA9727977
    GO:0005515protein binding IPI11713475
         
    Find genes that share ontologies with TCF7L2           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for TCF7L2:
     Increased S DNA content  Increased cell death in breast  Increased gamma-H2AX phosphory 

         14 MGI mutant phenotypes (inferred from 12 alleles(MGI details for Tcf7l2):
     adipose tissue  behavior/neurological  cellular  craniofacial  digestive/alimentary 
     endocrine/exocrine gland  growth/size/body  homeostasis/metabolism  integument  liver/biliary system 
     mortality/aging  muscle  nervous system  tumorigenesis 

    Find genes that share phenotypes with TCF7L2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for TCF7L2: Tcf7l2tm1Cle Tcf7l2tm2.2Mrc

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TCF7L2
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TCF7L2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TCF7L2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TCF7L2

    Transcription Factor Targeting: 
    Targeting motifs: HOMER Transcription Factor Regulatory Elements motif viewer 
                                          Consensus sequence:  ACATCAAAGGGA 

    miRNA
    Products:
        
    miRTarBase miRNAs that target TCF7L2:
    hsa-mir-148b-3p (MIRT043583), hsa-mir-324-5p (MIRT043052)

    Block miRNA regulation of human, mouse, rat TCF7L2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TCF7L2 (see all 106):
    hsa-miR-411* hsa-miR-218-1* hsa-miR-1258 hsa-miR-485-3p hsa-miR-938 hsa-miR-877* hsa-miR-3161 hsa-miR-629
    SwitchGear 3'UTR luciferase reporter plasmidTCF7L2 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TCF7L2
    Predesigned siRNA for gene silencing in human, mouse, rat TCF7L2

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for TCF7L2

    Clone
    Products:
         
    OriGene clones in human, mouse for TCF7L2 (see all 52)
    OriGene ORF clones in mouse, rat for TCF7L2
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 13): TCF7L2 (NM_001146284)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TCF7L2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TCF7L2
    Addgene plasmids for TCF7L2 

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    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TCF7L2

    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA1-11983 VA4-11293) for TCF7L2 


    (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
    TF7L2_HUMAN, Q9NQB0: Nucleus, PML body. Note=Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML
    (promyelocytic leukemia) nuclear bodies
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol3

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000790nuclear chromatin IDA19443654
    GO:0005634nucleus IDA--
    GO:0005654nucleoplasm TAS--
    GO:0005667transcription factor complex IBA--
    GO:0005730NOT nucleolus IDA--

    Find genes that share ontologies with TCF7L2           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 TCF7L2 About   (see all 27)  
    See pathways by source

    SuperPathContained pathways About
    1Endometrial cancer
    Endometrial cancer0.45
    Colorectal cancer0.42
    Signal transduction PTEN pathway0.45
    Acute myeloid leukemia0.40
    2Hypertrophic cardiomyopathy (HCM)
    Arrhythmogenic right ventricular cardiomyopathy (ARVC)0.54
    Arrhythmogenic right ventricular cardiomyopathy0.54
    3Wnt signaling pathway (KEGG)
    Wnt signaling pathway0.40
    Wnt Signaling Pathways0.40
    4beta-catenin independent WNT signaling
    beta-catenin independent WNT signaling0.79
    Ca2+ pathway0.43
    Signaling by Wnt0.79
    5Incretin Synthesis, Secretion, and Inactivation
    Incretin Synthesis, Secretion, and Inactivation0.88
    Synthesis, Secretion, and Inactivation of Glucagon-like Peptide-1 (GLP-1)0.88


    Find genes that share SuperPaths with TCF7L2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for TCF7L2
        Wnt Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TCF7L2 (see all 7)
        MAPK Signaling
    ILK Signaling
    Factors Promoting Cardiogenesis in Vertebrates
    Human Embryonic Stem Cell Pluripotency
    JNK Pathway

    1 Cell Signaling Technology (CST) Pathway for TCF7L2
        Wnt / Hedgehog / Notch

    Selected GeneGo (Thomson Reuters) Pathways for TCF7L2 (see all 8)
        Cytoskeleton remodeling Integrin outside-in signaling
    Development A2B receptor- action via G-protein alpha s
    Development VEGF signaling via VEGFR2 - generic cascades
    Development A3 receptor signaling
    Development HGF signaling pathway

    4 BioSystems Pathways for TCF7L2
        Wnt Signaling Pathway and Pluripotency
    Id Signaling Pathway
    Arrhythmogenic right ventricular cardiomyopathy
    Regulation of Wnt-mediated beta catenin signaling and target gene transcription

    5 Reactome Pathways for TCF7L2
        deactivation of the beta-catenin transactivating complex
    Ca2+ pathway
    binding of TCF/LEF:CTNNB1 to target gene promoters
    Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
    formation of the beta-catenin:TCF transactivating complex


    Selected Kegg Pathways  (Kegg details for TCF7L2) (see all 12):
        Wnt signaling pathway
    Hippo signaling pathway
    Adherens junction
    Melanogenesis
    Pathways in cancer

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TCF7L2 (see all 6): 
              Parkinson's Disease in human mouse rat
              Stem Cell Transcription Factors in human mouse rat
              WNT Signaling Targets in human mouse rat
              Stem Cell Signaling in human mouse rat
              Transcription Factors in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TCF7L2

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

    Selected Interacting proteins for TCF7L2 (Q9NQB01, 2, 3 ENSP000003584044) via UniProtKB, MINT, STRING, and/or I2D (see all 140)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIC1Q145261, 2, 3, ENSP000003140804EBI-924724,EBI-2507362 MINT-2730845 MINT-2730694 MINT-2730765 MINT-2730819 MINT-2730877 MINT-2730798 I2D: score=2 STRING: ENSP00000314080
    TNIKQ9UKE51, 2, 3, ENSP000003995114EBI-924724,EBI-1051794 MINT-7952375 MINT-7952429 MINT-7952386 I2D: score=1 STRING: ENSP00000399511
    ENSG00000206206Q9UER71, 3EBI-924724,EBI-77321 I2D: score=1 
    ENSG00000206279Q9UER71, 3EBI-924724,EBI-77321 I2D: score=1 
    ENSG00000227046Q9UER71, 3EBI-924724,EBI-77321 I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 54):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IDA12799378
    GO:0001568blood vessel development IMP15578569
    GO:0006351transcription, DNA-templated IEA--
    GO:0006355regulation of transcription, DNA-templated ----
    GO:0006357regulation of transcription from RNA polymerase II promoter IDA9727977

    Find genes that share ontologies with TCF7L2           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 TCF7L2 (TF7L2)

    Selected Novoseek inferred chemical compound relationships for TCF7L2 gene (see all 14)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    proglucagon 66.6 1 15525634 (1)
    mononucleotide 53.9 4 18755497 (2), 11746989 (1), 19787250 (1)
    glycogen 50.7 4 20442281 (1), 15525634 (1), 15940626 (1), 19818782 (1)
    glucose 47 13 17697858 (1), 19105201 (1), 16415884 (1), 17437080 (1) (see all 11)
    sulindac 41.5 3 11751639 (1), 14610217 (1)
    lithium chloride 38.4 1 19679347 (1)
    ly294002 33.4 4 19190323 (1)
    phosphatidylinositol 11.7 4 19190323 (1)
    nitric oxide 5.06 1 20096072 (1)
    butyrate 0.698 2 11774242 (1)

    2 PharmGKB related drug/compound annotations for TCF7L2 gene    About this table
    Drug/compound PharmGKB Annotation
    sulfonamides, urea derivativesCA  
    repaglinideCA  



    Find genes that share compounds with TCF7L2           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 TCF7L2 gene (13 alternative transcripts): 
    NM_001146274.1  NM_001146283.1  NM_001146284.1  NM_001146285.1  NM_001146286.1  NM_001198525.1  NM_001198526.1  NM_001198527.1  
    NM_001198528.1  NM_001198529.1  NM_001198530.1  NM_001198531.1  NM_030756.4  

    Unigene Cluster for TCF7L2:

    Transcription factor 7-like 2 (T-cell specific, HMG-box)
    Hs.593995  [show with all ESTs]
    Unigene Representative Sequence: NM_001198525
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 22):
    ENST00000349937 ENST00000369397(uc010qrs.2 uc010qrv.2 uc010qrw.2 uc010qrx.2)
    ENST00000369395 ENST00000346198 ENST00000369389 ENST00000277945 ENST00000369386
    ENST00000466338 ENST00000470254 ENST00000480888 ENST00000471569 ENST00000476887
    ENST00000494353 ENST00000355995(uc021pyg.1 uc021pyi.1 uc010qrp.2 uc010qrq.2 uc001lac.4)
    ENST00000545257(uc001lah.3 uc010qrt.2) ENST00000543371(uc001lae.4 uc021pyk.1 uc021pyn.1 uc010qrl.2)
    ENST00000536810(uc001laf.4) ENST00000355717(uc001lag.4 uc010qrr.2 uc010qru.2)

    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate TCF7L2 (see all 106):
    hsa-miR-411* hsa-miR-218-1* hsa-miR-1258 hsa-miR-485-3p hsa-miR-938 hsa-miR-877* hsa-miR-3161 hsa-miR-629
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    GenScript: all cDNA clones in your preferred vector (see all 13): TCF7L2 (NM_001146284)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TCF7L2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TCF7L2
    Addgene plasmids for TCF7L2 
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    Flow Cytometry
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    eBioscience FlowRNA Probe Sets ( VA1-11983 VA4-11293) for TCF7L2 

    Additional mRNA sequence: 

    AB034691.1 AB440195.1 AB451266.1 AK054578.1 AK074705.1 AK225809.1 AK296305.1 AK299295.1 
    AK301483.1 AK303684.1 AK315243.1 AK316111.1 BC032656.1 BX648364.1 CR536574.1 FJ010164.1 
    FJ010165.1 FJ010166.1 FJ010167.1 FJ010168.1 FJ010169.1 FJ010170.1 FJ010171.1 FJ010172.1 
    FJ010173.1 FJ010174.1 HM352838.1 HM352839.1 HM352840.1 HM352841.1 HM352842.1 HM352843.1 
    HM352844.1 HM352845.1 HM352846.1 HM352847.1 HM352848.1 HM352849.1 HM352850.1 HM352851.1 
    Y11306.2 

    22 DOTS entries:

    DT.100717951  DT.100814194  DT.95371069  DT.95371070  DT.121279537  DT.121279368  DT.110441  DT.97859220 
    DT.121279438  DT.121279575  DT.91742749  DT.100814193  DT.40266758  DT.75100728  DT.121279380  DT.121279454 
    DT.121279480  DT.70101434  DT.99954951  DT.75136202  DT.91856101  DT.99984552 

    Selected AceView cDNA sequences (see all 176):

    AI494086 AU120697 BM702280 AI084440 BM142562 AI868258 BU729078 AW467057 
    BU195676 AI263902 AA812256 T54154 BG057515 AA362301 BM360880 BU617649 
    BM681576 AI933235 CR536574 BM671072 AI168772 AA954024 CA450439 AB034691 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for TCF7L2 (see all 10)    About this scheme

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

    ExUns: 16b ^ 17 ^ 18 ^ 19 ^ 20a · 20b · 20c · 20d · 20e
    SP1:                    -                                 
    SP2:        -     -                                       
    SP3:              -     -                                 
    SP4:                                                      
    SP5:                                                      


    ECgene alternative splicing isoforms for TCF7L2

    (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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    TCF7L2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ATTCTACCAA
    TCF7L2 Expression
    About this image


    TCF7L2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 12) fully expand
     
     Brain (Nervous System)    fully expand to see all 17 entries
             Pre-myelinating Oligodendrocyte Cells Forebrain White Matter
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 10 entries
             Oligodendrocyte Precursor Cells Caudal Ganglionic Eminence
             Metencephalon
     
     Spinal Cord (Nervous System)
             Pre-myelinating Oligodendrocyte Cells Spinal Cord White Matter
     
     Ovary (Reproductive System)    fully expand to see all 3 entries
             Pre-Granulosa Cells Primordial Follicle
             Oviduct
     
     Bone (Muscoskeletal System)    fully expand to see all 2 entries
             Bone Marrow
    TCF7L2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TCF7L2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.593995

    UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0
    Tissue specificity: Detected in epithelium from small intestine, with the highest expression at the top of the
    crypts and a gradient of expression from crypt to villus. Detected in colon epithelium and colon cancer, and in
    epithelium from mammary gland and carcinomas derived therefrom

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TCF7L2 (see all 6): 
              Parkinson's Disease in human mouse rat
              Stem Cell Transcription Factors in human mouse rat
              WNT Signaling Targets in human mouse rat
              Stem Cell Signaling in human mouse rat
              Transcription Factors in human mouse rat

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TCF7L2

    (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)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for TCF7L2 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tcf7l21 , 5 transcription factor 7 like 2, T cell specific, HMG box less1, 5 90.88(n)1
    97.65(a)1
      19 (51.59 cM)5
    214161  NM_001142922.11  NP_001136394.11 
     557418205 
    chicken
    (Gallus gallus)
    Aves TCF7L21 transcription factor 7-like 2 (T-cell specific, HMG-box) less 87.35(n)
    94.94(a)
      395508  NM_001206510.2  NP_001193439.1 
    lizard
    (Anolis carolinensis)
    Reptilia --
    --
    Uncharacterized protein
    94(a)
    85(a)
    1 ↔ many
    1 ↔ many
    AAWZ02039818(1550-4389)
    GL343204.1(1234849-1479528)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.119872 Xenopus laevis T-cell factor 4 mRNA, complete cds 78.33(n)    AF207708.1 
    zebrafish
    (Danio rerio)
    Actinopterygii tcf42 transcription factor tcf4 81.31(n)   30510  AF507957.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta pan3 heart development transcription factor 38(a)     --
    worm
    (Caenorhabditis elegans)
    Secernentea pop-16
    Protein POP-1 (pop-1) mRNA, complete cds
    31(a)
    1 → many
    I(2823468-2830293) WBGene00004077


    ENSEMBL Gene Tree for TCF7L2 (if available)
    TreeFam Gene Tree for TCF7L2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TCF7L2 gene
    LEF12  TCF7L12  TCF72  
    7 SIMAP similar genes for TCF7L2 using alignment to 17 protein entries:     TF7L2_HUMAN (see all proteins):
    DKFZp586H0919    TCF7L1    TCF7    CIC    LEF1    soxB
    SRY

    Find genes that share paralogs with TCF7L2           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 TCF7L2 (see all 5536)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 10 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0359394
    A colorectal cancer sample4--see VAR_0359392 R C mis40--------
    rs721014021,2
    C--108338369(+) TTCTA-/CCCCCC 13 -- int10--------
    rs1123851751,2
    C--108339201(+) AGAACT/-TTTCC 13 -- int11Minor allele frequency- -:0.00CSA 2
    rs57879821,2
    C,F--108341480(+) GTGTGT/-TTTTA 13 -- int12Minor allele frequency- -:0.50NA CSA 4
    rs21045971,2
    C--108343654(-) CATTTA/Taaaaa 13 -- int10--------
    rs350542851,2
    C--108344501(+) TTTTT-/T/TTT 
            
    GAGAT
    13 -- int11NA 2
    rs2006142271,2
    --108348542(+) TGACC-/GCCCCC 13 -- int10--------
    rs1854061041,2
    C--108348543(+) TGACCC/GCCCCC 13 -- int10--------
    rs353744331,2
    C--108354064(+) AATGG-/CAAAAA 13 -- int12Minor allele frequency- C:0.42CSA NS 288
    rs720438901,2
    C--108354066(+) ATGGA-/CAAAAG 13 -- int10--------

    HapMap Linkage Disequilibrium report for TCF7L2 (114710009 - 114927437 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for TCF7L2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2074123CNV Deletion18987734
    nsv437693CNV Loss16327808
    nsv527837CNV Loss19592680
    nsv24033CNV Loss16902084
    nsv7553CNV Loss18451855
    nsv7211OTHER Inversion18451855

    Human Gene Mutation Database (HGMD): TCF7L2
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TCF7L2
    DNA2.0 Custom Variant and Variant Library Synthesis for TCF7L2

    (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.)
    About This Section

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    OMIM gene information: 602228   
    OMIM disorders: 125853  
    UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0
  • Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance
    of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal
    differentiation and constitute the primary transforming event in colorectal cancer (CRC)
  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose
    homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese
    body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance,
    hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes,
    kidneys, nerves, and blood vessels. Note=Disease susceptibility is associated with variations affecting the gene
    represented in this entry

  • 6 diseases for TCF7L2:    
    About MalaCards
    type 2 diabetes mellitus    pitt-hopkins syndrome    tropical calcific pancreatitis    acute insulin response
    colorectal cancer    prostate cancer

    1 disease from the University of Copenhagen DISEASES database for TCF7L2:
    Diabetes mellitus

    Find genes that share disorders with TCF7L2           About GenesLikeMe

    Selected Novoseek inferred disease relationships for TCF7L2 gene (see all 30)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    familial adenomatous polyposis 70.6 5 14610217 (1), 10080941 (1), 15591320 (1), 15972967 (1)
    colon cancer 61.9 21 11876551 (2), 18268068 (2), 18398040 (2), 18182714 (1) (see all 13)
    colorectal tumors 59.2 8 18992165 (2), 11528255 (2), 11980438 (1), 17408638 (1) (see all 5)
    microsatellite instability 57.3 9 17659738 (2), 10485457 (1), 11876551 (1), 15905022 (1) (see all 8)
    colorectal cancer 53.2 18 16547505 (3), 19924301 (3), 10919662 (2), 10485457 (1) (see all 10)
    niddm 50.2 19 19386626 (2), 18599616 (2), 17697858 (1), 18291022 (1) (see all 11)
    insulin sensitivity 49.2 5 18398040 (1)
    insulin resistance 45.1 2 16936218 (1), 20107109 (1)
    colorectal carcinoma 44.9 1 15802015 (1)
    colon carcinoma 43.3 1 10549354 (1)

    Genetic Association Database (GAD): TCF7L2
    Human Genome Epidemiology (HuGE) Navigator: TCF7L2 (244 documents)

    Export disorders for TCF7L2 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 TCF7L2 gene, integrated from 10 sources (see all 597):
    (articles sorted by number of sources associating them with TCF7L2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. (PubMed id 16415884)1, 2, 4, 9 Grant S.F.A.... Stefansson K. (Nat. Genet. 2006)
    2. Association of hTcf-4 gene expression and mutation with clinicopathological characteristics of hepatocellular carcinoma. (PubMed id 12378619)1, 4, 9 Jiang Y....Huang X.W. (World J. Gastroenterol. 2002)
    3. Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium. (PubMed id 9916915)1, 2, 9 Barker N.... Clevers H. (Am. J. Pathol. 1999)
    4. Evaluation of a variant in the transcription factor 7-like 2 (TCF7L2) gene and prostate cancer risk in a population-based study. (PubMed id 18302196)1, 4, 9 Agalliu I....Ostrander E.A. (Prostate 2008)
    5. Transcription factor 7-like 2 (TCF7L2) variant is associated with familial breast cancer risk: a case-control study. (PubMed id 17109766)1, 4, 9 Burwinkel B....Frank B. (BMC Cancer 2006)
    6. No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue. (PubMed id 19895682)1, 4, 9 Prokunina-Olsson L. and Hall J.L. (Mol. Cancer 2009)
    7. Variation in TCF7L2 and increased risk of colon cancer: the Atherosclerosis Risk in Communities (ARIC) Study. (PubMed id 18268068)1, 4, 9 Folsom A.R....Boerwinkle E. (Diabetes Care 2008)
    8. Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS. (PubMed id 17805508)1, 4, 9 Barber T.M....McCarthy M.I. (Diabetologia 2007)
    9. Identification of Tcf4 residues involved in high-affinity beta- catenin binding. (PubMed id 10080941)1, 2, 9 Omer C.A.... Kral A.M. (Biochem. Biophys. Res. Commun. 1999)
    10. Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes. (PubMed id 17003360)1, 4, 9 Cauchi S....Froguel P. (Diabetes 2006)

    (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: 6934 HGNC: 11641 AceView: TCF7L2 Ensembl:ENSG00000148737 euGenes: HUgn6934
    ECgene: TCF7L2 Kegg: 6934 H-InvDB: TCF7L2

    (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)
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    NameDescription
    PharmGKB entry for TCF7L2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TCF7L2 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TCF7L2 gene:
    Search GeneIP for patents involving TCF7L2

    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, LSBio, eBioscience, 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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