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FLASH GENE
Symbol TCF7L2 contributors: mct/pgu - updated : 27-12-2016
HGNC name transcription factor 7-like 2 (T-cell specific, HMG-box)
HGNC id 11641
Location 10q25.3      Physical location : 114.710.008 - 114.927.434
Synonym name
  • transcription factor 7-like 2
  • HMG box transcription factor 4
  • T cell factor 4
  • transcription factor 7-like 2
  • Synonym symbol(s) TCF4, RP11-357H24.1, TCF-4
    DNA
    TYPE functioning gene
    STRUCTURE 217.46 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence alternative promoter
    text structure two putative alternative promoters in intron 3
    MAPPING cloned Y linked N status provisional
    Physical map
    MXI1 10q25 MAX interacting protein 1 SMNDC1 10q23 survival motor neuron domain containing 1 DUSP5 10q25 dual specificity phosphatase 5 CSPG6 10q25 chondroitin sulfate proteoglycan 6 (bamacan) LOC340699 10q25.3 similar to 1110018J23Rik protein PDCD4 10q24 programmed cell death 4 (neoplastic transformation inhibitor) SHOC2 10q25 soc-2 suppressor of clear homolog (C. elegans) ADRA2A 10q25 adrenergic, alpha-2A-, receptor KIAA1560 10q25.3 glycerol 3-phosphate acyltransferase, mitochondrial TECTB 10q25-q26 tectorin beta LOC390003 10 similar to guanylyl cyclase with kinase-like domain, soluble FACL5 10q25.1-q25.2 fatty-acid-Coenzyme A ligase, long-chain 5 ZDHHC6 10q26.11 zinc finger, DHHC domain containing 6 VTI1A 10q26.11 vesicle transport through interaction with t-SNAREs homolog 1A (yeast) TCF7L2 10q25.3 transcription factor 7-like 2 (T-cell specific, HMG-box) FLJ23556 10q26.11 hypothetical protein FLJ23556 LOC390004 10 similar to peptidylprolyl isomerase E (cyclophilin E) HABP2 10q26.11 hyaluronan binding protein 2 NRAP 10q23-q26 nebulin-related anchoring protein CASP7 10q25.1-q25.2 caspase 7, apoptosis-related cysteine protease FLJ23537 10q26.11 hypothetical protein FLJ23537 DCLRE1A 10q25.1 DNA cross-link repair 1A (PSO2 homolog, S. cerevisiae) FLJ25621 10q26.11 FLJ25621 protein FLJ20147 10q26.11 hypothetical protein FLJ20147 ADRB1 10q24.3 adrenergic, beta-1-, receptor FLJ10188 10q26.11 CTCL tumor antigen L14-2 TDRD1 10q24.1-q25.3 tudor domain containing 1 AMACO 10q26.11 A-domain containing protein similar to matrilin and collagen STK6LP 10q25-q26 serine/threonine kinase 6-like pseudogene LOC390005 10 similar to AMACO FLJ14564 10q26.11 hypothetical protein FLJ14564 ABLIM1 10q25 actin binding LIM protein 1 LOC390006 10 similar to peptidylprolyl isomerase A (cyclophilin A) KIAA1600 10q26.11 KIAA1600 protein TRUB1 10q26.11 TruB pseudouridine (psi) synthase homolog 1 (E. coli) KIAA0534 10q26 KIAA0534 protein
    RNA
    TRANSCRIPTS type messenger
    text
  • complex alternative splicing pattern producing theoretically at least 256 forms, with five alternative exons 4, 13, 14, 15, 16 and an alternative use of three consecutive 3' exons changes the reading frame in the last exon (17) leading to the synthesis of a number of isoforms with short, medium or long-size C terminal ends
  • expression of TCF7L2 alternative exons represents a tissue-specific signature; a unique splicing form of TCF7L2 is expressed in pancreatic islets, pancreas and colon but not in other tissues examined here; expression of this splicing form correlates with expression of proinsulin in glucose-stimulated pancreatic islets; expression of alternatively spliced forms of TCF7L2 in eight human tissues examined here is not associated with T2D-associated risk variants (PMID: 19602480)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 4021 - 489 - 2000 10919662
    long Cter
    14 - 4022 - 602 - 2000 10919662
    long C ter
    14 - 4004 - 596 - 2000 10919662
  • TCF4E
  • medium C ter
  • use alternative transcription start site TSS1, located at 536 bp from the first translation start site
  • acetylated at lysine K&
  • 8321;&8325;&8320; by CREBBP
    13 - 3919 - 455 - 2000 10919662
    long C ter
    11 - 3778 - 408 - 2012 23086040
  • short TCF7L2 mRNA variant in subcutaneous fat regulated by weight loss and associated with hyperglycemia and impaired insulin action in adipose tissue
  • 13 - 3953 63.47 579 - 2000 10919662
  • TCF4J
  • TCF-4J and TCF-4K differed by only five amino acids (the SxxSS motif)
  • its expression produced striking features of malignant transformation characterized by high cell proliferation rate, migration and colony formation even though its transcriptional activity was low
  • 13 - 3949 51.79 465 - 2000 10919662
  • TCF4G
  • 15 - 4092 - 476 - 2000 10919662
  • TCF4I
  • 15 - 4029 - 459 - 2000 10919662
    13 - 3931 - 459 - 2000 10919662
    13 - 3953 - 579 - 2000 10919662
  • TCF4K
  • TCF-4J and TCF-4K differed by only five amino acids (the SxxSS motif)
  • displayed low TCF transcriptional activity; cell proliferation rate and colony formation were reduced as well
  • 12 - 3880 49.17 442 - 2000 10919662
  • TCF4B
  • 15 - 4017 - 455 - 2000 10919662
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Reproductivefemale systembreastmammary gland highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelial    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a CTNNB binding domain
  • a HMG box DNA-binding domain
  • two CtBP binding motifs only present in the long size C terminal isoforms
  • HOMOLOGY
    Homologene
    FAMILY
  • TCF/LEF family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • segment polarity protein, acting as a transcriptional activator
  • high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis
  • may play a role in both glucose homeostasis and adipogenesis (have an inhibitory role of adipogenesis)
  • controls insulin gene expression and insulin secretion in mature pancreatic beta-cells
  • may be having pleiotropic tissue-specific roles and alterations in one or more of these functions could lead to T2 Diabetes
  • plays a key role in TGFB-mediated activation of the PMEPA1 gene
  • important transcription factor in WNT pathway, playing critical roles in oligodendrocyte development
  • key role for TCF7L2 in myelination/remyelination processes via a tightly controlled activation of WNT/CTNNB1 pathway and the interaction with OLIG2
  • likely a crucial role of TCF7L2 in hepatic glucose metabolism
  • WNT/TCF7L2-dependent signaling could play a role in extravillous trophoblasts (EVTs) differentiation promoting motility and expression of promigratory genes
  • is a master regulator of insulin production and processing
  • is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries
  • plays a cell autonomous role in the control of beta cell function and mass, serving as an important regulator of gene expression and islet cell coordination
  • plays key roles in glucose metabolism through actions beyond pancreatic beta cells, but with functionally opposing cell-type specific effects on the maintenance of balanced glucose metabolism
  • TCF7L2, a CTNNB1 transcriptional partner, is required for oligodendrocyte differentiation
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    Wnt (APC/beta catenin/TCF pathway)
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MAD2L2-binding protein (interaction abolished the DNA binding ability of TCF7L2)
  • AES interacts with T-cell factor 4 (TCF7L2) and downregulates WNT signaling
  • tissue-specific differences in the regulation of WWC1 gene expression involve transcription factor TCF7L2 and a complex alternative promoter system
  • TCF7L2 transcriptionally regulated 29 genes related to glucose metabolism, including glucose-6-phosphatase
  • during oligodendrocyte maturation, TCF7L2 recruits and cooperates with SOX10 to promote myelination
  • stage-specific co-regulators ZBTB33 and SOX10 sequentially interact with TCF7L2 to coordinate the switch at the transitions of differentiation initiation and maturation during oligodendrocyte development
  • transcriptional co-activator of CTNNB1
  • cell & other
    REGULATION
    inhibited by insulin
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in gastrointestinal tumor
    tumoral fusion      
    with VTI1A in colorectal cancers
    constitutional     --over  
    attenuated insulin secretion, consistent with the extra TCF7L2 translocating CTNNB1 from the plasma membrane pool to the nucleus
    constitutional     --over  
    may contribute to cartilage degeneration in Osteoarthritis by augmenting NFKB1 signaling
    Susceptibility
  • to type 2 gestational diabetes with alteration of the birth weight
  • to polycystic ovary syndrome
  • to type 2 diabetes (T2D)
  • Variant & Polymorphism SNP
  • increasing thre risk of type 2 diabetes and altering birth weight
  • polymorphisms that may confer an increased risk for early impairment of glucose metabolism in obese children
  • rs11196236 and rs11196229 increasing the risk of polycystic ovary syndrome
  • rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D
  • TCF7L2 rs7903146 polymorphism was associated with susceptibility to gestational diabetes mellitus (GDM)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS