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Symbol TCF7L2 contributors: mct/pgu - updated : 27-12-2018
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
    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
    TRANSCRIPTS type messenger
  • 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
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Reproductivefemale systembreastmammary gland highly
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • a CTNNB binding domain
  • a HMG box DNA-binding domain
  • two CtBP binding motifs only present in the long size C terminal isoforms
  • TCF/LEF family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    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
  • TCF7L2 directly activates metabolic genes
  • 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
    signaling signal transduction
    Wnt (APC/beta catenin/TCF pathway)
    a component
    small molecule
  • 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
    inhibited by insulin
    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
    constitutional       gain of function
    is associated with BCL2 repression promoting vascular smooth muscle cell apoptosis, a key driver of TAA disease
    constitutional     --over  
    may result in enhanced apoptosis of vascular smooth muscle cells—a likely mechanism of action of TAA-associated variants in TCF7L2
  • to type 2 gestational diabetes with alteration of the birth weight
  • to polycystic ovary syndrome
  • to type 2 diabetes (T2D)
  • to Thoracic aortic aneurysm (TAA)
  • 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)
  • variants within the third intron of TCF7L2 significantly associated with TAA
  • Candidate gene
    Therapy target