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FLASH GENE
Symbol TCF7L2 contributors: mct/pgu - updated : 27-12-2018
HGNC name transcription factor 7-like 2 (T-cell specific, HMG-box)
HGNC id 11641
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
  • 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
    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
  • FRMD5 is a novel direct target of the CTNNB/TCF7L2 complex
    • 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
    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
    Susceptibility
  • 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
    Marker
    Therapy target
    ANIMAL & CELL MODELS