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Transcription factor 7-like 2 (T-cell specific, HMG-box)
Protein TCF7L2 PDB 1jdh.png
PDB rendering based on 1jdh.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols TCF7L2 ; TCF-4; TCF4
External IDs OMIM602228 MGI1202879 HomoloGene7564 GeneCards: TCF7L2 Gene
RNA expression pattern
PBB GE TCF7L2 212759 s at tn.png
PBB GE TCF7L2 212761 at tn.png
PBB GE TCF7L2 212762 s at tn.png
More reference expression data
Species Human Mouse
Entrez 6934 21416
Ensembl ENSG00000148737 ENSMUSG00000024985
UniProt Q9NQB0 Q924A0
RefSeq (mRNA) NM_001146274 NM_001142918
RefSeq (protein) NP_001139746 NP_001136390
Location (UCSC) Chr 10:
112.95 – 113.17 Mb
Chr 19:
55.74 – 55.93 Mb
PubMed search [1] [2]

Transcription factor 7-like 2 (T-cell specific, HMG-box) also known as TCF7L2 or TCF4 is a protein acting as a transcription factor. In humans this protein is encoded by the TCF7L2 gene.[1][2] The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker[3] associated with Type 2 diabetes mellitus (T2DM) risk. SNPs in this gene are linked to higher risk to develop type 2 diabetes,[4] as well as gestational diabetes.[5]

Structure of complex between TCF7L2 (orange), β-catenin (red), and BCL9 (brown).[6]


TCF7L2 is a transcription factor influencing the transcription of several genes thereby exerting a large variety of functions within the cell. It is a member of the Wnt signaling pathway. Stimulation of the pathway leads to the association of β-catenin with BCL9, translocation to the nucleus, and association with TCF7L2,[7] which in turn results in the activation of Wnt target genes, specifically repressing proglucagon synthesis in enteroendocrine cells.[4][8]

Clinical significance[edit]

TCF7L2 is implicated in a large variety of diseases. Several single nucleotide polymorphisms are associated with type 2 diabetes. In European populations it was found to be a major determinant of type 2 risk.[4]

A frameshift mutation of TCF7L2 is implicated in colorectal cancer.[9][10] Variants of the gene are most likely involved in many other cancer types.[11]

Model organisms[edit]

Model organisms have been used in the study of TCF7L2 function. A conditional knockout mouse line called Tcf7l2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[12] Male and female animals underwent a standardized phenotypic screen[13] to determine the effects of deletion.[14][15][16][17] Additional screens performed: - In-depth immunological phenotyping[18]


While TCF4 is sometimes used as an alias symbol for TCF7L2, it is also the symbol officially approved by the HUGO Gene Nomenclature Committee for the transcription factor 4 gene.

See also[edit]


  1. ^ "Entrez Gene: TCF7L2". 
  2. ^ Castrop J, van Norren K, Clevers H (1992). "A gene family of HMG-box transcription factors with homology to TCF-1". Nucleic Acids Res. 20 (3): 611. doi:10.1093/nar/20.3.611. PMC 310434. PMID 1741298. 
  3. ^ Vaquero AR, Ferreira NE, Omae SV, Rodrigues MV, Teixeira SK, Krieger JE et al. (2012). "Using gene-network landscape to dissect genotype effects of TCF7L2 genetic variant on diabetes and cardiovascular risk". Physiol. Genomics 44 (19): 903–14. doi:10.1152/physiolgenomics.00030.2012. PMID 22872755. 
  4. ^ a b c Jin T, Liu L (2008). "The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus". Mol. Endocrinol. 22 (11): 2383–92. doi:10.1210/me.2008-0135. PMID 18599616. 
  5. ^ Zhang C, Bao W, Rong Y, Yang H, Bowers K, Yeung E et al. (2013). "Genetic variants and the risk of gestational diabetes mellitus: a systematic review". Hum. Reprod. Update 19 (4): 376. doi:10.1093/humupd/dmt013. PMID 23690305. 
  6. ^ PDB: 2GL7 ; Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W (October 2006). "Crystal structure of a beta-catenin/BCL9/Tcf4 complex". Mol. Cell 24 (2): 293–300. doi:10.1016/j.molcel.2006.09.001. PMID 17052462. 
  7. ^ Lee JM, Dedhar S, Kalluri R, Thompson EW (2006). "The epithelial-mesenchymal transition: new insights in signaling, development, and disease". J. Cell Biol. 172 (7): 973–81. doi:10.1083/jcb.200601018. PMC 2063755. PMID 16567498. 
  8. ^ Online 'Mendelian Inheritance in Man' (OMIM) 602228
  9. ^ Slattery ML, Folsom AR, Wolff R, Herrick J, Caan BJ, Potter JD (2008). "Transcription factor 7-like 2 polymorphism and colon cancer". Cancer Epidemiol. Biomarkers Prev. 17 (4): 978–82. doi:10.1158/1055-9965.EPI-07-2687. PMC 2587179. PMID 18398040. 
  10. ^ Hazra A, Fuchs CS, Chan AT, Giovannucci EL, Hunter DJ (2008). "Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk". Cancer Causes Control 19 (9): 975–80. doi:10.1007/s10552-008-9164-3. PMC 2719293. PMID 18478343. 
  11. ^ Tang W, Dodge M, Gundapaneni D, Michnoff C, Roth M, Lum L (2008). "A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer". Proc. Natl. Acad. Sci. U.S.A. 105 (28): 9697–702. Bibcode:2008PNAS..105.9697T. doi:10.1073/pnas.0804709105. PMC 2453074. PMID 18621708. 
  12. ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley. 
  13. ^ a b "International Mouse Phenotyping Consortium". 
  14. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750. 
  15. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  16. ^ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  17. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN et al. (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMID 23870131. 
  18. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium". 

Further reading[edit]

External links[edit]

  • TCF7L2 here called TCF4 features on this Wnt pathway web site: Wnt signalling molecules TCFs
  • Structure determination of TCF7L2: PDB entry 2GL7 and related publication on PubMed
  • PubMed GeneRIFs (summaries of related scientific publications) - [3]
  • Weizmann Institute GeneCard for TCF7L2