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Gene Review

TCF7L2  -  transcription factor 7-like 2 (T-cell...

Homo sapiens

Synonyms: HMG box transcription factor 4, T-cell factor 4, T-cell-specific transcription factor 4, TCF-4, TCF4, ...
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Disease relevance of TCF7L2

  • METHODS: We investigated the effect of the TCF7L2 rs12255372 variant on familial breast cancer (BC) risk by means of TaqMan allelic discrimination, analyzing BRCA1/2 mutation-negative index patients of 592 German BC families and 735 control individuals [1].
  • We conclude that the TCF7L2 T at-risk allele variation (rs7903146) predicts hyperglycemia incidence in a general French population, possibly through a deleterious effect on insulin secretion [2].
  • Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population [3].
  • Additionally, we find that hypoxia inducible factor-1alpha (HIF-1alpha) competes with TCF-4 for direct binding to beta-catenin [4].
  • Mutations in the Wnt components AXIN1, AXIN2 and TCF4 have been found in microsatellite-unstable colon cancers, but it is not clear in every case whether these changes are functional [5].

High impact information on TCF7L2


Biological context of TCF7L2


Anatomical context of TCF7L2


Associations of TCF7L2 with chemical compounds


Other interactions of TCF7L2

  • CONCLUSION: The TCF7L2 rs7903146 polymorphism is associated with lower insulin levels, smaller waist circumference, and lower risk lipid profiles in the general elderly population [20].
  • METHODS AND FINDINGS: Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to predispose to type 2 diabetes mellitus across many large studies [21].
  • We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, approximately 1 Mb from TCF7L2, in the Finland-United States Investigation of NIDDM Genetics study [22].

Analytical, diagnostic and therapeutic context of TCF7L2


  1. Transcription factor 7-like 2 (TCF7L2) variant is associated with familial breast cancer risk: a case-control study. Burwinkel, B., Shanmugam, K.S., Hemminki, K., Meindl, A., Schmutzler, R.K., Sutter, C., Wappenschmidt, B., Kiechle, M., Bartram, C.R., Frank, B. BMC Cancer (2006) [Pubmed]
  2. TCF7L2 Variation Predicts Hyperglycemia Incidence in a French General Population: The Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) Study. Cauchi, S., Meyre, D., Choquet, H., Dina, C., Born, C., Marre, M., Balkau, B., Froguel, P. Diabetes (2006) [Pubmed]
  3. Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Chandak, G.R., Janipalli, C.S., Bhaskar, S., Kulkarni, S.R., Mohankrishna, P., Hattersley, A.T., Frayling, T.M., Yajnik, C.S. Diabetologia (2007) [Pubmed]
  4. Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia. Kaidi, A., Williams, A.C., Paraskeva, C. Nat. Cell Biol. (2007) [Pubmed]
  5. Colorectal cancer and genetic alterations in the Wnt pathway. Segditsas, S., Tomlinson, I. Oncogene (2006) [Pubmed]
  6. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Grant, S.F., Thorleifsson, G., Reynisdottir, I., Benediktsson, R., Manolescu, A., Sainz, J., Helgason, A., Stefansson, H., Emilsson, V., Helgadottir, A., Styrkarsdottir, U., Magnusson, K.P., Walters, G.B., Palsdottir, E., Jonsdottir, T., Gudmundsdottir, T., Gylfason, A., Saemundsdottir, J., Wilensky, R.L., Reilly, M.P., Rader, D.J., Bagger, Y., Christiansen, C., Gudnason, V., Sigurdsson, G., Thorsteinsdottir, U., Gulcher, J.R., Kong, A., Stefansson, K. Nat. Genet. (2006) [Pubmed]
  7. Crystal Structure of a beta-Catenin/BCL9/Tcf4 Complex. Sampietro, J., Dahlberg, C.L., Cho, U.S., Hinds, T.R., Kimelman, D., Xu, W. Mol. Cell (2006) [Pubmed]
  8. Involvement of Splicing Factor-1 in beta-Catenin/T-Cell Factor-4-Mediated Gene Transactivation and Pre-mRNA Splicing. Shitashige, M., Naishiro, Y., Idogawa, M., Honda, K., Ono, M., Hirohashi, S., Yamada, T. Gastroenterology (2007) [Pubmed]
  9. Tcf4 can specifically recognize beta-catenin using alternative conformations. Graham, T.A., Ferkey, D.M., Mao, F., Kimelman, D., Xu, W. Nat. Struct. Biol. (2001) [Pubmed]
  10. Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3. Duval, A., Busson-Leconiat, M., Berger, R., Hamelin, R. Cytogenet. Cell Genet. (2000) [Pubmed]
  11. Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women. Humphries, S.E., Gable, D., Cooper, J.A., Ireland, H., Stephens, J.W., Hurel, S.J., Li, K.W., Palmen, J., Miller, M.A., Cappuccio, F.P., Elkeles, R., Godsland, I., Miller, G.J., Talmud, P.J. J. Mol. Med. (2006) [Pubmed]
  12. Repressor roles for TCF-4 and Sfrp1 in Wnt signaling in breast cancer. Shulewitz, M., Soloviev, I., Wu, T., Koeppen, H., Polakis, P., Sakanaka, C. Oncogene (2006) [Pubmed]
  13. Transcription Factor TCF7L2 Genetic Study in the French Population: Expression in Human {beta}-Cells and Adipose Tissue and Strong Association With Type 2 Diabetes. Cauchi, S., Meyre, D., Dina, C., Choquet, H., Samson, C., Gallina, S., Balkau, B., Charpentier, G., Pattou, F., Stetsyuk, V., Scharfmann, R., Staels, B., Fr??hbeck, G., Froguel, P. Diabetes (2006) [Pubmed]
  14. BMPs restrict the position of premuscle masses in the limb buds by influencing Tcf4 expression. Bonafede, A., K??hler, T., Rodriguez-Niedenf??hr, M., Brand-Saberi, B. Dev. Biol. (2006) [Pubmed]
  15. Human immunodeficiency virus type 1 Tat prevents dephosphorylation of Sp1 by TCF-4 in astrocytes. Rossi, A., Mukerjee, R., Ferrante, P., Khalili, K., Amini, S., Sawaya, B.E. J. Gen. Virol. (2006) [Pubmed]
  16. Haplotypes of Transcription Factor 7-Like 2 (TCF7L2) Gene and Its Upstream Region Are Associated With Type 2 Diabetes and Age of Onset in Mexican Americans. Lehman, D.M., Hunt, K.J., Leach, R.J., Hamlington, J., Arya, R., Abboud, H.E., Duggirala, R., Blangero, J., Göring, H.H., Stern, M.P. Diabetes (2007) [Pubmed]
  17. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. Lyssenko, V., Lupi, R., Marchetti, P., Del Guerra, S., Orho-Melander, M., Almgren, P., Sjögren, M., Ling, C., Eriksson, K.F., Lethagen, A.L., Mancarella, R., Berglund, G., Tuomi, T., Nilsson, P., Del Prato, S., Groop, L. J. Clin. Invest. (2007) [Pubmed]
  18. TCF7L2 gene polymorphisms confer an increased risk for early impairment of glucose metabolism and increased height in obese children. Körner, A., Berndt, J., Stumvoll, M., Kiess, W., Kovacs, P. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  19. Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Schäfer, S.A., Tschritter, O., Machicao, F., Thamer, C., Stefan, N., Gallwitz, B., Holst, J.J., Dekker, J.M., 't Hart, L.M., t'Hart, L.M., Nijpels, G., van Haeften, T.W., Häring, H.U., Fritsche, A. Diabetologia (2007) [Pubmed]
  20. Effects of the diabetes linked TCF7L2 polymorphism in a representative older population. Melzer, D., Murray, A., Hurst, A.J., Weedon, M.N., Bandinelli, S., Corsi, A.M., Ferrucci, L., Paolisso, G., Guralnik, J.M., Frayling, T.M. BMC medicine (2006) [Pubmed]
  21. Combining information from common type 2 diabetes risk polymorphisms improves disease prediction. Weedon, M.N., McCarthy, M.I., Hitman, G., Walker, M., Groves, C.J., Zeggini, E., Rayner, N.W., Shields, B., Owen, K.R., Hattersley, A.T., Frayling, T.M. PLoS Med. (2006) [Pubmed]
  22. Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Scott, L.J., Bonnycastle, L.L., Willer, C.J., Sprau, A.G., Jackson, A.U., Narisu, N., Duren, W.L., Chines, P.S., Stringham, H.M., Erdos, M.R., Valle, T.T., Tuomilehto, J., Bergman, R.N., Mohlke, K.L., Collins, F.S., Boehnke, M. Diabetes (2006) [Pubmed]
  23. Physiological and functional interactions between Tcf4 and Daxx in colon cancer cells. Tzeng, S.L., Cheng, Y.W., Li, C.H., Lin, Y.S., Hsu, H.C., Kang, J.J. J. Biol. Chem. (2006) [Pubmed]
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