Species Human Entrez 6934 | Human Mouse Ensembl ENSG00000148737 | |
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Aliases TCF7L2, TCF-4, TCF4, transcription factor 7 like 2 External IDs OMIM: 602228 MGI: 1202879 HomoloGene: 7564 GeneCards: TCF7L2 | ||
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. The single nucleotide polymorphism (SNP) within the TCF7L2 gene, rs7903146, is, to date, the most significant genetic marker associated with Type 2 diabetes mellitus (T2DM) risk. SNPs in this gene are linked to higher risk to develop type 2 diabetes, as well as gestational diabetes.
Contents
Function
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, which in turn results in the activation of Wnt target genes, specifically repressing proglucagon synthesis in enteroendocrine cells.
Clinical significance
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.
A frameshift mutation of TCF7L2 is implicated in colorectal cancer. Variants of the gene are most likely involved in many other cancer types.
Model organisms
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. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping
Nomenclature
While TCF4 is sometimes misleadingly 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.