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 TCF7L2gene. 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.
Structure of complex between TCF7L2 (orange), β-catenin (red), and BCL9 (brown).
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.
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