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 TCF family that can form a bipartite transcription factor (β-catenin/TCF) alongside β-catenin. Bipartite transcription factors can have large effects on the Wnt signalling pathway. Stimulation of the Wnt signaling 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. The activation of the Wnt target genes specifically represses proglucagon synthesis in enteroendocrine cells. The repression of TCF7L2 using HMG-box repressor (HBP1) inhibits Wnt signalling. Therefore, TCF7L2 is an effector in the Wnt signalling pathway. TCF7L2's role in glucose metabolism is expressed in many tissues such as gut, brain, liver, and skeletal muscle. However, TCF7L2 does not directly regulate glucose metabolism in β-cells, but regulates glucose metabolism in pancreatic and liver tissues. That said, TCF7L2 directly regulates the expression of multiple transcription factors, axon guidance cues, cell adhesion molecules and ion channels in the thalamus.
The TCF7L2 gene encoding the TCF7L2 transcription factor, exhibits multiple functions through its polymorphisms and thus, is known as a pleiotropic gene. Type 2 diabetes T2DM susceptibility is exhibited in carriers of TCF7L2 rs7903146C>T and rs290481T>C polymorphisms. TCF7L2 rs290481T>C polymorphism, however, has shown no significant correlation to the susceptibility to gestational diabetes mellitus (GDM) in a Chinese Han population, whereas the T alleles of rs7903146 and rs1799884 increase susceptibility to GDM in the Chinese Han population. The difference in effects of the different polymorphisms of the gene indicate that the gene is indeed pleiotropic.