[22] That said, TCF7L2 directly regulates the expression of multiple transcription factors, axon guidance cues, cell adhesion molecules and ion channels in the thalamus.

[27] TCF7L2 is primarily expressed in brain (mainly in the diencephalon, including especially high in the thalamus[23][28][29]), liver, intestine and fat cells.

Studies conducted by Ravindranath Duggirala and Michael Stern at The University of Texas Health Science Center at San Antonio were the first to identify strong linkage for type 2 diabetes at a region on Chromosome 10 in Mexican Americans [31] This signal was later refined by Struan Grant and colleagues at DeCODE genetics and isolated to the TCF7L2 gene.

[9] TCF7L2 modulates pancreatic islet β-cell function strongly implicating its significant association with GDM risk.

[37] Single nucleotide polymorphisms (SNPs) in TCF7L2 gene have shown an increase in susceptibility to schizophrenia in Arab, European and Chinese Han populations.

[15][16] The mechanism behind TCF7L2's involvement in the emergence of neurodevelopmental disorders is not fully understood, as there have been few studies characterizing its role in brain development in detail.

It was shown that during embryogenesis TCF7L2 is involved in the development of fish-specific habenula asymmetry in Danio rerio,[39][40] and that the dominant negative TCF7L2 isoform influences cephalic separation in the embryo by inhibiting the posteriorizing effect of the Wnt pathway.

[43] More recently it was shown that TCF7L2 plays a crucial role in both the embryonic development and postnatal maturation of the thalamus through direct and indirect regulation of many genes previously reported to be important for both processes.

[23] In the early postnaral period TCF7L2 starts to regulate the expression of many genes necessary for the acquisition of characteristic excitability patterns in the thalamus, mainly ion channels, neurotransmitters and their receptors and synaptic vescicle proteins (e.g. Cacna1g, Kcnc2, Slc17a7, Grin2b), and an early postnatal knockout of Tcf7l2 in mouse thalamus leads to significant reduction in the number and frequency of action potentials generated by the thalamocortical neurons.

[28] Abnormalities in the anatomy of the thalamus and the activity of its connections to the cerebral cortex are frequently detected in patients with schizophrenia [44][45][46][47] and autism.

A conditional knockout mouse line called Tcf7l2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.

Variations of the protein encoding gene are found in rats, zebra fish, drosophila, and budding yeast.