TCF7L2

Transcription factor 7-like 2 (T-cell specific, HMG-box) also known as TCF7L2 or TCF4 is a is_associated_with::protein acting as a is_associated_with::transcription factor. In humans this protein is encoded by the TCF7L2 is_associated_with::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 is_associated_with::type 2 diabetes, as well as is_associated_with::gestational diabetes.



Function
TCF7L2 is a is_associated_with::transcription factor influencing the transcription of several is_associated_with::genes thereby exerting a large variety of functions within the cell. It is a member of the is_associated_with::Wnt signaling pathway. Stimulation of the pathway leads to the association of β-catenin with is_associated_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 is_associated_with::single nucleotide polymorphisms are associated with is_associated_with::type 2 diabetes. In European populations it was found to be a major determinant of type 2 risk.

A is_associated_with::frameshift mutation of TCF7L2 is implicated in is_associated_with::colorectal cancer. Variants of the gene are most likely involved in many other cancer types.

Model organisms
is_associated_with::Model organisms have been used in the study of TCF7L2 function. A conditional is_associated_with::knockout mouse line called Tcf7l2tm1a(EUCOMM)Wtsi was generated at the is_associated_with::Wellcome Trust Sanger Institute. Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping

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Nomenclature
While TCF4 is sometimes used as an alias symbol for TCF7L2, it is also the symbol officially approved by the is_associated_with::HUGO Gene Nomenclature Committee for the transcription factor 4 gene.