TCF7L2

Transcription factor 7-like 2 (T-cell specific, HMG-box)
PDB rendering based on 1jdh.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1JDH, 1JPW, 2GL7
Identifiers
Symbols	TCF7L2 ; TCF-4; TCF4
External IDs	OMIM: 602228 MGI: 1202879 HomoloGene: 7564 GeneCards: TCF7L2 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • RNA polymerase II repressing transcription factor binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • protein binding • beta-catenin binding • transcription factor binding • protein kinase binding • nuclear hormone receptor binding • sequence-specific DNA binding • transcription regulatory region DNA binding • gamma-catenin binding • armadillo repeat domain binding Cellular component • nuclear chromatin • nucleus • nucleoplasm • transcription factor complex • cytoplasm • PML body • protein-DNA complex • beta-catenin-TCF7L2 complex Biological process • negative regulation of transcription from RNA polymerase II promoter • blood vessel development • cellular glucose homeostasis • glycogen metabolic process • glucose metabolic process • transcription, DNA-templated • regulation of transcription from RNA polymerase II promoter • cell cycle arrest • cell proliferation • cellular response to starvation • response to glucose • post-embryonic development • positive regulation of triglyceride biosynthetic process • positive regulation of heparan sulfate proteoglycan biosynthetic process • oligodendrocyte development • neural tube development • pituitary gland development • bone mineralization • negative regulation of BMP signaling pathway • embryonic genitalia morphogenesis • pancreas development • regulation of myelination • positive regulation of insulin secretion • positive regulation of protein binding • secretory granule localization • regulation of hormone metabolic process • somatic stem cell maintenance • multicellular organism growth • catenin import into nucleus • regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter • negative regulation of fibroblast growth factor receptor signaling pathway • odontogenesis of dentin-containing tooth • glucose homeostasis • positive regulation of apoptotic process • negative regulation of sequence-specific DNA binding transcription factor activity • maintenance of DNA repeat elements • skin development • canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition • fat cell differentiation • negative regulation of fat cell differentiation • positive regulation of gluconeogenesis • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • negative regulation of organ growth • positive regulation of protein export from nucleus • embryonic digestive tract morphogenesis • embryonic hindgut morphogenesis • myoblast fate commitment • regulation of skeletal muscle tissue development • regulation of smooth muscle cell proliferation • generation of neurons • regulation of oligodendrocyte differentiation • positive regulation of epithelial cell proliferation • positive regulation of protein kinase B signaling • canonical Wnt signaling pathway • face morphogenesis • regulation of insulin secretion involved in cellular response to glucose stimulus • negative regulation of canonical Wnt signaling pathway • insulin metabolic process • negative regulation of type B pancreatic cell apoptotic process • negative regulation of extrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6934	21416
Ensembl	ENSG00000148737	ENSMUSG00000024985
UniProt	Q9NQB0	Q924A0
RefSeq (mRNA)	NM_001146274	NM_001142918
RefSeq (protein)	NP_001139746	NP_001136390
Location (UCSC)	Chr 10: 112.95 – 113.17 Mb	Chr 19: 55.74 – 55.93 Mb
PubMed search	[1]	[2]

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.

File:TCF7L2 beta-catenin BCL9.png

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

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 Tcf7l2^{tm1a(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

Tcf7l2 knockout mouse phenotype

Characteristic	Phenotype
All data available at.
Insulin	Normal
Homozygous viability at P14	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

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.

See also

• TCF/LEF family

External links

• TCF7L2 here called TCF4 features on this Wnt pathway web site: Wnt signalling molecules TCFs
• Structure determination of TCF7L2: PDB entry 2GL7 and related publication on PubMed
• PubMed GeneRIFs (summaries of related scientific publications) - [3]
• Weizmann Institute GeneCard for TCF7L2