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FLASH GENE

Symbol

TCF7L2

contributors: mct/pgu - updated : 27-12-2018

HGNC name	transcription factor 7-like 2 (T-cell specific, HMG-box)
HGNC id	11641

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine parathyroid       highly Reproductive female system breast mammary gland   highly Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a CTNNB binding domain
	a HMG box DNA-binding domain
	two CtBP binding motifs only present in the long size C terminal isoforms

HOMOLOGY

Homologene

FAMILY

TCF/LEF family

CATEGORY

regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm,nuclear bodies,PML
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	segment polarity protein, acting as a transcriptional activator
	high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis
	may play a role in both glucose homeostasis and adipogenesis (have an inhibitory role of adipogenesis)
	controls insulin gene expression and insulin secretion in mature pancreatic beta-cells
	may be having pleiotropic tissue-specific roles and alterations in one or more of these functions could lead to T2 Diabetes
	plays a key role in TGFB-mediated activation of the PMEPA1 gene
	important transcription factor in WNT pathway, playing critical roles in oligodendrocyte development
	key role for TCF7L2 in myelination/remyelination processes via a tightly controlled activation of WNT/CTNNB1 pathway and the interaction with OLIG2
	likely a crucial role of TCF7L2 in hepatic glucose metabolism
	TCF7L2 directly activates metabolic genes
	WNT/TCF7L2-dependent signaling could play a role in extravillous trophoblasts (EVTs) differentiation promoting motility and expression of promigratory genes
	is a master regulator of insulin production and processing
	is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries
	plays a cell autonomous role in the control of beta cell function and mass, serving as an important regulator of gene expression and islet cell coordination
	plays key roles in glucose metabolism through actions beyond pancreatic beta cells, but with functionally opposing cell-type specific effects on the maintenance of balanced glucose metabolism
	TCF7L2, a CTNNB1 transcriptional partner, is required for oligodendrocyte differentiation

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

Wnt (APC/beta catenin/TCF pathway)

a component

INTERACTION

DNA

RNA

small molecule

protein	MAD2L2-binding protein (interaction abolished the DNA binding ability of TCF7L2)
	AES interacts with T-cell factor 4 (TCF7L2) and downregulates WNT signaling
	tissue-specific differences in the regulation of WWC1 gene expression involve transcription factor TCF7L2 and a complex alternative promoter system
	TCF7L2 transcriptionally regulated 29 genes related to glucose metabolism, including glucose-6-phosphatase
	during oligodendrocyte maturation, TCF7L2 recruits and cooperates with SOX10 to promote myelination
	stage-specific co-regulators ZBTB33 and SOX10 sequentially interact with TCF7L2 to coordinate the switch at the transitions of differentiation initiation and maturation during oligodendrocyte development
	transcriptional co-activator of CTNNB1
	FRMD5 is a novel direct target of the CTNNB/TCF7L2 complex

cell & other

REGULATION

inhibited by

insulin

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       in gastrointestinal tumor tumoral fusion       with VTI1A in colorectal cancers constitutional     --over   attenuated insulin secretion, consistent with the extra TCF7L2 translocating CTNNB1 from the plasma membrane pool to the nucleus constitutional     --over   may contribute to cartilage degeneration in Osteoarthritis by augmenting NFKB1 signaling constitutional       gain of function is associated with BCL2 repression promoting vascular smooth muscle cell apoptosis, a key driver of TAA disease constitutional     --over   may result in enhanced apoptosis of vascular smooth muscle cells—a likely mechanism of action of TAA-associated variants in TCF7L2

Susceptibility

to type 2 gestational diabetes with alteration of the birth weight to polycystic ovary syndrome to type 2 diabetes (T2D) to Thoracic aortic aneurysm (TAA)

Variant & Polymorphism SNP	increasing thre risk of type 2 diabetes and altering birth weight
	polymorphisms that may confer an increased risk for early impairment of glucose metabolism in obese children
	rs11196236 and rs11196229 increasing the risk of polycystic ovary syndrome
	rs7903146 and rs12255372, located within introns 3 and 4 of the gene and most strongly associated with T2D
	TCF7L2 rs7903146 polymorphism was associated with susceptibility to gestational diabetes mellitus (GDM)
	variants within the third intron of TCF7L2 significantly associated with TAA

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS