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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TCF7L2 Gene

protein-coding GIFtS: 68
GCID: GC10P114710

transcription factor 7-like 2 (T-cell specific, HMG-box)

(Previous symbol: TCF4)

Explore 71 diseases affiliated with
TCF7L2 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Transcription Factor 7-Like 2 (T-Cell Specific, HMG-Box)¹ ²		T-Cell Factor-4 Variant E²
TCF4¹ ² ³ ⁵		T-Cell Factor-4 Variant F²
TCF-4¹ ² ³		T-Cell Factor-4 Variant G²
HTCF-4¹		T-Cell Factor-4 Variant H²
HMG Box Transcription Factor 4² ³		T-Cell Factor-4 Variant I²
T-Cell Factor 4² ³		T-Cell Factor-4 Variant J²
T-Cell-Specific Transcription Factor 4² ³		T-Cell Factor-4 Variant K²
T-Cell Factor-4 Variant A²		T-Cell Factor-4 Variant L²
T-Cell Factor-4 Variant B²		T-Cell Factor-4 Variant M²
T-Cell Factor-4 Variant C²		T-Cell Factor-4 Variant X2²
T-Cell Factor-4 Variant D²		Transcription Factor 7-Like 2²

External Ids:	HGNC: 11641¹	Entrez Gene: 6934²	Ensembl: ENSG00000148737⁷	OMIM: 602228⁵	UniProtKB: Q9NQB0³

Export aliases for TCF7L2 gene to outside databases

Previous GC identifers: GC10P113605 GC10P113943 GC10P114841 GC10P114374 GC10P114700 GC10P108337

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TCF7L2:

This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt

signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are

associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms

have been found for this gene.(provided by RefSeq, Oct 2010)

UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0

Function: Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a

sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates

transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1,

TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative

mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of

the small intestine

Gene Wiki entry for TCF7L2

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000010.10 NC_018921.1 NT_030059.13

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TCF7L2 gene promoter:
N-Myc PPAR-gamma1 STAT3 PPAR-gamma2 AP-2alpha HNF-4alpha1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): TCF7L2 promoter sequence

Search SABiosciences Chromatin IP Primers for TCF7L2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TCF7L2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 10q25.3 Ensembl cytogenetic band: 10q25.2 HGNC cytogenetic band: 10q25.3

TCF7L2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TCF7L2 gene location

GeneLoc information about chromosome 10 GeneLoc Exon Structure

GeneLoc location for GC10P114710: view genomic region (about GC identifiers)

Start:	114,710,009 bp from pter	End:	114,927,437 bp from pter
Size:	217,429 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0 (See protein sequence)

Recommended Name: Transcription factor 7-like 2

Size: 619 amino acids; 67919 Da

Subunit: Interacts with TGFB1I1 (By similarity). Interacts with CTNNB1 (via the armadillo repeat); forms stable

transcription complex. Interacts with EP300. Interacts with NLK. Interacts with CCDC85B (probably through the HMG

box); prevents interaction with CTNNB1. Interacts with TNIK. Interacts with MAD2L2; prevents TCF7L2/TCF4 binding to

promZIPK/DAPK3oters, negatively modulating its transcriptional activity. Interacts with ZIPK/DAPK3. Interacts with

XIAP/BIRC4 and TLE3. Interacts with DDIT3/CHOP

Subcellular location: Nucleus, PML body. Note=Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML

(promyelocytic leukemia) nuclear bodies

Developmental stage: Highly expressed in crypt regions and barely detectable in villi in epithelium from fetal small

intestine at week 16. At week 22 expression in villi had increased strongly

3 PDB 3D structures from and Proteopedia for TCF7L2:

1JDH (3D)

1JPW (3D)

2GL7 (3D)

Secondary accessions: F8W742 F8W7T5 O00185 Q9NQB1 Q9NQB2 Q9NQB3 Q9NQB4 Q9NQB5 Q9NQB6 Q9NQB7 Q9ULC2

Alternative splicing: 12 isoforms: Q9NQB0-1 Q9NQB0-2 Q9NQB0-3 Q9NQB0-4 Q9NQB0-5 Q9NQB0-6 Q9NQB0-7 Q9NQB0-8

Q9NQB0-9 Q9NQB0-10 Q9NQB0-11 Q9NQB0-12

Explore the universe of human proteins at neXtProt for TCF7L2: NX_Q9NQB0

Post-translational modifications:

In vitro, phosphorylated by TNIK¹

Phosphorylated at Thr-201 and/or Thr-212 by NLK. Phosphorylation by NLK at these sites inhibits DNA-binding by

TCF7L2/TCF4, thereby preventing transcriptional activation of target genes of the canonical Wnt/beta-catenin signaling

pathway¹

Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylation is enhanced by SENP2.

Sumoylation/desumoylation regulates TCF7L2/TCF4 transcription activity in the Wnt/beta-catenin signaling pathway

without altering interaction with CTNNB1 nor binding to DNA¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q9NQB0

TCF7L2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (13 alternative transcripts):

NP_001139746.1 NP_001139755.1 NP_001139756.1 NP_001139757.1 NP_001139758.1 NP_001185454.1 NP_001185455.1 NP_001185456.1

NP_001185457.1 NP_001185458.1 NP_001185459.1 NP_001185460.1 NP_110383.2

ENSEMBL proteins:

ENSP00000358404 ENSP00000298692 ENSP00000358402 ENSP00000345640 ENSP00000358396

ENSP00000277945 ENSP00000358393 ENSP00000435694 ENSP00000348274 ENSP00000440547

ENSP00000444972 ENSP00000446238 ENSP00000347949 ENSP00000446172 ENSP00000344823

ENSP00000443626 ENSP00000443883

Human Recombinant Protein Products:

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	Novus Biologicals TCF7L2 Proteins Novus Biologicals TCF7L2 Lysates
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	Browse ProSpec Recombinant Proteins
	Uscn Proteins for TCF7L2

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000790	nuclear chromatin	IDA	19443654
GO:0005634	nucleus	IDA	19386626
GO:0005654	nucleoplasm	IDA	19168596
GO:0005667	transcription factor complex	IBA	--
GO:0016605	PML body	IEA	--

TCF7L2 for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for TCF7L2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TCF7L2 for domains About GeneDecksing

3 InterPro domains/families:

IPR009071 HMG_superfamily

IPR024940 TCF/LEF

IPR013558 CTNNB1-bd_N

Graphical View of Domain Structure for InterPro Entry Q9NQB0

ProtoNet protein and cluster: Q9NQB0

1 Blocks protein family: IPB013558 CTNNB1 binding

UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0

Domain: The promoter-specific activation domain interacts with the transcriptional coactivator EP300

Similarity: Belongs to the TCF/LEF family

Similarity: Contains 1 HMG box DNA-binding domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0

Function: Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a

sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates

transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1,

TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative

mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of

the small intestine

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		hsa-miR-411* hsa-miR-218-1* hsa-miR-1258 hsa-miR-485-3p hsa-miR-938 hsa-miR-877* hsa-miR-3161 hsa-miR-629

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Gene Editing
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TCF7L2

Gene Ontology (GO): 5/13 molecular function terms (GO ID links to tree view) (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	IDA	19443654
GO:0001103	RNA polymerase II repressing transcription factor binding	IPI	19443654
GO:0003682	chromatin binding	IBA	--
GO:0003700	sequence-specific DNA binding transcription factor activity	IDA	9727977
GO:0005515	protein binding	IPI	17875931

TCF7L2 for ontologies About GeneDecksing

3 GenomeRNAi human phenotypes for TCF7L2:

Increased S DNA content

Increased cell death in breast

Increased gamma-H2AX phosphory

Animal Models:
Mouse knock-outs for TCF7L2: Tcf7l2^tm1Cle Tcf7l2^tm2.2Mrc
14 MGI mutant phenotypes (inferred from 12 alleles) (MGI details for Tcf7l2):

adipose tissue	behavior/neurological	cellular	craniofacial	digestive/alimentary
endocrine/exocrine gland	growth/size	homeostasis/metabolism	integument	liver/biliary system
mortality/aging	muscle	nervous system	tumorigenesis

TCF7L2 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/23 super-pathways (see all 23) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Endometrial cancer

Endometrial cancer	1.00	Colorectal cancer	0.42
Signal transduction_PTEN pathway	0.45	Acute myeloid leukemia	0.39
Signal transduction PTEN pathway	0.45

Wnt Signaling Pathway

	Wnt Signaling Pathway and Pluripotency	0.55			Wnt signaling pathway	0.30
	Wnt Signaling Pathway	0.33

Cell adhesion Tight junctions

Cell adhesion Tight junctions

1.00

Cell adhesion_Tight junctions

0.99

Development_A3 receptor signaling

Development A3 receptor signaling

1.00

Development_A3 receptor signaling

1.00

Human Embryonic Stem Cell Pluripotency

Human Embryonic Stem Cell Pluripotency

1.00

Factors Promoting Cardiogenesis in Vertebrates

0.50

Pathway sources
See GeneCards unified pathways
Show all pathways

5/6 EMD Millipore Pathways for TCF7L2 (see all 6)

	Cytoskeleton remodeling Integrin outside-in signaling
	Cell adhesion Tight junctions
	Signal transduction PTEN pathway
	Development Endothelin-1/EDNRA signaling
	Development A3 receptor signaling

1 R&D Systems Pathway for TCF7L2

Wnt Signaling Pathway

5/7 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for TCF7L2 (see all 7)

	MAPK Signaling
	ILK Signaling
	Factors Promoting Cardiogenesis in Vertebrates
	Human Embryonic Stem Cell Pluripotency
	JNK Pathway

1 Cell Signaling Technology (CST) Pathway for TCF7L2

Wnt / Hedgehog / Notch

5/8 GeneGo (Thomson Reuters) Pathways for TCF7L2 (see all 8)

	Cytoskeleton remodeling Integrin outside-in signaling
	Development A2B receptor- action via G-protein alpha s
	Development VEGF signaling via VEGFR2 - generic cascades
	Development A3 receptor signaling
	Development HGF signaling pathway

4 BioSystems Pathways for TCF7L2

	Wnt Signaling Pathway and Pluripotency
	Arrhythmogenic right ventricular cardiomyopathy
	Id Signaling Pathway
	Regulation of Wnt-mediated beta catenin signaling and target gene transcription

5/11 Kegg Pathways (Kegg details for TCF7L2) (see all 11):

	Wnt signaling pathway
	Adherens junction
	Melanogenesis
	Pathways in cancer
	Colorectal cancer

TCF7L2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TCF7L2

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/82 Interacting proteins for TCF7L2 (Q9NQB0^{1, 2, 3} ENSP00000358404⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 82)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
HIC1	Q14526²^,³, ENSP00000314080⁴	MINT-2730845 MINT-2730694 MINT-2730765 MINT-2730819 MINT-2730877 MINT-2730798 I2D: score=2 STRING: ENSP00000314080
TNIK	Q9UKE5²^,³, ENSP00000399511⁴	MINT-7952375 MINT-7952429 MINT-7952386 I2D: score=1 STRING: ENSP00000399511
JUP	P14923¹^,³, ENSP00000311113⁴	EBI-924724,EBI-744449 I2D: score=2 STRING: ENSP00000311113
XRCC6	P12956¹^,³, ENSP00000352257⁴	EBI-924724,EBI-2843064 I2D: score=1 STRING: ENSP00000352257
CTNNB1	P35222¹^,²^,³, ENSP00000344456⁴	EBI-924724,EBI-491549 MINT-2730974 MINT-7952375 MINT-1779698 MINT-7952386 I2D: score=8 STRING: ENSP00000344456

About this table

Gene Ontology (GO): 5/53 biological process terms (GO ID links to tree view) (see all 53): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	IDA	12799378
GO:0001568	blood vessel development	IMP	15578569
GO:0006351	transcription, DNA-dependent	IEA	--
GO:0006357	regulation of transcription from RNA polymerase II promoter	IDA	9727977
GO:0007050	cell cycle arrest	IMP	12408868

TCF7L2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TCF7L2 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for TCF7L2
10/14 Novoseek chemical compound relationships for TCF7L2 gene (see all 14) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
proglucagon	66.6	1	15525634 (1)
mononucleotide	53.9	4	18755497 (2), 11746989 (1), 19787250 (1)
glycogen	50.7	4	20442281 (1), 15525634 (1), 15940626 (1), 19818782 (1)
glucose	47	13	17697858 (1), 19105201 (1), 16415884 (1), 17437080 (1) (see all 11)
sulindac	41.5	3	11751639 (1), 14610217 (1)
lithium chloride	38.4	1	19679347 (1)
ly294002	33.4	4	19190323 (1)
phosphatidylinositol	11.7	4	19190323 (1)
nitric oxide	5.06	1	20096072 (1)
butyrate	0.698	2	11774242 (1)

2 PharmGKB related drug/compound annotations for TCF7L2 gene

Drug/compound	PharmGKB Annotation
"sulfonamides, urea derivatives"	CA
repaglinide	CA

About this table

Search CenterWatch for drugs/clinical trials and news about TCF7L2 / TF7L2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TCF7L2 gene (13 alternative transcripts):

NM_001146274.1 NM_001146283.1 NM_001146284.1 NM_001146285.1 NM_001146286.1 NM_001198525.1 NM_001198526.1 NM_001198527.1

NM_001198528.1 NM_001198529.1 NM_001198530.1 NM_001198531.1 NM_030756.4

Unigene Cluster for TCF7L2:

Transcription factor 7-like 2 (T-cell specific, HMG-box)

Hs.593995 [show with all ESTs]

Unigene Representative Sequence: NM_001198525

18/22 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 22):

ENST00000369397(uc010qrs.2 uc010qrv.2 uc010qrw.2 uc010qrx.2)

ENST00000349937 ENST00000369395 ENST00000346198 ENST00000369389 ENST00000277945

ENST00000369386 ENST00000466338 ENST00000470254 ENST00000480888 ENST00000471569

ENST00000476887 ENST00000494353 ENST00000355995(uc021pyg.1 uc021pyi.1 uc010qrp.2 uc010qrq.2 uc001lac.4)

ENST00000545257(uc001lah.3 uc010qrt.2) ENST00000543371(uc001lae.4 uc021pyk.1 uc021pyn.1 uc010qrl.2)

ENST00000536810(uc001laf.4) ENST00000355717(uc001lag.4 uc010qrr.2 uc010qru.2)

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		hsa-miR-411* hsa-miR-218-1* hsa-miR-1258 hsa-miR-485-3p hsa-miR-938 hsa-miR-877* hsa-miR-3161 hsa-miR-629

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Additional cDNA sequence:

AB034691.1 AB440195.1 AB451266.1 AK054578.1 AK074705.1 AK225809.1 AK296305.1 AK299295.1

AK301483.1 AK303684.1 AK315243.1 AK316111.1 BC032656.1 BX648364.1 CR536574.1 FJ010164.1

FJ010165.1 FJ010166.1 FJ010167.1 FJ010168.1 FJ010169.1 FJ010170.1 FJ010171.1 FJ010172.1

FJ010173.1 FJ010174.1 HM352838.1 HM352839.1 HM352840.1 HM352841.1 HM352842.1 HM352843.1

HM352844.1 HM352845.1 HM352846.1 HM352847.1 HM352848.1 HM352849.1 HM352850.1 HM352851.1

Y11306.2

22 DOTS entries:

DT.100717951 DT.100814194 DT.95371069 DT.95371070 DT.121279537 DT.121279368 DT.110441 DT.97859220

DT.121279438 DT.121279575 DT.91742749 DT.100814193 DT.40266758 DT.75100728 DT.121279380 DT.121279454

DT.121279480 DT.70101434 DT.99954951 DT.75136202 DT.91856101 DT.99984552

24/176 AceView cDNA sequences (see all 176):

AW628584 BM671072 AA812256 BM142562 AI868258 AI084440 BM702280 AU120697

BM701919 AA609985 BM679756 AU118429 AW467057 AA045265 BM681576 AI933235

CR536574 AI250908 CN483425 AA621494 BU617649 T54154 AI168772 BU195676

GeneLoc Exon Structure

5/10 Alternative Splicing Database (ASD) splice patterns (SP) for TCF7L2 (see all 10) About this scheme

ExUns:	1a	·	1b	·	1c	^	2	^	3a	·	3b	^	4	^	5	^	6	^	7	^	8	^	9	^	10	^	11a	·	11b	·	11c	^	12a	·	12b	·	12c	^	13a	·	13b	·	13c	·	13d	^	14	^	15	^	16a	·
SP1:									-				-				-		-		-		-
SP2:									-								-		-		-		-
SP3:									-				-				-		-		-		-								-
SP4:																					-		-
SP5:																							-

ExUns:	16b	^	17	^	18	^	19	^	20a	·	20b	·	20c	·	20d	·	20e
SP1:							-
SP2:			-		-
SP3:					-		-
SP4:
SP5:

ECgene alternative splicing isoforms for TCF7L2

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TCF7L2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: ATTCTACCAA

About this image

TCF7L2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

8 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Reproductive System

Early Gonad

Testis Somatic Cells

Testis

Bone

Brain

Brain

Diencephalic Ventricular Zone

Neural Tube

Mesencephalic Ventricular Zone

Neural Tube

Metencephalon

Neural Tube

Telencephalon

Neural Tube

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

Extraembryonic endoderm-like cells (Generation of extrae...)

See TCF7L2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TCF7L2

SOURCE GeneReport for Unigene cluster: Hs.593995

UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0

Tissue specificity: Detected in epithelium from small intestine, with the highest expression at the top of the crypts

and a gradient of expression from crypt to villus. Detected in colon epithelium and colon cancer, and in epithelium

from mammary gland and carcinomas derived therefrom

SABiosciences Expression via Pathway-Focused PCR Arrays including TCF7L2 (see all 6):

Parkinson's Disease in human mouse rat

Stem Cell Transcription Factors in human mouse rat

WNT Signaling Targets in human mouse rat

Stem Cell Signaling in human mouse rat

Transcription Factors in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for TCF7L2 gene from 6/19 species (see all 19) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	TCF7L2¹	transcription factor 7-like 2 (T-cell specific, HMG-box)	85.88(n) 94.27(a)		395508 NM_001206510.1 NP_001193439.1
lizard (Anolis carolinensis)	Reptilia	-- --	--	94(a) 84(a)	1 ↔ many 1 ↔ many	AAWZ02039818(1550-4308) GL343204.1(1238381-1270708)
African clawed frog (Xenopus laevis)	Amphibia	Xl.11987²	Xenopus laevis T-cell factor 4 mRNA, complete cds	78.33(n)		AF207708.1
zebrafish (Danio rerio)	Actinopterygii	tcf4²	transcription factor tcf4	81.31(n)		30510 AF507957.1
fruit fly (Drosophila melanogaster)	Insecta	pan^{1 , 3}	heart development transcription factor³ pangolin¹	38(a)³ 48.02(n)¹ 45.7(a)¹		43769¹ NM_001014685.2¹ NP_001014685.1¹
worm (Caenorhabditis elegans)	Secernentea	pop-1⁶	Protein pop-1	27(a)	1 → many	I(2823470-2830295)

ENSEMBL Gene Tree for TCF7L2 (if available)
TreeFam Gene Tree for TCF7L2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for TCF7L2 gene

LEF1² TCF7L1² TCF7²

7 SIMAP similar genes for TCF7L2 using alignment to 25 protein entries: TF7L2_HUMAN (see all proteins):

DKFZp586H0919 TCF7L1 TCF7 CIC LEF1 soxB

SRY

TCF7L2 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 10 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs117598756^1,2	C,F,	--	108335574(+)	`TTCACT/CTGGTG`	13	--	us2k¹		1		NA	120
rs77399581^1,2	F,	--	108335584(+)	`GTCTTG/AAAATA`	13	--	us2k¹		1		NA	120
rs56408190^1,2	C	--	108336645(+)	`CAGTTT/AAAAAA`	13	--	us2k¹		1		WA	2
rs79046415^1,2	F,	--	108336839(+)	`GAGGGG/AGGCCT`	13	--	us2k¹		2		CSA	4
rs77825067^1,2		--	108336933(+)	`GGTTGA/TTCTTT`	13	--	us2k¹		2		CSA WA	120
rs77172590^1,2	C,	--	108337519(+)	`TCTCCG/TCTCCC`	13	--	ut5¹		3		CSA WA	121
rs113102683^1,2	C,	--	108337663(+)	`GGCTT-/CCCCCC`	13	--	ut5¹		1		CSA	2
rs113219338^1,2	C	--	108338039(+)	`GGTGGA/GGGGGA`	26	G	syn¹		0	--	--	--	--
rs72101402^1,2	C,	--	108338370(+)	`TTCTA-/CCCCCC`	13	--	int¹		0	--	--	--	--
rs78171030^1,2	F,	--	108339297(+)	`CTCTCT/CCCCTC`	13	--	int¹		1		EA	120

HapMap Linkage Disequilibrium report for TCF7L2 (114710009 - 114927437 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for TCF7L2
1 CNV: 1232
Human Gene Mutation Database (HGMD): TCF7L2

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TCF7L2

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

TCF7L2 for disorders           About GeneDecksing

OMIM gene information: 602228
OMIM disorders: 125853
UniProtKB/Swiss-Prot: TF7L2_HUMAN, Q9NQB0

Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of

stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and

constitute the primary transforming event in colorectal cancer (CRC)

Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus

(NIDDM) [MIM:125853]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and

insulin resistance

20/71 diseases for TCF7L2 (see all 71): About MalaCards

pitt-hopkins syndrome familial adenomatous polyposis maturity-onset diabetes of the young adenomatous polyposis coli

tropical calcific pancreatitis nonalcoholic steatohepatitis clear cell renal cell carcinoma type 2 diabetes mellitus

diabetes mellitus glucose intolerance neonatal diabetes mellitus acute insulin response

polycystic ovary syndrome insulin resistance polyposis arterial calcification

diabetes, type 2 esophageal squamous cell carcinoma renal cell carcinoma squamous cell carcinoma

1 disease from the University of Copenhagen DISEASES database for TCF7L2:

Diabetes mellitus

10/30 Novoseek disease relationships for TCF7L2 gene (see all 30) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
familial adenomatous polyposis	70.6	5	14610217 (1), 10080941 (1), 15591320 (1), 15972967 (1)
colon cancer	61.9	21	11876551 (2), 18268068 (2), 18398040 (2), 18182714 (1) (see all 13)
colorectal tumors	59.2	8	18992165 (2), 11528255 (2), 11980438 (1), 17408638 (1) (see all 5)
microsatellite instability	57.3	9	17659738 (2), 10485457 (1), 11876551 (1), 15905022 (1) (see all 8)
colorectal cancer	53.2	18	16547505 (3), 19924301 (3), 10919662 (2), 10485457 (1) (see all 10)
niddm	50.2	19	19386626 (2), 18599616 (2), 17697858 (1), 18291022 (1) (see all 11)
insulin sensitivity	49.2	5	18398040 (1)
insulin resistance	45.1	2	16936218 (1), 20107109 (1)
colorectal carcinoma	44.9	1	15802015 (1)
colon carcinoma	43.3	1	10549354 (1)

Genetic Association Database (GAD): TCF7L2
Human Genome Epidemiology (HuGE) Navigator: TCF7L2 (244 documents)

Export disorders for TCF7L2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for TCF7L2 gene, integrated from 9 sources (see all 549):
(articles sorted by number of sources associating them with TCF7L2)

Utopia: connect your pdf to the dynamic
world of online information

Association of hTcf-4 gene expression and mutation with clinicopathological characteristics of hepatocellular carcinoma. (PubMed id 12378619)^{1, 4, 9} Jiang Y....Huang X.W. (2002)
Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium. (PubMed id 9916915)^{1, 2, 9} Barker N.... Clevers H. (1999)
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. (PubMed id 16415884)^{1, 2, 9} Grant S.F.A.... Stefansson K. (2006)
Identification of Tcf4 residues involved in high-affinity beta- catenin binding. (PubMed id 10080941)^{1, 2, 9} Omer C.A.... Kral A.M. (1999)
The human T cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines. (PubMed id 10919662)^{1, 2, 9} Duval A.... Hamelin R. (2000)
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. (PubMed id 9065401)^{1, 2, 9} Korinek V.... Clevers H. (1997)
Identification of c-MYC as a target of the APC pathway. (PubMed id 9727977)^{1, 2, 9} He T.-C.... Kinzler K.W. (1998)
Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4). (PubMed id 21454679)^{1, 2} Togi S.... Matsuda T. (2011)
MAD2B, a novel TCF4-binding protein, modulates TCF4-m ediated epithelial-mesenchymal transdifferentiation. (PubMed id 19443654)^{1, 2} Hong C.F....Wu C.W. (2009)
Coiled-coil domain containing 85B suppresses the beta-catenin activity in a p53-dependent manner. (PubMed id 17873903)^{1, 2} Iwai A.... Shimotohno K. (2008)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 6934	HGNC: 11641	AceView: TCF7L2	Ensembl:ENSG00000148737	euGenes: HUgn6934
ECgene: TCF7L2	Kegg: 6934	H-InvDB: TCF7L2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for TCF7L2	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TCF7L2	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for TCF7L2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TCF7L2 gene:
Search GeneIP for patents involving TCF7L2

GeneCards and IP:
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TCF7L2 Gene

transcription factor 7-like 2 (T-cell specific, HMG-box)

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TCF7L2 (Gene Symbol)
Transcription Factor 7-Like 2 (T-Cell Specific, HMG-Box)
TCF4
TCF-4
HTCF-4
HMG Box Transcription Factor 4
T-Cell Factor 4
T-Cell-Specific Transcription Factor 4
T-Cell Factor-4 Variant A
T-Cell Factor-4 Variant B
T-Cell Factor-4 Variant C
T-Cell Factor-4 Variant D
T-Cell Factor-4 Variant E
T-Cell Factor-4 Variant F
T-Cell Factor-4 Variant G
T-Cell Factor-4 Variant H
T-Cell Factor-4 Variant I
T-Cell Factor-4 Variant J
T-Cell Factor-4 Variant K
T-Cell Factor-4 Variant L
T-Cell Factor-4 Variant M
T-Cell Factor-4 Variant X2
Transcription Factor 7-Like 2

Gastric Cancer
Dyslipidemia
BREAST CARCINOMA
familial adenomatous polyposis
Colon Cancer
Microsatellite Instability
Insulin Resistance
polyposis
impaired glucose tolerance
Colorectal Cancer
Adenoma
Rectal Cancer
Astrocytoma
Carcinoma
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COLON CARCINOMA
Diabetes Gestational
immunodeficiency
insulin sensitivity
Atherosclerosis
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TCF7L2 Gene

transcription factor 7-like 2 (T-cell specific, HMG-box)

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Expression
for TCF7L2 gene

Orthologs
for TCF7L2 gene

Paralogs
for TCF7L2 gene

Genomic Variants
for TCF7L2 gene

Disorders / Diseases
for TCF7L2 gene

Publications
for TCF7L2 gene

Intellectual Property
for TCF7L2 gene

Products
for TCF7L2 gene