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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TCF4 Gene

protein-coding GIFtS: 68
GCID: GC18M052889

Transcription Factor 4

43 related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
Transcription Factor 4¹ ²		bHLHb19² ³
ITF2² ³ ⁵		SL3-3 Enhancer Factor 2² ³
SEF2² ³ ⁵		PTHS² ⁵
Class B Basic Helix-Loop-Helix Protein 19² ³		E2-2²
Immunoglobulin Transcription Factor 2² ³		SEF2-1²
ITF-2² ³		SEF2-1A²
SEF-2² ³		SEF2-1B²
TCF-4² ³		BHLHB19³

External Ids:	HGNC: 11634¹	Entrez Gene: 6925²	Ensembl: ENSG00000196628⁷	OMIM: 602272⁵	UniProtKB: P15884³

Export aliases for TCF4 gene to outside databases

Previous GC identifers: GC18M052983 GC18M052797 GC18M052679 GC18M051043 GC18M051045 GC18M049599

(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 TCF4 Gene:

This gene encodes transcription factor 4, a basic helix-loop-helix transcription factor. The encoded protein

recognizes an Ephrussi-box ('E-box') binding site ('CANNTG') - a motif first identified in immunoglobulin

enhancers. This gene is broadly expressed, and may play an important role in nervous system development. Defects

in this gene are a cause of Pitt-Hopkins syndrome. Multiple alternatively spliced transcript variants that encode

different proteins have been described. (provided by RefSeq, Aug 2011)

GeneCards Summary for TCF4 Gene:

TCF4 (transcription factor 4) is a protein-coding gene. Diseases associated with TCF4 include pitt-hopkins syndrome, and fuchs' endothelial dystrophy, and among its related super-pathways are MAPK Signaling and Myogenesis. GO annotations related to this gene include transcription corepressor activity and sequence-specific DNA binding transcription factor activity. An important paralog of this gene is TCF12.

UniProtKB/Swiss-Prot: ITF2_HUMAN, P15884

Function: Transcription factor that binds to the immunoglobulin enchancer Mu-E5/KE5-motif. Involved in the

initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to

the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By

similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'

Gene Wiki entry for TCF4 Gene

(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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000018.9 NT_025028.14 NC_018929.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TCF4 gene promoter:
FOXD3 C/EBPalpha E47 CREB SRY Nkx6-1 deltaCREB POU2F1a Zic3
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TCF4 promoter sequence

Search SABiosciences Chromatin IP Primers for TCF4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TCF4

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

Entrez Gene cytogenetic band: 18q21.1 Ensembl cytogenetic band: 18q21.2 HGNC cytogenetic band: 18q21.1

TCF4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TCF4 gene location

GeneLoc information about chromosome 18 GeneLoc Exon Structure

GeneLoc location for GC18M052889: view genomic region (about GC identifiers)

Start:	52,889,562 bp from pter	End:	53,332,018 bp from pter
Size:	442,457 bases	Orientation:	minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB 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 Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: ITF2_HUMAN, P15884 (See protein sequence)

Recommended Name: Transcription factor 4

Size: 667 amino acids; 71308 Da

Subunit: Efficient DNA binding requires dimerization with another bHLH protein. Forms homo- or heterooligomers

with myogenin. Interacts with HIVEP2. Interacts with NEUROD2 (By similarity). The CTNNB1 and TCF4 complex

interacts with PML (isoform PML-4). Identified in a complex with CTNNB1 and FERMT2

Subcellular location: Nucleus

Sequence caution: Sequence=AAA60310.1; Type=Miscellaneous discrepancy; Note=Incomplete and probable erroneous

sequence; Sequence=AAA60312.1; Type=Miscellaneous discrepancy; Note=Incomplete and probable erroneous sequence;

1 PDB 3D structure from and Proteopedia for TCF4:

2KWF (3D)

Secondary accessions: B3KT62 B3KUC0 B4DT37 B4DUG3 B7Z5M6 G0LNT9 G0LNU0 G0LNU1 G0LNU2 G0LNU5

G0LNU8 G0LNU9 G0LNV0 G0LNV1 H3BPQ1 Q08AP2 Q08AP3 Q15439 Q15440 Q15441

Alternative splicing: 13 isoforms: P15884-1 P15884-2 P15884-3 P15884-4 P15884-5 P15884-6 P15884-7 P15884-8

P15884-9 P15884-10 P15884-11 P15884-12 P15884-13

Explore the universe of human proteins at neXtProt for TCF4: NX_P15884

Explore proteomics data for TCF4 at MOPED

Post-translational modifications:

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_P15884

TCF4 Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins (12 alternative transcripts):

NP_001077431.1 NP_001230155.1 NP_001230156.1 NP_001230157.1 NP_001230159.1 NP_001230160.1 NP_001230161.1 NP_001230162.1

NP_001230163.1 NP_001230164.1 NP_001230165.1 NP_003190.1

ENSEMBL proteins:

ENSP00000348374 ENSP00000455135 ENSP00000409447 ENSP00000439656 ENSP00000445202

ENSP00000440731 ENSP00000457649 ENSP00000455346 ENSP00000439827 ENSP00000441562

ENSP00000455179 ENSP00000457765 ENSP00000455984 ENSP00000455763 ENSP00000455261

ENSP00000454366 ENSP00000455418 ENSP00000456125 ENSP00000457263 ENSP00000381382

ENSP00000454647 ENSP00000468729 ENSP00000455304 ENSP00000456983 ENSP00000457392

ENSP00000455071 ENSP00000458122 ENSP00000456802 ENSP00000457245 ENSP00000454584

ENSP00000468277 ENSP00000456220 ENSP00000457113 ENSP00000455163 ENSP00000456917

ENSP00000457747 ENSP00000454328 ENSP00000455450 ENSP00000454866 ENSP00000454352

ENSP00000457082 ENSP00000454441 ENSP00000346440

Reactome Protein details: P15884
Human Recombinant Protein Products for TCF4:

	Browse Purified and Recombinant Proteins at EMD Millipore
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	OriGene Purified Proteins for TCF4 OriGene Protein Over-expression Lysate for TCF4 OriGene MassSpec for TCF4 OriGene Custom Protein Services for TCF4
	GenScript Custom Purified and Recombinant Proteins Services for TCF4
	Novus Biologicals TCF4 Protein Novus Biologicals TCF4 Lysates
	Browse Sino Biological Recombinant Proteins Browse Sino Biological Cell Lysates
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Cloud-Clone Corp.

Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	1681116
GO:0005667	transcription factor complex	ISS	8978694

TCF4 for ontologies About GeneDecksing

TCF4 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
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	GenScript Custom Superior Antibodies Services for TCF4
	Novus Biologicals TCF4 Antibodies
	Abcam antibodies for TCF4
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	ThermoFisher Antibodies for TCF4
	LSBio Antibodies in human, mouse, rat for TCF4

Assay Products for TCF4:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for TCF4
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for TCF4
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.

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

HGNC Gene Families:

bHLH: Basic helix-loop-helix proteins

1 InterPro protein domain:

IPR011598 bHLH_dom

Graphical View of Domain Structure for InterPro Entry P15884

ProtoNet protein and cluster: P15884

1 Blocks protein domain: IPB001092 Basic helix-loop-helix dimerization domain bHLH

UniProtKB/Swiss-Prot: ITF2_HUMAN, P15884

Domain: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription

factors

Similarity: Contains 1 bHLH (basic helix-loop-helix) domain

TCF4 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
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, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: ITF2_HUMAN, P15884

Function: Transcription factor that binds to the immunoglobulin enchancer Mu-E5/KE5-motif. Involved in the

initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to

the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By

similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'

Genatlas biochemistry entry for TCF4:

transcription factor 4,with several alternatively spliced isoforms

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	ISS	8978694
GO:0001011	sequence-specific DNA binding RNA polymerase recruiting transcription factor activity	ISS	8978694
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription	ISS	8978694
GO:0001087	TFIIB-class binding transcription factor activity	ISS	8978694
GO:0001093	TFIIB-class transcription factor binding	ISS	8978694

TCF4 for ontologies About GeneDecksing

Phenotypes:
3 GenomeRNAi human phenotypes for TCF4:

Increased cell death HMECs cel

Increased viability with TRAIL

Wnt reporter downregulated

10 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Tcf4):

cellular	craniofacial	growth/size	hearing/vestibular/ear	hematopoietic system
immune system	limbs/digits/tail	mortality/aging	nervous system	skeleton

TCF4 for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-outs for TCF4: Tcf4^tm1Zhu Tcf4^tm1.1Hmb

inGenious Targeting Laboratory - Custom generated mouse model solutions for TCF4

inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for TCF4

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TCF4

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TCF4

		10/571 SABiosciences Target genes for TCF4 (see all 571):
		AASDH ABCA7 ACR ACTBL2 AFAP1L1 AGAP4 AGAP7 AGAP8 AGBL3 AGBL4

miRNA Products:		miRTarBase miRNAs that target TCF4: hsa-mir-204 (MIRT005846)

		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TCF4
		8/187 QIAGEN miScript miRNA Assays for microRNAs that regulate TCF4 (see all 187):
		hsa-miR-193a-3p hsa-miR-106a hsa-miR-4305 hsa-miR-605 hsa-miR-128 hsa-miR-138-2* hsa-miR-519a hsa-miR-200b

		Browse SwitchGear 3'UTR luciferase reporter plasmids

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene RNAi products in human, mouse, rat for TCF4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TCF4

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for TCF4
			Sirion Biotech Customized adenovirus for overexpression of TCF4

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene clones in human, mouse for TCF4 (see all 13) OriGene ORF clones in mouse, rat for TCF4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): TCF4 (NM_001083962)
		Sino Biological Human cDNA Clone for TCF4
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TCF4
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		Sirion Biotech Customized lentivirus for stable overexpression of TCF4 Customized lentivirus expression plasmids for stable overexpression of TCF4

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TCF4
		Search LifeMap BioReagents cell lines for TCF4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TCF4

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, 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 Oct 2013 via Entrez Gene).
About This Section

SuperPaths for TCF4 About (see all 15)

See pathways by source

SuperPath

Contained pathways About

Rho Family GTPases

	MAPK Signaling	0.58			ILK Signaling	0.49
	Molecular Mechanisms of Cancer	0.51

CDO in myogenesis

CDO in myogenesis

1.00

Myogenesis

1.00

Human Embryonic Stem Cell Pluripotency

Human Embryonic Stem Cell Pluripotency

0.50

Factors Promoting Cardiogenesis in Vertebrates

0.50

Axon guidance

Developmental Biology

0.69

Canonical Wnt Pathway

Canonical Wnt Pathway

0.53

Pathways by source See SuperPaths
Show all pathways

1 EMD Millipore Pathway for TCF4

Selected targets of Oct-3/4

5/10 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for TCF4 (see all 10)

	MAPK Signaling
	Factors Promoting Cardiogenesis in Vertebrates
	Molecular Mechanisms of Cancer
	Colorectal Cancer Metastasis
	Glioblastoma Multiforme

4 BioSystems Pathways for TCF4

	Neural Crest Differentiation
	Wnt Signaling Pathway NetPath
	Coregulation of Androgen receptor activity
	Regulation of Wnt-mediated beta catenin signaling and target gene transcription

1 Sino Biological Pathway for TCF4

Canonical Wnt Pathway

3 Reactome Pathways for TCF4

	Developmental Biology
	Myogenesis
	CDO in myogenesis

TCF4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TCF4

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

5/57 Interacting proteins for TCF4 (P15884^{1, 2, 3} ENSP00000346440⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 57)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CTNNB1	P35222¹^,²^,³, ENSP00000344456⁴	EBI-533224,EBI-491549 MINT-8399030 MINT-8398882 MINT-8398896 MINT-8398917 MINT-4508268 MINT-8398937 MINT-8398969 MINT-8398862 MINT-4508065 I2D: score=7 STRING: ENSP00000344456
ASCL1	P50553¹^,³, ENSP00000266744⁴	EBI-533224,EBI-957042 I2D: score=4 STRING: ENSP00000266744
FERMT2	Q96AC1²	MINT-8398937 MINT-8399030 MINT-8398862 MINT-8398882 MINT-8398896 MINT-8398917 MINT-8398954
DAXX	Q9UER7³, ENSP00000266000⁴	I2D: score=2 STRING: ENSP00000266000
ENSG00000206206	Q9UER7³	I2D: score=2

About this table

Gene Ontology (GO): 5/8 biological process terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	--	--
GO:0006352	DNA-dependent transcription, initiation	ISS	8978694
GO:0006355	regulation of transcription, DNA-dependent	--	--
GO:0006367	transcription initiation from RNA polymerase II promoter	ISS	8978694
GO:0045666	positive regulation of neuron differentiation	ISS	--

TCF4 for ontologies About GeneDecksing

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

TCF4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for TCF4 (ITF2)

2 Novoseek inferred chemical compound relationships for TCF4 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
mononucleotide	48.4	3	10918391 (2)
glycogen	32	2	12603528 (1), 14687479 (1)

Search CenterWatch for drugs/clinical trials and news about TCF4 / ITF2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TCF4 gene (12 alternative transcripts):

NM_001083962.1 NM_001243226.1 NM_001243227.1 NM_001243228.1 NM_001243230.1 NM_001243231.1 NM_001243232.1 NM_001243233.1

NM_001243234.1 NM_001243235.1 NM_001243236.1 NM_003199.2

Unigene Cluster for TCF4:

Transcription factor 4

Hs.605153 [show with all ESTs]

Unigene Representative Sequence: NM_001083962

18/48 Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 48):

ENST00000356073 ENST00000568673 ENST00000457482 ENST00000543082 ENST00000540999

ENST00000537578 ENST00000564999 ENST00000568740 ENST00000562680 ENST00000537856

ENST00000544241 ENST00000561992 ENST00000561831 ENST00000565018 ENST00000570287

ENST00000564228 ENST00000567880 ENST00000566286

miRNA Products:		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TCF4
		8/187 QIAGEN miScript miRNA Assays for microRNAs that regulate TCF4 (see all 187):
		hsa-miR-193a-3p hsa-miR-106a hsa-miR-4305 hsa-miR-605 hsa-miR-128 hsa-miR-138-2* hsa-miR-519a hsa-miR-200b

		Browse SwitchGear 3'UTR luciferase reporter plasmids

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		Sirion Biotech Customized lentivirus for stable overexpression of TCF4 Customized lentivirus expression plasmids for stable overexpression of TCF4

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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TCF4
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TCF4

Additional mRNA sequence:

AB209741.1 AK021980.1 AK026674.1 AK095041.1 AK095066.1 AK096862.1 AK122765.1 AK299169.1

AK300038.1 AK300612.1 AK300636.1 AK301144.1 AK315074.1 AK316165.1 BC031056.1 BC125084.1

BC125085.1 FR748202.1 FR748203.1 FR748205.1 FR748207.1 FR748208.1 FR748209.1 FR748210.1

FR748211.1 FR748212.1 FR748213.1 FR748214.1 FR748215.1 FR748216.1 FR748217.1 FR748218.1

FR748219.1 FR748220.1 FR748221.1 FR748222.1 FR748223.1 M74718.1 M74719.1 M74720.1

X52079.1

24/47 DOTS entries (see all 47):

DT.448128 DT.86840324 DT.100892351 DT.100806486 DT.121101533 DT.100892349 DT.95169893 DT.100808993

DT.441773 DT.95292982 DT.121101581 DT.95169897 DT.121101588 DT.87079130 DT.100789378 DT.75148455

DT.75182387 DT.100892345 DT.100789379 DT.100753719 DT.75169556 DT.100892346 DT.40115779 DT.92447456

24/512 AceView cDNA sequences (see all 512):

CR604143 AI359999 BI753610 AA287097 BM787123 BU948052 AI589166 AW612439

CA312686 AI003998 AU120273 BP348534 BM669373 AA837089 BQ882546 AI638194

BQ706300 AI362674 CA776803 AA287187 AI090983 AU118026 AA677237 AA290666

GeneLoc Exon Structure

5/13 Alternative Splicing Database (ASD) splice patterns (SP) for TCF4 (see all 13) About this scheme

ExUns:	1a	·	1b	^	2	^	3	^	4	^	5	^	6	^	7	^	8	^	9	^	10	^	11	^	12	^	13	^	14	^	15	^	16	^	17a	·	17b	·	17c	^	18	^	19	^	20	^	21a	·	21b	^	22a	·
SP1:											-						-				-		-		-						-																-
SP2:											-						-				-		-		-						-																-
SP3:																	-				-		-		-						-																-
SP4:																					-		-		-						-																-
SP5:																																															-

ExUns:	22b	^	23	^	24a	·	24b	·	24c	^	25a	·	25b	^	26	^	27a	·	27b
SP1:									-		-
SP2:											-
SP3:									-		-
SP4:											-
SP5:

ECgene alternative splicing isoforms for TCF4

(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

TCF4 expression in normal human tissues (normalized intensities) TCF4 embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GGACAGATGT

About this image

TCF4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database

5/19 selected tissues (see all 19) fully expand


Brain (Nervous System) fully expand to see all 9 entries
Thalamus
brain/midbrain

Eye (Sensory Organs) fully expand to see all 4 entries
nGnG Amacrine Cells Inner Nuclear Layer
sensory organ/eye/cornea

Blood (Hematopoietic System) fully expand to see all 3 entries
Plasmacytoid Dendritic cells Peripheral Blood
Peripheral blood-derived hematopoietic stem cells

Limb (Muscoskeletal System) fully expand to see all 3 entries
Limb Bud Mesenchyme Cells Limb Bud
limb/hindlimb

Lower Urinary Tract (Urinary System) fully expand to see all 3 entries
visceral organ/urogenital sinus/nerves of urogenital sinus

See TCF4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TCF4

SOURCE GeneReport for Unigene cluster: Hs.605153

UniProtKB/Swiss-Prot: ITF2_HUMAN, P15884

Tissue specificity: Expressed in adult heart, brain, placenta, skeletal muscle and to a lesser extent in the lung.

In developing embryonic tissues, expression mostly occurs in the brain

SABiosciences Expression via Pathway-Focused PCR Arrays including TCF4:

WNT Signaling Targets in human mouse rat

WNT Signaling Pathway in human mouse rat

Liver Cancer in human mouse rat

Epithelial to Mesenchymal Transition (EMT) in human mouse rat

Cardiotoxicity in human mouse rat

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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 TCF4 gene from 7/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Tcf4^{1 , 5}	transcription factor 4^{1, 5}	92.69(n)¹ 98.21(a)¹		18 (43.23 cM)⁵ 21413¹ NM_013685.2¹ NP_038713.1¹ 69344146⁵
chicken (Gallus gallus)	Aves	TCF4⁶	transcription factor 4	80(a)	1 ↔ 1	Z(21-138234)
lizard (Anolis carolinensis)	Reptilia	TCF4⁶ --	Uncharacterized protein	95(a) 72(a)	1 ↔ 1 possible ortholog	GL343213.1(524011-985687) AAWZ02036688(11524-14458)
African clawed frog (Xenopus laevis)	Amphibia	CF342043.1²	--	80.67(n)		CF342043.1
zebrafish (Danio rerio)	Actinopterygii	CABZ01109624.1⁶ tcf4⁶	transcription factor 4	78(a) 77(a)	possible ortholog 1 ↔ 1	21(1794705-1800202) 21(1602919-1689003)
fruit fly (Drosophila melanogaster)	Insecta	da³	oogenesis transcription factor	78(a)		--
worm (Caenorhabditis elegans)	Secernentea	hlh-2⁶	Protein HLH-2, isoform a	22(a)	1 → many	I(7190848-7193916)

ENSEMBL Gene Tree for TCF4 (if available)
TreeFam Gene Tree for TCF4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for TCF4 gene

TCF12² TCF3²

18/86 SIMAP similar genes for TCF4 using alignment to 32 protein entries: ITF2_HUMAN (see all proteins) (see all similar genes):

EML2 HOOK2 VPS33A ZNF814 CRCP ZNF546

DCTN5 DNAPTP3 TCF12 SH3PXD2A UBIAD1 ZNF212

C4orf21 LAMB4 ZNF283 ZNF527 PLEKHH2 APOPT1

TCF4 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, 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)
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SNP ID	Clinical significance	Chr 18 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data				Transcription Related Data				Allele Frequencies
			--	--	--		--	--
VAR_066841⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_066841	2	R H	mis⁴		0	--	--	--	--
VAR_066840⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_066840	2	R P	mis⁴		0	--	--	--	--
VAR_066973⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_066973	2	R P	mis⁴		0	--	--	--	--
VAR_058633⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_058633	2	R G	mis⁴		0	--	--	--	--
VAR_034704⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_034704	2	R Q	mis⁴		0	--	--	--	--
VAR_066972⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_066972	2	R H	mis⁴		0	--	--	--	--
VAR_058632⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_058632	2	D G	mis⁴		0	--	--	--	--
VAR_066974⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_066974	2	A P	mis⁴		0	--	--	--	--
VAR_066971⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_066971	2	R Q	mis⁴		0	--	--	--	--
VAR_034705⁴	Pitt-Hopkins syndrome (PTHS)⁴	--	see VAR_034705	2	R W	mis⁴		0	--	--	--	--

HapMap Linkage Disequilibrium report for TCF4 (52889562 - 53139562 bp, first 250kb of TCF4)

Structural Variations
Database of Genomic Variants (DGV) 10/12 variations for TCF4 (see all 12): About this table

Variant ID	Type	Subtype	PubMed ID
esv2635967	CNV	Deletion	19546169
esv2717133	CNV	Deletion	23290073
dgv496e201	CNV	Deletion	23290073
esv2487089	CNV	Deletion	19546169
esv2659569	CNV	Deletion	23128226
esv271560	CNV	Insertion	20981092
esv273068	CNV	Insertion	20981092
nsv131347	CNV	Insertion	16902084
esv274560	CNV	Insertion	20981092
nsv2315	CNV	Loss	18451855

Human Gene Mutation Database (HGMD): TCF4

Locus Specific Mutation Databases (LSDB): TCF4

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 602272
OMIM disorders: 610954
UniProtKB/Swiss-Prot: ITF2_HUMAN, P15884

Pitt-Hopkins syndrome (PTHS) [MIM:610954]: A syndrome characterized by mental retardation, wide mouth and

distinctive facial features, and intermittent hyperventilation followed by apnea. Features include intellectual

disability with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing

anomalies, severe motor developmental delay, motor incoordination, ocular anomalies, constipation, seizures,

typical behavior and subtle brain abnormalities. Note=The disease is caused by mutations affecting the gene

represented in this entry

20/43 diseases for TCF4 (see all 43): About MalaCards

pitt-hopkins syndrome fuchs' endothelial dystrophy autonomic dysfunction corneal dystrophy

tauopathy rett syndrome primary sclerosing cholangitis endotheliitis

familial adenomatous polyposis sclerosing cholangitis myocarditis noma

endometrial carcinoma cholangitis pituitary tumors microcephaly

angelman syndrome bipolar disorder colon cancer gastric cancer

1 disease from the University of Copenhagen DISEASES database for TCF4:

Fuchs' endothelial dystrophy

TCF4 for disorders About GeneDecksing

14 Novoseek inferred disease relationships for TCF4 gene (see top 10) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
familial adenomatous polyposis	70.8	3	12460462 (1), 11396184 (1), 15342948 (1)
colon cancer	52.9	2	15667799 (1), 17167838 (1)
endometrial carcinoma	43	4	18798221 (2), 15806138 (1), 10597289 (1)
colorectal cancer	40.8	2	18439914 (1), 19376641 (1)
colorectal tumors	28.8	1	10597289 (1)
gastric cancer	27.9	13	18635522 (5), 16311123 (2), 10597289 (1)
cancer	24.7	1	15667799 (1)
hepatocellular carcinoma	21.6	6	14687479 (2), 15040893 (2), 12566320 (1)
microsatellite instability	20.9	1	10597289 (1)
tumors	14.9	16	15667799 (3), 16311123 (2), 10918391 (2), 18635522 (2) (see all 5)
leukemia	0	3	1681116 (1), 11973610 (1)
carcinoma squamous cell	0	1	15667799 (1)
metastasis	0	2	16311123 (2)
carcinoma	0	2	15806138 (1), 15667799 (1)

Genetic Association Database (GAD): TCF4
Human Genome Epidemiology (HuGE) Navigator: TCF4 (251 documents)

Export disorders for TCF4 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)
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PubMed articles for TCF4 gene, integrated from 9 sources (see all 238):
(articles sorted by number of sources associating them with TCF4)

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

A novel, heritable, expanding CTG repeat in an intron of the SEF2-1 gene on chromosome 18q21.1. (PubMed id 9302263)^{1, 2, 3} Breschel T.S.... Ross C.A. (1997)
Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor. (PubMed id 2308860)^{1, 2, 3} Henthorn P.... Kadesch T. (1990)
Helix-loop-helix transcriptional activators bind to a sequence in glucocorticoid response elements of retrovirus enhancers. (PubMed id 1681116)^{1, 2, 9} Corneliussen B.... Grundstroem T. (1991)
Common variants conferring risk of schizophrenia. (PubMed id 19571808)^{1, 4, 9} Stefansson H....Collier D.A. (2009)
Functional analysis of TCF4 missense mutations that cause Pitt- Hopkins syndrome. (PubMed id 22777675)^{1, 2} Forrest M....Blake D.J. (2012)
b-catenin inhibits promyelocytic leukemia protein tumo r suppressor function in colorectal cancer cells. (PubMed id 22155184)^{1, 2} Satow R....Yamada T. (2012)
Kindlin 2 forms a transcriptional complex with b-caten in and TCF4 to enhance Wnt signalling. (PubMed id 22699938)^{1, 2} Yu Y....Zhang H. (2012)
Genome-wide association study identifies five new schi zophrenia loci. (PubMed id 21926974)^{1, 4} (2011)
Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and s plicing. (PubMed id 21789225)^{1, 2} Sepp M....Timmusk T. (2011)
Novel comprehensive diagnostic strategy in pitt-hopkins syndrome: Clinical score and further delineation of the TCF4 mutational spectrum. (PubMed id 22045651)^{1, 2} Whalen S.... Giurgea I. (2011)

(in PubMed, OMIM, and NCBI Bookshelf)
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		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)
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Entrez Gene: 6925	HGNC: 11634	AceView: TCF4	Ensembl:ENSG00000196628	euGenes: HUgn6925
ECgene: TCF4	H-InvDB: TCF4

(According to HUGE)
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(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 TCF4	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TCF4	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for TCF4 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 TCF4 gene:
Search GeneIP for patents involving TCF4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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