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TCF4 Gene

protein-coding GIFtS: 67
GCID: GC18M052889

Transcription Factor 4

See TCF4-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		SL3-3 Enhancer Factor 2² ³
ITF2² ³ ⁵		PTHS² ⁵
SEF2² ³ ⁵		E2-2²
Class B Basic Helix-Loop-Helix Protein 19² ³		SEF2-1²
Immunoglobulin Transcription Factor 2² ³		SEF2-1A²
ITF-2² ³		SEF2-1B²
SEF-2² ³		SEF2-1D²
TCF-4² ³		BHLHB19³
bHLHb19² ³

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, GeneCards, 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 type 2 diabetes mellitus. GO annotations related to this gene include protein C-terminus binding 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence at NCBI GenBank:

NC_000018.9 NT_010966.15 NC_018929.2

Regulatory elements:

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 Chromatin IP Primers for TCF4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing 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 ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., eBioscience, antibodies-online, and/or GeneTex,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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). Interacts with AGBL1

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 B7Z6Y1 G0LNT9 G0LNU0 G0LNU1 G0LNU2

G0LNU5 G0LNU8 G0LNU9 G0LNV0 G0LNV1 H3BPQ1 Q08AP2 Q08AP3 Q15439 Q15440 Q15441

Alternative splicing: 14 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 P15884-14

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

Explore proteomics data for TCF4 at MOPED

Post-translational modifications:

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

See TCF4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (12 alternative transcripts):

NP_001077431.1 NP_001230155.2 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

TCF4 Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	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.
	Search eBioscience for Proteins for TCF4
	Search GeneTex for Proteins for TCF4
	antibodies-online proteins for TCF4 (3 products)
	antibodies-online peptides for TCF4

TCF4 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TCF4
	Browse R&D Systems for Antibodies
	OriGene Antibodies for TCF4 OriGene Custom Antibody Services for TCF4
	Novus Biologicals TCF4 Antibodies
	Abcam antibodies for TCF4
	Browse Antibodies at Cloud-Clone Corp.
	ThermoFisher Antibodies for TCF4
	antibodies-online antibodies for TCF4 (41 products)

TCF4 Assay Products:

	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.
	Search eBioscience for ELISAs for TCF4
	antibodies-online kits for TCF4 (9 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GenesLikeMe)
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

Find genes that share domains with TCF4 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
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): Selected molecular function terms (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

Find genes that share ontologies with TCF4 About GenesLikeMe

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/body	hearing/vestibular/ear	hematopoietic system
immune system	limbs/digits/tail	mortality/aging	nervous system	skeleton

Find genes that share phenotypes with TCF4 About GenesLikeMe

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

genOway: Develop your customized and physiologically relevant rodent model for TCF4

Transcription Factor Targeting:

		Selected GeneGlobe predicted Target genes for TCF4 (see all 562):
		AASDH, ABCA7, ACR, ACTBL2, AFAP1L1, AGAP4, AGAP7, AGAP8, AGBL3, AGBL4

miRNA Products:		miRTarBase miRNAs that target TCF4: hsa-let-7e-5p (MIRT051694), hsa-mir-19b-3p (MIRT031229), hsa-mir-204-5p (MIRT005846), hsa-mir-130b-3p (MIRT020336)

		Block miRNA regulation of human, mouse, rat TCF4 using miScript Target Protectors
		Selected qRT-PCR 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:		OriGene RNAi products in human, mouse, rat for TCF4
		Predesigned siRNA for gene silencing in human, mouse, rat TCF4

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TCF4

Clone Products:		OriGene clones in human, mouse for TCF4 (see all 11) 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
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TCF4
		Addgene plasmids for TCF4

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TCF4
		Browse ESI BIO Cell Lines and PureStem Progenitors for TCF4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TCF4

Flow Cytometry
Products:

eBioscience FlowRNA Probe Sets ( VA6-11201) for TCF4

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Subcellular locations from UniProtKB/Swiss-Prot

ITF2_HUMAN, P15884: Nucleus

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
nucleus	5
cytosol	2
cytoskeleton	1

About this image

Gene Ontology (GO): 2 cellular component terms: About this table

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

Find genes that share ontologies with TCF4 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to 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 GenesLikeMe, Interaction Networks according to QIAGEN, 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 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

SuperPaths for TCF4 About (see all 15)

See pathways by source

Powered
by

SuperPath

Contained pathways About

ERK Signaling

	MAPK Signaling	0.58			ILK Signaling	0.49
	Molecular Mechanisms of Cancer	0.51

CDO in myogenesis

Myogenesis

1.00

CDO in myogenesis

1.00

Human Embryonic Stem Cell Pluripotency

Human Embryonic Stem Cell Pluripotency

0.50

Factors Promoting Cardiogenesis in Vertebrates

0.50

L1CAM interactions

Developmental Biology

0.63

Non-Canonical Wnt Pathway

Canonical Wnt Pathway

0.53

Find genes that share SuperPaths with TCF4 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TCF4 (see all 10)

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

5 BioSystems Pathways for TCF4

	Neural Crest Differentiation
	Wnt Signaling Pathway NetPath
	Corticotropin-releasing hormone
	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

1 Reactome Pathway for TCF4

CDO in myogenesis

Pathway & Disease-focused RT² Profiler 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

Interactions:

GeneGlobe Interaction Network for TCF4

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

Selected Interacting proteins for TCF4 (P15884^{1, 2, 3} ENSP00000346440⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 125)

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
FERMT2	Q96AC1¹^,²	EBI-533224,EBI-4399465 MINT-8398937 MINT-8399030 MINT-8398862 MINT-8398882 MINT-8398896 MINT-8398917 MINT-8398954
ASCL1	P50553¹^,³, ENSP00000266744⁴	EBI-533224,EBI-957042 I2D: score=4 STRING: ENSP00000266744
DAXX	Q9UER7³, ENSP00000266000⁴	I2D: score=2 STRING: ENSP00000266000
ENSG00000206206	Q9UER7³	I2D: score=2

About this table

Gene Ontology (GO): Selected biological process terms (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-templated transcription, initiation	ISS	8978694
GO:0006355	regulation of transcription, DNA-templated	--	--
GO:0006367	transcription initiation from RNA polymerase II promoter	ISS	8978694
GO:0045666	positive regulation of neuron differentiation	ISS	--

Find genes that share ontologies with TCF4 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, Sets of similar genes according to GenesLikeMe)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

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)

Find genes that share compounds with TCF4 About GenesLikeMe

(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,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
About This Section

REFSEQ mRNAs for TCF4 gene (37 alternative transcripts):

NM_001083962.1 NM_001243226.2 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 XM_005266739.2 XM_005266741.2 XM_005266743.2 XM_005266744.2

XM_005266745.2 XM_005266746.2 XM_005266747.2 XM_005266749.2 XM_005266750.2 XM_005266752.2 XM_005266754.2 XM_005266755.2

XM_005266761.2 XM_006722529.1 XM_006722530.1 XM_006722531.1 XM_006722532.1 XM_006722533.1 XM_006722534.1 XM_006722535.1

XM_006722536.1 XM_006722537.1 XM_006722538.1 XM_006722539.1 XM_006722540.1

Unigene Cluster for TCF4:

Transcription factor 4

Hs.605153 [show with all ESTs]

Unigene Representative Sequence: NM_001083962

Selected 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:		Block miRNA regulation of human, mouse, rat TCF4 using miScript Target Protectors
		Selected qRT-PCR 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:		OriGene RNAi products in human, mouse, rat for TCF4
		Predesigned siRNA for gene silencing in human, mouse, rat TCF4

Clone Products:		OriGene clones in human, mouse for TCF4 (see all 11) 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)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TCF4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TCF4
		Addgene plasmids for TCF4

Primer Products:		OriGene qSTAR qPCR primer pairs in human, mouse for TCF4
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat TCF4
		QuantiTect SYBR Green Assays in human, mouse, rat TCF4
		QuantiFast Probe-based Assays in human, mouse, rat TCF4

Flow Cytometry
Products:

eBioscience FlowRNA Probe Sets ( VA6-11201) for 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

Selected 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

Selected 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

Selected 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 GenesLikeMe, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TCF4 expression in normal human tissues (normalized intensities)
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
selected tissues (see all 13) fully expand


Brain (Nervous System) fully expand to see all 6 entries
Cerebral Cortex

Blood (Hematopoietic System) fully expand to see all 5 entries
Mature B-Cells Peripheral Blood
Peripheral blood-derived hematopoietic stem cells (family)

Tendon & Ligament
Cranial Tendons Cells Branchial Arch 1

Mesoderm (Gastrulation Derivatives)
Limb Bud Mesenchyme Cells Limb Bud

Eye (Sensory Organs) fully expand to see all 4 entries
nGnG Amacrine Cells Inner Nuclear Layer

TCF4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

TCF4 Protein Expression

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

Pathway & Disease-focused RT² Profiler 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 Selected 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}	92.64(n)¹ 98.2(a)¹		18 (43.23 cM)⁵ 21413¹ NM_013685.2¹ NP_038713.1¹ 69344146⁵
chicken (Gallus gallus)	Aves	TCF4⁶	transcription factor 4	81(a)	1 ↔ 1	Z(21-138234)
lizard (Anolis carolinensis)	Reptilia	TCF4⁶	transcription factor 4	95(a)	1 ↔ 1	GL343213.1(524011-985687)
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)	1 ↔ many 1 ↔ many	21(1794705-1800202) ENSDARG00000075546 21(1602919-1689003) ENSDARG00000087652
fruit fly (Drosophila melanogaster)	Insecta	da³	oogenesis transcription factor	78(a)		--
worm (Caenorhabditis elegans)	Secernentea	hlh-2⁶	Protein HLH-2, isoform a (hlh-2) mRNA, complete cd...	24(a)	1 → many	I(7190848-7193916) WBGene00001949

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,Sets of similar genes according to GenesLikeMe)
About This Section

Paralogs for TCF4 gene

TCF12² TCF3²

Selected SIMAP similar genes for TCF4 using alignment to 31 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

Find genes that share paralogs with TCF4 About GenesLikeMe

(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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
About This Section

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) Selected 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

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing TCF4

DNA2.0 Custom Variant and Variant Library Synthesis for TCF4

(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, Sets of similar genes according to GenesLikeMe)
About This Section

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

6 diseases for TCF4:
About MalaCards

pitt-hopkins syndrome type 2 diabetes mellitus primary sclerosing cholangitis fuchs' endothelial dystrophy

corneal dystrophy, fuchs endothelial, 4 mental retardation, autosomal dominant 6

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

Fuchs' endothelial dystrophy

Find genes that share disorders with TCF4 About GenesLikeMe

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)
About This Section

PubMed articles for TCF4 gene, integrated from 10 sources (see all 249):
(articles sorted by number of sources associating them with TCF4)

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. (Hum. Mol. Genet. 1997)
Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor. (PubMed id 2308860)^{1, 2, 3} Henthorn P.... Kadesch T. (Nucleic Acids Res. 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. (J. Virol. 1991)
Common variants conferring risk of schizophrenia. (PubMed id 19571808)^{1, 4, 9} Stefansson H....Collier D.A. (Nature 2009)
Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy and alter protein-protein interaction with TCF4. (PubMed id 24094747)^{1, 2} Riazuddin S.A....Gottsch J.D. (Am. J. Hum. Genet. 2013)
Functional analysis of TCF4 missense mutations that cause Pitt- Hopkins syndrome. (PubMed id 22777675)^{1, 2} Forrest M....Blake D.J. (Hum. Mutat. 2012)
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. (Hum. Mutat. 2012)
Genome-wide association study identifies five new schizophrenia loci. (PubMed id 21926974)^{1, 4} (Nat. Genet. 2011)
Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and splicing. (PubMed id 21789225)^{1, 2} Sepp M.... Timmusk T. (PLoS ONE 2011)
Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)^{1, 4} Rose J.E....Uhl G.R. (Mol. Med. 2010)

(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: 6925	HGNC: 11634	AceView: TCF4	Ensembl:ENSG00000196628	euGenes: HUgn6925
ECgene: TCF4	H-InvDB: TCF4

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and 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.)

About This Section

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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Transcription Factor 4

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