Human Gene TCF4 (uc010xdw.1) Description and Page Index
  Description: Homo sapiens transcription factor 4 (TCF4), transcript variant 9, mRNA.
RefSeq Summary (NM_001243233): 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. In addition, an intronic CTG repeat normally numbering 10-37 repeat units can expand to >50 repeat units and cause Fuchs endothelial corneal dystrophy. Multiple alternatively spliced transcript variants that encode different proteins have been described. [provided by RefSeq, Jul 2016].
Transcript (Including UTRs)
   Position: hg19 chr18:52,889,562-53,089,723 Size: 200,162 Total Exon Count: 16 Strand: -
Coding Region
   Position: hg19 chr18:52,895,456-53,018,213 Size: 122,758 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr18:52,889,562-53,089,723)mRNA (may differ from genome)Protein (537 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
H-INVHGNCLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCETreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: ITF2_HUMAN
DESCRIPTION: RecName: Full=Transcription factor 4; Short=TCF-4; AltName: Full=Class B basic helix-loop-helix protein 19; Short=bHLHb19; AltName: Full=Immunoglobulin transcription factor 2; Short=ITF-2; AltName: Full=SL3-3 enhancer factor 2; Short=SEF-2;
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'.
SUBUNIT: Efficient DNA binding requires dimerization with another bHLH protein. Forms homo- or heterooligomers with myogenin. Interacts with HIVEP2. Interacts with NEUROD2 (By similarity).
INTERACTION: P50553:ASCL1; NbExp=7; IntAct=EBI-533224, EBI-957042;
SUBCELLULAR LOCATION: Nucleus (Probable).
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.
DOMAIN: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
DISEASE: Defects in TCF4 are a cause of Pitt-Hopkins syndrome (PTHS) [MIM:610954]. PTHS is a rare syndromic encephalopathy characterized by severe psychomotor delay, epilepsy, daily bouts of diurnal hyperventilation starting in infancy, mild postnatal growth retardation, postnatal microcephaly, and distinctive facial features. Since most hitherto reported cases have been sporadic, with males and females equally affected, PTHS is regarded as an autosomal dominant condition.
SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain.
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;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TCF4
CDC HuGE Published Literature: TCF4
Positive Disease Associations: Fuchs Endothelial Dystrophy , schizophrenia , Survival
Related Studies:
  1. Fuchs Endothelial Dystrophy
    Keith H Baratz et al. The New England journal of medicine 2010, E2-2 protein and Fuchs's corneal dystrophy., The New England journal of medicine. [PubMed 20825314]
    Genetic variation in TCF4 contributes to the development of FCD. (Funded by the National Eye Institute and others.)
  2. schizophrenia
    International Schizophrenia Consortium ,et al. 2009, Common polygenic variation contributes to risk of schizophrenia and bipolar disorder, Nature 2009 460- 7256 : 748-52. [PubMed 19571811]
  3. schizophrenia
    Stefansson ,et al. 2009, Common variants conferring risk of schizophrenia, Nature 2009 460- 7256 : 744-7. [PubMed 19571808]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: TCF4
Diseases sorted by gene-association score: pitt-hopkins syndrome* (1712), corneal dystrophy, fuchs endothelial, 3* (1019), fuchs' endothelial dystrophy* (265), intellectual disability* (241), alacrima, achalasia, and mental retardation syndrome* (121), autosomal dominant non-syndromic intellectual disability* (88), cholangitis, primary sclerosing* (13), corneal dystrophy (13), non-syndromic intellectual disability (8), diabetes mellitus, insulin-dependent, 6 (6), blastic plasmacytoid dendritic cell (6), constipation (6), colorectal cancer (3), angelman syndrome (2), eye disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.72 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 355.67 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -95.40399-0.239 Picture PostScript Text
3' UTR -1410.145704-0.247 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011598 - HLH_dom

Pfam Domains:
PF00010 - Helix-loop-helix DNA-binding domain

SCOP Domains:
47459 - HLH, helix-loop-helix DNA-binding domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2KWF
- NMR MuPIT


ModBase Predicted Comparative 3D Structure on P15884
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001011 transcription factor activity, sequence-specific DNA binding, RNA polymerase recruiting
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001093 TFIIB-class transcription factor binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043425 bHLH transcription factor binding
GO:0046982 protein heterodimerization activity
GO:0046983 protein dimerization activity
GO:0070888 E-box binding

Biological Process:
GO:0006351 transcription, DNA-templated
GO:0006352 DNA-templated transcription, initiation
GO:0006355 regulation of transcription, DNA-templated
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007399 nervous system development
GO:0030154 cell differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0065004 protein-DNA complex assembly

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005667 transcription factor complex
GO:0070369 beta-catenin-TCF7L2 complex
GO:1990907 beta-catenin-TCF complex


-  Descriptions from all associated GenBank mRNAs
  M74718 - Human SEF2-1A protein (SEF2-1A) mRNA, 5' end.
AK300038 - Homo sapiens cDNA FLJ54545 complete cds, highly similar to Transcription factor 4.
AK096862 - Homo sapiens cDNA FLJ39543 fis, clone PUAEN2008939, highly similar to TRANSCRIPTION FACTOR 4.
AK301144 - Homo sapiens cDNA FLJ58695 complete cds, highly similar to Transcription factor 4.
M74719 - Human SEF2-1B protein (SEF2-1B) mRNA, complete cds.
AK299169 - Homo sapiens cDNA FLJ58684 complete cds, highly similar to Transcription factor 4.
AB209741 - Homo sapiens mRNA for transcription factor 4 isoform b variant protein.
AK300636 - Homo sapiens cDNA FLJ53660 complete cds, highly similar to Transcription factor 4.
AK095041 - Homo sapiens cDNA FLJ37722 fis, clone BRHIP2019186, highly similar to TRANSCRIPTION FACTOR 4.
X52079 - H.sapiens transcription factor (ITF-2) mRNA, 3' end.
AK300612 - Homo sapiens cDNA FLJ61772 complete cds, highly similar to Transcription factor 4.
AK122765 - Homo sapiens cDNA FLJ16304 fis, clone PUAEN2003408, highly similar to TRANSCRIPTION FACTOR 4.
BC125084 - Homo sapiens transcription factor 4, mRNA (cDNA clone MGC:149723 IMAGE:40117795), complete cds.
BC125085 - Homo sapiens transcription factor 4, mRNA (cDNA clone MGC:149724 IMAGE:40117798), complete cds.
FR748222 - Homo sapiens mRNA for transcription factor 4 isoform H- (TCF4 gene).
FR748220 - Homo sapiens mRNA for transcription factor 4 isoform A+ (TCF4 gene).
FR748221 - Homo sapiens mRNA for transcription factor 4 isoform A- (TCF4 gene).
FR748218 - Homo sapiens mRNA for transcription factor 4 isoform D- (TCF4 gene).
FR748219 - Homo sapiens mRNA for transcription factor 4 isoform G- (TCF4 gene).
FR748217 - Homo sapiens mRNA for transcription factor 4 isoform F- (TCF4 gene).
FR748214 - Homo sapiens mRNA for transcription factor 4 isoform C- (TCF4 gene).
FR748215 - Homo sapiens mRNA for transcription factor 4 isoform C- delta (TCF4 gene).
FR748210 - Homo sapiens mRNA for transcription factor 4 isoform B+ (TCF4 gene).
FR748211 - Homo sapiens mRNA for transcription factor 4 isoform B- (TCF4 gene).
FR748212 - Homo sapiens mRNA for transcription factor 4 isoform B+ delta (TCF4 gene).
FR748213 - Homo sapiens mRNA for transcription factor 4 isoform B- delta (TCF4 gene).
FR748216 - Homo sapiens mRNA for transcription factor 4 isoform E- (TCF4 gene).
BC031056 - Homo sapiens transcription factor 4, mRNA (cDNA clone IMAGE:5273193).
AK316165 - Homo sapiens cDNA, FLJ79064 complete cds, highly similar to Transcription factor 4.
AK315074 - Homo sapiens cDNA, FLJ96028.
KJ897642 - Synthetic construct Homo sapiens clone ccsbBroadEn_07036 TCF4 gene, encodes complete protein.
KJ905937 - Synthetic construct Homo sapiens clone ccsbBroadEn_15607 TCF4 gene, encodes complete protein.
KR711928 - Synthetic construct Homo sapiens clone CCSBHm_00032181 TCF4 (TCF4) mRNA, encodes complete protein.
KR711929 - Synthetic construct Homo sapiens clone CCSBHm_00032187 TCF4 (TCF4) mRNA, encodes complete protein.
KR711930 - Synthetic construct Homo sapiens clone CCSBHm_00032188 TCF4 (TCF4) mRNA, encodes complete protein.
KR711931 - Synthetic construct Homo sapiens clone CCSBHm_00032190 TCF4 (TCF4) mRNA, encodes complete protein.
AB527692 - Synthetic construct DNA, clone: pF1KB6272, Homo sapiens TCF4 gene for transcription factor 4, without stop codon, in Flexi system.
KJ901782 - Synthetic construct Homo sapiens clone ccsbBroadEn_11176 TCF4 gene, encodes complete protein.
CR933675 - Homo sapiens mRNA; cDNA DKFZp781D0421 (from clone DKFZp781D0421).
FR748208 - Homo sapiens partial mRNA for transcription factor 4 isoform D (TCF4 gene).
FR748209 - Homo sapiens partial mRNA for transcription factor 4 isoform D (TCF4 gene).
FR748207 - Homo sapiens partial mRNA for transcription factor 4 isoform R (TCF4 gene).
FR748205 - Homo sapiens partial mRNA for transcription factor 4 isoform B (TCF4 gene).
AK095066 - Homo sapiens cDNA FLJ37747 fis, clone BRHIP2022986.
AK021980 - Homo sapiens cDNA FLJ11918 fis, clone HEMBB1000272.
JD021349 - Sequence 2373 from Patent EP1572962.
JD224243 - Sequence 205267 from Patent EP1572962.
JD280261 - Sequence 261285 from Patent EP1572962.
AK026674 - Homo sapiens cDNA: FLJ23021 fis, clone LNG01014, highly similar to HUMSEF21B Human SEF2-1B protein (SEF2-1B) mRNA.
JD056954 - Sequence 37978 from Patent EP1572962.
JD046741 - Sequence 27765 from Patent EP1572962.
FR748223 - Homo sapiens mRNA for transcription factor 4 isoform I- (TCF4 gene).
M74720 - Human SEF2-1D protein (SEF2-1D) mRNA, partial cds.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P15884 (Reactome details) participates in the following event(s):

R-HSA-448962 Heterodimerization of E proteins with Myod
R-HSA-448963 Interaction of MyoD:E protein with MEF2
R-HSA-375170 CDO in myogenesis
R-HSA-525793 Myogenesis
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B4DT37, BHLHB19, G0LNT9, G0LNU0, G0LNU1, G0LNU2, G0LNU8, G0LNU9, G0LNV0, G0LNV1, ITF2, ITF2_HUMAN, NM_001243233, NP_001230162, P15884, Q08AP2, Q08AP3, Q15439, Q15440, Q15441, SEF2
UCSC ID: uc010xdw.1
RefSeq Accession: NM_001243233
Protein: P15884 (aka ITF2_HUMAN)
CCDS: CCDS58626.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TCF4:
hirschsprung-ov (Hirschsprung Disease Overview)
pitt-hopkins (Pitt-Hopkins Syndrome)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001243233.1
exon count: 16CDS single in 3' UTR: no RNA size: 7717
ORF size: 1614CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3196.50frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.