Human Gene TCF4 (uc002lga.3)
Description: Homo sapiens transcription factor 4 (TCF4), transcript variant 3, mRNA.
RefSeq Summary (NM_001243226): 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 chr18:52,889,562-53,303,188 Size: 413,627 Total Exon Count: 21 Strand: -
Coding Region
Position: hg19 chr18:52,895,456-53,303,128 Size: 407,673 Coding Exon Count: 20
Data last updated at UCSC: 2013-06-14
Sequence and Links to Tools and Databases
Comments and Description Text from UniProtKB
ID: E9PH57_HUMAN
DESCRIPTION: SubName: Full=Transcription factor 4;
SIMILARITY: Contains 1 basic helix-loop-helix (bHLH) domain.CAUTION: The sequence shown here is derived from an Ensembl automatic analysis pipeline and should be considered as preliminary data.
Primer design for this transcript
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: 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.)
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 ]
schizophrenia Stefansson ,et al. 2009, Common variants conferring risk of schizophrenia, Nature 2009 460- 7256 : 744-7.
[PubMed 19571808 ]
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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)
Common Gene Haplotype Alleles
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RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
Microarray Expression Data
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mRNA Secondary Structure of 3' and 5' UTRs
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
ModBase Predicted Comparative 3D Structure on E9PH57
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.
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:0003682 chromatin binding
GO:0003714 transcription corepressor activity
GO:0005515 protein binding
GO:0043621 protein self-association
GO:0046982 protein heterodimerization activity
GO:0046983 protein dimerization activity
GO:0070888 E-box binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006352 DNA-templated transcription, initiation
GO:0006355 regulation of transcription, DNA-templated
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0010629 negative regulation of gene expression
GO:0016525 negative regulation of angiogenesis
GO:0042118 endothelial cell activation
GO:0045666 positive regulation of neuron differentiation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0065004 protein-DNA complex assembly
GO:1900746 regulation of vascular endothelial growth factor signaling pathway
Cellular Component: GO:0005634 nucleus
GO:0005667 transcription factor 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.FR748202 - Homo sapiens partial mRNA for transcription factor 4 isoform M (TCF4 gene).FR748206 - Homo sapiens partial mRNA for transcription factor 4 isoform E (TCF4 gene).FR748204 - Homo sapiens partial mRNA for transcription factor 4 isoform C (TCF4 gene).FR748203 - Homo sapiens partial mRNA for transcription factor 4 isoform L (TCF4 gene).JD283870 - Sequence 264894 from Patent EP1572962.JD101892 - Sequence 82916 from Patent EP1572962.
Other Names for This Gene
Alternate Gene Symbols: E9PH57, E9PH57_HUMAN, NM_001243226, NP_001230155UCSC ID: uc002lga.3RefSeq Accession: NM_001243226
Protein: E9PH57
CCDS: CCDS58631.1
GeneReviews for This Gene
GeneReviews article(s) related to gene TCF4:pitt-hopkins (Pitt-Hopkins Syndrome)
Gene Model Information
category:
coding
nonsense-mediated-decay:
no
RNA accession:
NM_001243226.1
exon count:
21 CDS single in 3' UTR:
no
RNA size:
8086
ORF size:
2322 CDS single in intron:
no
Alignment % ID:
100.00
txCdsPredict score:
4819.50 frame 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
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Methods, Credits, and Use Restrictions
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for details on how this gene model was made and data restrictions if any.