Human Gene TCF4 (uc010xdx.1) Description and Page Index
Description: Homo sapiens transcription factor 4 (TCF4), transcript variant 3, 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 chr18:52,889,562-53,253,336 Size: 363,775 Total Exon Count: 19 Strand: - Coding Region Position: hg19 chr18:52,895,456-53,252,583 Size: 357,128 Coding Exon Count: 17
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
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.
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.
schizophrenia Stefansson ,et al. 2009, Common variants conferring risk of schizophrenia, Nature 2009 460- 7256 : 744-7.
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.
ModBase Predicted Comparative 3D Structure on P15884
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.