TCF4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTCF4, E2-2, ITF-2, ITF2, PTHS, SEF-2, SEF2, SEF2-1, SEF2-1A, SEF2-1B, SEF2-1D, TCF-4, bHLHb19, FECD3, transcription factor 4, CDG2T
External IDsOMIM: 602272 MGI: 98506 HomoloGene: 2407 GeneCards: TCF4
Orthologs
SpeciesHumanMouse
Entrez

6925

21413

Ensembl

ENSG00000196628

ENSMUSG00000053477

UniProt

P15884

Q60722

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 18: 55.22 – 55.66 MbChr 18: 69.34 – 69.69 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transcription factor 4 (TCF-4) also known as immunoglobulin transcription factor 2 (ITF-2) is a protein that in humans is encoded by the TCF4 gene located on chromosome 18q21.2.[5]

Function

TCF4 proteins act as transcription factors which will bind to the immunoglobulin enhancer mu-E5/kappa-E2 motif. TCF4 activates transcription by binding to the E-box (5’-CANNTG-3’) found usually on SSTR2-INR, or somatostatin receptor 2 initiator element. TCF4 is primarily involved in neurological development of the fetus during pregnancy by initiating neural differentiation by binding to DNA. It is found in the central nervous system, somites, and gonadal ridge during early development. Later in development it will be found in the thyroid, thymus, and kidneys while in adulthood TCF4 it is found in lymphocytes, muscles, mature neurons, and gastrointestinal system.[6][7][8]


Clinical significance

Mutations in TCF4 cause Pitt-Hopkins Syndrome (PTHS). These mutations cause TCF4 proteins to not bind to DNA properly and control the differentiation of the nervous system. It has been suggested that TCF4 loss-of-function leads to decreased Wnt signaling and, consequently, a reduced neural progenitor proliferation.[9] In most cases that have been studied, the mutations were de novo, meaning it was a new mutation not found in other family members of the patient. Common symptoms of Pitt-Hopkins Syndrome include a wide mouth, gastrointestinal problems, developmental delay of fine motor skills, speech and breathing problems, epilepsy, and other brain defects.[10][11]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000196628 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000053477 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Henthorn P, McCarrick-Walmsley R, Kadesch T (February 1990). "Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor". Nucleic Acids Research. 18 (3): 678. doi:10.1093/nar/18.3.678. PMC 333500. PMID 2308860.
  6. ↑ de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, et al. (April 2009). "Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome". Human Mutation. 30 (4): 669–676. doi:10.1002/humu.20935. PMID 19235238. S2CID 25375730.
  7. ↑ Pscherer A, Dörflinger U, Kirfel J, Gawlas K, Rüschoff J, Buettner R, Schüle R (December 1996). "The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene". The EMBO Journal. 15 (23): 6680–6690. doi:10.1002/j.1460-2075.1996.tb01058.x. PMC 452492. PMID 8978694.
  8. ↑ D'Rozario M, Zhang T, Waddell EA, Zhang Y, Sahin C, Sharoni M, et al. (April 2016). "Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons". Cell Reports. 15 (2): 386–397. doi:10.1016/j.celrep.2016.03.034. PMC 4946342. PMID 27050508.
  9. ↑ Papes F, Camargo AP, de Souza JS, Carvalho VM, Szeto RA, LaMontagne E, et al. (May 2022). "Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content". Nature Communications. 13 (1): 2387. doi:10.1038/s41467-022-29942-w. PMC 9061776. PMID 35501322.
  10. ↑ Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N, et al. (May 2007). "Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction". American Journal of Human Genetics. 80 (5): 988–993. doi:10.1086/515582. PMC 1852736. PMID 17436254.
  11. ↑ Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, et al. (May 2007). "Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)". American Journal of Human Genetics. 80 (5): 994–1001. doi:10.1086/515583. PMC 1852727. PMID 17436255.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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