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For the Transcription factor 7-like 2 gene, also known as TCF4, see TCF7L2.
Available structures
PDB Ortholog search: PDBe RCSB
Aliases TCF4, E2-2, ITF-2, ITF2, PTHS, SEF-2, SEF2, SEF2-1, SEF2-1A, SEF2-1B, SEF2-1D, TCF-4, bHLHb19, FECD3, transcription factor 4
External IDs OMIM: 602272 MGI: 98506 HomoloGene: 2407 GeneCards: TCF4
Genetically Related Diseases
morbid obesity, schizophrenia, ulcerative colitis, sclerosing cholangitis, Fuchs' endothelial dystrophy[1]
Species Human Mouse
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC) Chr 18: 55.22 – 55.66 Mb Chr 18: 69.34 – 69.69 Mb
PubMed search [2] [3]
View/Edit Human View/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 18q21.1.[4]


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, and gastrointestinal system.[5][6]

Clinical significance[edit]

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. 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.[7][8]


  1. ^ "Diseases that are genetically associated with TCF4 view/edit references on wikidata". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ Henthorn P, McCarrick-Walmsley R, Kadesch T (Feb 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 333500Freely accessible. PMID 2308860. 
  5. ^ de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, et al. (Apr 2009). "Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome". Human Mutation. 30 (4): 669–76. doi:10.1002/humu.20935. PMID 19235238. 
  6. ^ Pscherer A, Dörflinger U, Kirfel J, Gawlas K, Rüschoff J, Buettner R, Schüle R (Dec 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): 6680–90. PMID 8978694. 
  7. ^ 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): 988–93. doi:10.1086/515582. PMID 17436254. 
  8. ^ 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 1852727Freely accessible. PMID 17436255. 

Further reading[edit]

External links[edit]

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