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Genetics Home Reference: your guide to understanding genetic conditions
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TCF4

Reviewed May 2011

What is the official name of the TCF4 gene?

The official name of this gene is “transcription factor 4.”

TCF4 is the gene's official symbol. The TCF4 gene is also known by other names, listed below.

What is the normal function of the TCF4 gene?

The TCF4 gene provides instructions for making a gene that attaches (binds) to specific regions of DNA and helps control the activity of many other genes. On the basis of this action, the TCF4 protein is known as a transcription factor. The TCF4 protein is part of a group of proteins known as E-proteins. E-proteins each bind with another identical or similar protein and then bind to a specific sequence of DNA known as an E-box. E-proteins are involved in many aspects of development.

The TCF4 protein is found in the brain, muscles, lungs, and heart. This protein also appears to be active (expressed) in various tissues before birth. The TCF4 protein plays a role in the maturation of cells to carry out specific functions (cell differentiation) and the self-destruction of cells (apoptosis).

Does the TCF4 gene share characteristics with other genes?

The TCF4 gene belongs to a family of genes called bHLH (basic helix-loop-helix).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the TCF4 gene related to health conditions?

Pitt-Hopkins syndrome - caused by mutations in the TCF4 gene

At least 50 mutations in the TCF4 gene have been found to cause Pitt-Hopkins syndrome, a condition characterized by severe intellectual disability and breathing problems. Some mutations delete a few building blocks of DNA (nucleotides) within the TCF4 gene, while other mutations delete the TCF4 gene as well as a number of genes that surround it. Still other TCF4 gene mutations replace single nucleotides. The size of the mutation does not appear to affect the severity of the condition; people with large deletions and those with single nucleotide changes seem to have similar signs and symptoms.

TCF4 gene mutations disrupt the protein's ability to bind to DNA and control the activity of certain genes. These gene mutations typically do not affect the TCF4 protein's ability to bind to other proteins. The TCF4 protein's inability to bind to DNA and control the activity of certain genes, particularly those genes involved in nervous system development and function, contributes to the signs and symptoms of Pitt-Hopkins syndrome. It is also likely that the loss of the normal proteins that are attached to the nonfunctional TCF4 proteins contribute to the features of this condition.

Where is the TCF4 gene located?

Cytogenetic Location: 18q21.1

Molecular Location on chromosome 18: base pairs 55,222,330 to 55,635,956

The TCF4 gene is located on the long (q) arm of chromosome 18 at position 21.1.

The TCF4 gene is located on the long (q) arm of chromosome 18 at position 21.1.

More precisely, the TCF4 gene is located from base pair 55,222,330 to base pair 55,635,956 on chromosome 18.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about TCF4?

You and your healthcare professional may find the following resources about TCF4 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the TCF4 gene or gene products?

  • bHLHb19
  • class B basic helix-loop-helix protein 19
  • E2-2
  • immunoglobulin transcription factor 2
  • ITF2
  • ITF-2
  • ITF2_HUMAN
  • SEF2
  • SEF-2
  • TCF-4

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding TCF4?

apoptosis ; cell ; class ; differentiation ; disability ; DNA ; expressed ; gene ; immunoglobulin ; mutation ; nervous system ; nucleotide ; protein ; syndrome ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N, Plouin P, Carter NP, Lyonnet S, Munnich A, Colleaux L. 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. Am J Hum Genet. 2007 May;80(5):988-93. Epub 2007 Mar 23. (http://www.ncbi.nlm.nih.gov/pubmed/17436254?dopt=Abstract)
  • de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, Soufflet C, Picard C, Durandy A, Dobbie A, Heron D, Isidor B, Motte J, Newburry-Ecob R, Pasquier L, Tardieu M, Viot G, Jaubert F, Munnich A, Colleaux L, Vekemans M, Etchevers H, Lyonnet S, Amiel J. Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. Hum Mutat. 2009 Apr;30(4):669-76. doi: 10.1002/humu.20935. (http://www.ncbi.nlm.nih.gov/pubmed/19235238?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6925)
  • Takano K, Lyons M, Moyes C, Jones J, Schwartz CE. Two percent of patients suspected of having Angelman syndrome have TCF4 mutations. Clin Genet. 2010 Sep;78(3):282-8. doi: 10.1111/j.1399-0004.2010.01380.x. Epub 2010 Feb 10. (http://www.ncbi.nlm.nih.gov/pubmed/20184619?dopt=Abstract)
  • OMIM: TRANSCRIPTION FACTOR 4 (http://omim.org/entry/602272)
  • Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, Reardon W, Saraiva J, Cabral A, Gohring I, Devriendt K, de Ravel T, Bijlsma EK, Hennekam RC, Orrico A, Cohen M, Dreweke A, Reis A, Nurnberg P, Rauch A. Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). Am J Hum Genet. 2007 May;80(5):994-1001. Epub 2007 Mar 23. (http://www.ncbi.nlm.nih.gov/pubmed/17436255?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2011
Published: December 22, 2014