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Genetics Home Reference: your guide to understanding genetic conditions
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POU3F4

Reviewed February 2016

What is the official name of the POU3F4 gene?

The official name of this gene is “POU class 3 homeobox 4.”

POU3F4 is the gene's official symbol. The POU3F4 gene is also known by other names, listed below.

What is the normal function of the POU3F4 gene?

The POU3F4 gene provides instructions for making a protein that helps regulate the activity of other genes. Based on this role, the protein is called a transcription factor. The POU3F4 gene is part of a larger family of transcription factor genes called POU domain genes. These genes play a role in determining cell types in the brain and spinal cord (the central nervous system) during early development. The proteins produced from genes in the POU domain family each include two regions, called the POU-specific domain and POU homeodomain, that bind to the DNA of other genes.

The POU3F4 protein is likely to be involved in the development of the middle and inner ear, and it is also active in certain regions of the brain before birth. Researchers are working to determine which genes are regulated by this protein.

Does the POU3F4 gene share characteristics with other genes?

The POU3F4 gene belongs to a family of genes called homeobox (homeoboxes).

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 POU3F4 gene related to health conditions?

nonsyndromic hearing loss - caused by mutations in the POU3F4 gene

Mutations involving the POU3F4 gene cause nonsyndromic hearing loss, which is a loss of hearing that is not associated with other signs and symptoms. Mutations in this gene cause a form of hearing loss designated as DFNX2, sometimes also known as Nance deafness. DFNX2 is the most common type of X-linked nonsyndromic hearing loss, accounting for about half of all cases. X-linked conditions are caused by mutations in genes on the X chromosome, which is one of the two sex chromosomes.

The signs and symptoms of DFNX2 differ in males and females. In males, this form of hearing loss begins before the child learns to speak (prelingual), becomes more severe over time, and usually involves abnormalities of both the inner ear and the middle ear (mixed hearing loss). In the middle ear, one of the small bones (the stapes) cannot move normally, which interferes with hearing. This characteristic sign of DFNX2 is called stapes fixation. During surgery to repair this abnormality, affected males are at high risk of a complication called a perilymphatic gusher, which is a leakage of fluid from the inner ear that can result in a permanent, total loss of hearing. Females with POU3F4 gene mutations tend to be less severely affected, with little or no hearing loss and no apparent middle ear abnormalities. When hearing loss occurs, it usually begins after the child learns to speak (postlingual).

More than 50 POU3F4 gene mutations have been found to cause DFNX2. Many of these genetic changes alter single protein building blocks (amino acids) in the POU3F4 protein or delete part or all of the POU3F4 gene. In some cases, mutations have been found in DNA near the POU3F4 gene. Researchers believe that this DNA may play a role in regulating the POU3F4 gene. Mutations in or near this gene prevent cells from producing any POU3F4 protein or impair regions of the protein that are critical for binding to DNA. A lack of functional POU3F4 protein probably disrupts the normal development of structures in the middle and inner ear, leading to hearing loss.

Where is the POU3F4 gene located?

Cytogenetic Location: Xq21.1

Molecular Location on the X chromosome: base pairs 83,508,261 to 83,509,767

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/5456))

The POU3F4 gene is located on the long (q) arm of the X chromosome at position 21.1.

The POU3F4 gene is located on the long (q) arm of the X chromosome at position 21.1.

More precisely, the POU3F4 gene is located from base pair 83,508,261 to base pair 83,509,767 on the X chromosome.

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 POU3F4?

You and your healthcare professional may find the following resources about POU3F4 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 POU3F4 gene or gene products?

  • BRAIN-4
  • brain-specific homeobox/POU domain protein 4
  • BRN4
  • Brn-4
  • DFN3
  • DFNX2
  • OTF9
  • PO34_HUMAN

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 POU3F4?

acids ; cell ; central nervous system ; chromosome ; class ; complication ; DNA ; domain ; gene ; homeobox ; homeodomain ; nervous system ; postlingual ; prelingual ; protein ; sex chromosomes ; sign ; stapes ; surgery ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References

  • Bademci G, Lasisi A, Yariz KO, Montenegro P, Menendez I, Vinueza R, Paredes R, Moreta G, Subasioglu A, Blanton S, Fitoz S, Incesulu A, Sennaroglu L, Tekin M. Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations. BMC Med Genet. 2015 Feb 25;16:9. doi: 10.1186/s12881-015-0149-2. (http://www.ncbi.nlm.nih.gov/pubmed/25928534?dopt=Abstract)
  • Bitner-Glindzicz M, Turnpenny P, Höglund P, Kääriäinen H, Sankila EM, van der Maarel SM, de Kok YJ, Ropers HH, Cremers FP, Pembrey M, et al. Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3. Hum Mol Genet. 1995 Aug;4(8):1467-9. (http://www.ncbi.nlm.nih.gov/pubmed/7581392?dopt=Abstract)
  • de Kok YJ, van der Maarel SM, Bitner-Glindzicz M, Huber I, Monaco AP, Malcolm S, Pembrey ME, Ropers HH, Cremers FP. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4. Science. 1995 Feb 3;267(5198):685-8. (http://www.ncbi.nlm.nih.gov/pubmed/7839145?dopt=Abstract)
  • Lee HK, Song MH, Kang M, Lee JT, Kong KA, Choi SJ, Lee KY, Venselaar H, Vriend G, Lee WS, Park HJ, Kwon TK, Bok J, Kim UK. Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein. Physiol Genomics. 2009 Nov 6;39(3):195-201. doi: 10.1152/physiolgenomics.00100.2009. Epub 2009 Aug 11. (http://www.ncbi.nlm.nih.gov/pubmed/19671658?dopt=Abstract)
  • Marlin S, Moizard MP, David A, Chaissang N, Raynaud M, Jonard L, Feldmann D, Loundon N, Denoyelle F, Toutain A. Phenotype and genotype in females with POU3F4 mutations. Clin Genet. 2009 Dec;76(6):558-63. doi: 10.1111/j.1399-0004.2009.01215.x. (http://www.ncbi.nlm.nih.gov/pubmed/19930154?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5456)
  • Parzefall T, Shivatzki S, Lenz DR, Rathkolb B, Ushakov K, Karfunkel D, Shapira Y, Wolf M, Mohr M, Wolf E, Sabrautzki S, de Angelis MH, Frydman M, Brownstein Z, Avraham KB. Cytoplasmic mislocalization of POU3F4 due to novel mutations leads to deafness in humans and mice. Hum Mutat. 2013 Aug;34(8):1102-10. doi: 10.1002/humu.22339. Epub 2013 May 8. (http://www.ncbi.nlm.nih.gov/pubmed/23606368?dopt=Abstract)
  • Song MH, Lee KY, Choi JY, Bok J, Kim UK. Nonsyndromic X-linked hearing loss. Front Biosci (Elite Ed). 2012 Jan 1;4:924-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22201925?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: February 2016
Published: February 8, 2016