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POU3F4 gene
URL of this page: https://medlineplus.gov/genetics/gene/pou3f4/

POU3F4 gene

POU class 3 homeobox 4

Normal Function

The POU3F4 gene provides instructions for making a protein that helps regulate the activity of other genes. Proteins that perform this role are called transcription factors. 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 have two regions, one called the POU-specific domain and another called the POU homeodomain, that bind to the DNA of other genes.

The POU3F4 protein is involved in the development of cells within a snail-shaped structure called the cochlea in the inner ear. The cochlea converts sound waves into electrical nerve impulses, which are then transmitted to the brain. This process is critical for normal hearing.

Health Conditions Related to Genetic Changes

Nonsyndromic hearing loss

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants involving the POU3F4 gene cause nonsyndromic hearing loss, which is a partial or total loss of hearing that is not associated with other signs and symptoms.

Pathogenic variants in the POU3F4 gene cause a form of nonsyndromic hearing loss called DFNX2. 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 variants in genes on the X chromosome, which is one of the two sex chromosomes.

The signs and symptoms of DFNX2 differ in boys and girls. In boys, this form of hearing loss begins before the child learns to speak (prelingual), worsens over time, and usually involves abnormalities of both the inner ear and the middle ear (mixed hearing loss). Girls with DFNX2 tend to be less severely affected with hearing loss, which usually begins after the child learns to speak (postlingual).

The pathogenic variants in the POU3F4 gene that cause DFNX2 typically delete part of the gene or lead to the substitution of one protein building block (amino acid) for another in the POU3F4 protein. In some cases, variants have been found near the POU3F4 gene in the region of DNA that plays a role in regulating the activity of the POU3F4 gene. The variants that cause DFNX2 prevent cells from producing any POU3F4 protein or cause cells to produce an altered version of the protein. The lack of functional POU3F4 protein disrupts the development of structures in the ear, particularly the cochlea. This leads to nonsyndromic hearing loss.

More About This Health Condition

Other Names for This Gene

  • BRAIN-4
  • Brn-4
  • BRN4
  • DFN3
  • DFNX2
  • OTF9

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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  • Bitner-Glindzicz M, Turnpenny P, Hoglund P, Kaariainen 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. doi: 10.1093/hmg/4.8.1467. No abstract available. Citation on PubMed
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  • 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. doi: 10.1126/science.7839145. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • Prat Matifoll JA, Wilson M, Goetti R, Birman C, Bennett B, Peadon E, Prats-Uribe A, Prelog K. A Case Series of X-Linked Deafness-2 with Sensorineural Hearing Loss, Stapes Fixation, and Perilymphatic Gusher: MR Imaging and Clinical Features of Hypothalamic Malformations. AJNR Am J Neuroradiol. 2020 Jun;41(6):1087-1093. doi: 10.3174/ajnr.A6541. Epub 2020 May 14. Citation on PubMed
  • Song MH, Lee KY, Choi JY, Bok J, Kim UK. Nonsyndromic X-linked hearing loss. Front Biosci (Elite Ed). 2012 Jan 1;4(3):924-33. doi: 10.2741/E430. Citation on PubMed
  • Su Y, Gao X, Huang SS, Mao JN, Huang BQ, Zhao JD, Kang DY, Zhang X, Dai P. Clinical and molecular characterization of POU3F4 mutations in multiple DFNX2 Chinese families. BMC Med Genet. 2018 Sep 4;19(1):157. doi: 10.1186/s12881-018-0630-9. Citation on PubMed

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