POU3F4

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 genes called POU domain genes, all of which produce transcription factors. POU domain genes play a role in determining cell types in the central nervous system during early development. Each protein in the POU domain family has two regions, called the POU-specific domain and POU homeodomain, that bind to the DNA of other genes.

The POU3F4 gene is likely to be involved in the development of the middle and inner ear, and is also active in certain regions of the brain before birth. Researchers have not determined which genes are regulated by the POU3F4 protein.

nonsyndromic deafness - caused by mutations in the POU3F4 gene

Mutations in or near the POU3F4 gene cause a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFN3. This form of hearing loss usually involves abnormalities of both the inner and middle ear (mixed hearing loss). People who have surgery for this form of deafness are at high risk of a complication called a perilymphatic gusher. This complication causes a leakage of fluid from the inner ear that can result in severe dizziness and a total loss of hearing.

More than 15 POU3F4 mutations have been identified. Most of these genetic changes alter single protein building blocks (amino acids) in the POU3F4 protein or delete a small amount of genetic material from the gene. The mutations prevent cells from producing any POU3F4 protein or alter 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.

In some cases of DFN3, mutations have been found in a section of DNA near the POU3F4 gene. Researchers believe that this region may play a role in regulating POU3F4.