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Genetics Home Reference: your guide to understanding genetic conditions
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OTOF

Reviewed November 2006

What is the official name of the OTOF gene?

The official name of this gene is “otoferlin.”

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

What is the normal function of the OTOF gene?

The OTOF gene provides instructions for making a protein called otoferlin. This protein is present in the brain and the cochlea, which is a snail-shaped structure in the inner ear that helps process sound. Although the exact function of otoferlin is uncertain, it appears to be essential for normal hearing. Researchers believe that otoferlin may play a role in releasing chemical signals (neurotransmitters) from nerve cells that are involved in hearing. This process is dependent on the concentration of calcium within the cell. The otoferlin protein has several regions called C2 domains that bind to calcium and use it to interact with other molecules.

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

nonsyndromic deafness - caused by mutations in the OTOF gene

At least 16 mutations in the OTOF gene have been identified in people with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB9. People with these mutations have a type of hearing loss called auditory neuropathy, which occurs when sound is not transmitted properly from the inner ear to the brain.

Some mutations in the OTOF gene result in the production of an abnormally small, nonfunctional version of otoferlin or prevent cells from making any of this protein. Other genetic changes probably alter the 3-dimensional structure of otoferlin, which impairs its ability to bind to calcium.

A particular OTOF mutation is a common cause of nonsyndromic deafness in the Spanish population. This mutation replaces one amino acid building block, glutamine, with a signal that stops protein production prematurely at position 829 in the otoferlin protein (written as Gln829Ter or Q829X). The Q829X mutation causes an abnormally short version of otoferlin to be made, which disrupts the protein's function and leads to hearing loss.

Where is the OTOF gene located?

Cytogenetic Location: 2p23.1

Molecular Location on chromosome 2: base pairs 26,457,202 to 26,558,697

The OTOF gene is located on the short (p) arm of chromosome 2 at position 23.1.

The OTOF gene is located on the short (p) arm of chromosome 2 at position 23.1.

More precisely, the OTOF gene is located from base pair 26,457,202 to base pair 26,558,697 on chromosome 2.

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 OTOF?

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

  • DFNB6
  • DFNB9
  • FER1L2
  • Fer-1 like protein 2
  • NSRD9
  • OTOF_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 OTOF?

amino acid ; auditory ; autosomal ; autosomal recessive ; calcium ; cell ; cochlea ; gene ; glutamine ; mutation ; neuropathy ; neurotransmitters ; population ; protein ; recessive ; vesicle

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

References

  • Migliosi V, Modamio-Høybjør S, Moreno-Pelayo MA, Rodríguez-Ballesteros M, Villamar M, Tellería D, Menéndez I, Moreno F, Del Castillo I. Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss. J Med Genet. 2002 Jul;39(7):502-6. (http://www.ncbi.nlm.nih.gov/pubmed/12114484?dopt=Abstract)
  • Mirghomizadeh F, Pfister M, Apaydin F, Petit C, Kupka S, Pusch CM, Zenner HP, Blin N. Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness. Neurobiol Dis. 2002 Jul;10(2):157-64. (http://www.ncbi.nlm.nih.gov/pubmed/12127154?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/9381)
  • Rodríguez-Ballesteros M, del Castillo FJ, Martín Y, Moreno-Pelayo MA, Morera C, Prieto F, Marco J, Morant A, Gallo-Terán J, Morales-Angulo C, Navas C, Trinidad G, Tapia MC, Moreno F, del Castillo I. Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF). Hum Mutat. 2003 Dec;22(6):451-6. (http://www.ncbi.nlm.nih.gov/pubmed/14635104?dopt=Abstract)
  • Tekin M, Akcayoz D, Incesulu A. A novel missense mutation in a C2 domain of OTOF results in autosomal recessive auditory neuropathy. Am J Med Genet A. 2005 Sep 15;138(1):6-10. (http://www.ncbi.nlm.nih.gov/pubmed/16097006?dopt=Abstract)
  • Varga R, Avenarius MR, Kelley PM, Keats BJ, Berlin CI, Hood LJ, Morlet TG, Brashears SM, Starr A, Cohn ES, Smith RJ, Kimberling WJ. OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. J Med Genet. 2006 Jul;43(7):576-81. Epub 2005 Dec 21. (http://www.ncbi.nlm.nih.gov/pubmed/16371502?dopt=Abstract)
  • Varga R, Kelley PM, Keats BJ, Starr A, Leal SM, Cohn E, Kimberling WJ. Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene. J Med Genet. 2003 Jan;40(1):45-50. (http://www.ncbi.nlm.nih.gov/pubmed/12525542?dopt=Abstract)
  • Yasunaga S, Grati M, Chardenoux S, Smith TN, Friedman TB, Lalwani AK, Wilcox ER, Petit C. OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9. Am J Hum Genet. 2000 Sep;67(3):591-600. Epub 2000 Jul 19. (http://www.ncbi.nlm.nih.gov/pubmed/10903124?dopt=Abstract)
  • Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet. 1999 Apr;21(4):363-9. (http://www.ncbi.nlm.nih.gov/pubmed/10192385?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: November 2006
Published: December 16, 2014