Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

SLC26A4

Reviewed June 2008

What is the official name of the SLC26A4 gene?

The official name of this gene is “solute carrier family 26 (anion exchanger), member 4.”

SLC26A4 is the gene's official symbol. The SLC26A4 gene is also known by other names, listed below.

What is the normal function of the SLC26A4 gene?

The SLC26A4 gene provides instructions for making a protein called pendrin. This protein transports negatively charged particles (ions), including chloride, iodide, and bicarbonate, across cell membranes. Pendrin is present in the kidneys, inner ear, and thyroid. The thyroid is a butterfly-shaped tissue at the base of the neck that releases hormones to help regulate growth and the rate of chemical reactions in the body (metabolism).

Although the function of pendrin is not fully understood, researchers have suggested particular roles for pendrin in various tissues. In the thyroid, pendrin probably transports iodide ions out of cells. The attachment of iodide ions to a protein called thyroglobulin is an important step in the production of thyroid hormones. In the inner ear, pendrin likely helps control the proper balance of charged particles such as chloride and bicarbonate ions. Maintaining the correct level of these ions is critical for the hearing process and for determining the amount of fluid that bathes the inner ear. The fluid level appears to be particularly important during development of the inner ear, and it may influence the shape of the bony structures such as the cochlea and vestibular aqueduct. The cochlea is a snail-shaped structure that helps process sound. The vestibular aqueduct is a bony canal that connects the inner ear with the brain cavity.

Does the SLC26A4 gene share characteristics with other genes?

The SLC26A4 gene belongs to a family of genes called SLC (solute carriers).

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 SLC26A4 gene related to health conditions?

nonsyndromic deafness - caused by mutations in the SLC26A4 gene

SLC26A4 mutations are associated with a form of nonsyndromic deafness (hearing loss without related signs and symptoms affecting other parts of the body) called DFNB4. People with DFNB4 deafness usually have an enlarged vestibular aqueduct.

It can be difficult to distinguish DFNB4 from a condition called Pendred syndrome. In addition to hearing loss and an enlarged vestibular aqueduct, people with Pendred syndrome often have an enlarged thyroid gland (goiter) and a malformed cochlea. Both conditions are caused by mutations in the SLC26A4 gene, and almost all of the mutations associated with Pendred syndrome have also been found to cause DFNB4. These two conditions are considered part of a spectrum of hearing loss with or without other features.

SLC26A4 mutations likely impair the activity of pendrin, which upsets the balance of ions and alters the levels of fluid in the inner ear. These changes presumably disrupt the development of structures in the inner ear and lead to hearing loss.

Pendred syndrome - caused by mutations in the SLC26A4 gene

Researchers have identified more than 60 mutations in the SLC26A4 gene in people with Pendred syndrome. Some of these mutations change single protein building blocks (amino acids) used to make pendrin. Certain mutations occur more frequently in particular populations. For example, an SLC26A4 mutation common in the Japanese population replaces the amino acid histidine with the amino acid arginine at position 723 in the pendrin protein (written as His723Arg). Among Northern Europeans, common mutations in the SLC26A4 gene replace the amino acid threonine with the amino acid proline at protein position 416 (Thr416Pro) or replace the amino acid leucine with proline at position 236 (Leu236Pro). Other types of mutations alter the SLC26A4 gene by deleting or adding a small amount of DNA. These deletions and additions probably create a premature stop signal in the instructions for making pendrin. As a result, an abnormally small protein is made.

Mutations in the SLC26A4 gene likely impair pendrin activity, disrupting ion transport. In the thyroid, disrupted transport prevents iodide ions from binding effectively to thyroglobulin. The thyroid tissue may enlarge to compensate for the perceived lack of iodine. In the inner ear, impaired pendrin activity probably upsets the balance of ions and alters the levels of fluid. These changes presumably disrupt the development of structures in the inner ear and lead to hearing loss.

Where is the SLC26A4 gene located?

Cytogenetic Location: 7q31

Molecular Location on chromosome 7: base pairs 107,660,634 to 107,717,808

The SLC26A4 gene is located on the long (q) arm of chromosome 7 at position 31.

The SLC26A4 gene is located on the long (q) arm of chromosome 7 at position 31.

More precisely, the SLC26A4 gene is located from base pair 107,660,634 to base pair 107,717,808 on chromosome 7.

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 SLC26A4?

You and your healthcare professional may find the following resources about SLC26A4 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 SLC26A4 gene or gene products?

  • deafness, autosomal recessive 4
  • PDS
  • pendrin
  • S26A4_HUMAN
  • solute carrier family 26, member 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 SLC26A4?

acids ; amino acid ; anion ; arginine ; autosomal ; autosomal recessive ; bicarbonate ; carrier ; cell ; charged particles ; chloride ; cochlea ; DNA ; gene ; goiter ; histidine ; iodine ; ions ; ion transport ; leucine ; metabolism ; mutation ; population ; proline ; protein ; recessive ; solute ; spectrum ; syndrome ; threonine ; thyroglobulin ; thyroid ; thyroid hormones ; tissue ; vestibular aqueduct

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

References

  • Albert S, Blons H, Jonard L, Feldmann D, Chauvin P, Loundon N, Sergent-Allaoui A, Houang M, Joannard A, Schmerber S, Delobel B, Leman J, Journel H, Catros H, Dollfus H, Eliot MM, David A, Calais C, Drouin-Garraud V, Obstoy MF, Tran Ba Huy P, Lacombe D, Duriez F, Francannet C, Bitoun P, Petit C, Garabédian EN, Couderc R, Marlin S, Denoyelle F. SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet. 2006 Jun;14(6):773-9. (http://www.ncbi.nlm.nih.gov/pubmed/16570074?dopt=Abstract)
  • Blons H, Feldmann D, Duval V, Messaz O, Denoyelle F, Loundon N, Sergout-Allaoui A, Houang M, Duriez F, Lacombe D, Delobel B, Leman J, Catros H, Journel H, Drouin-Garraud V, Obstoy MF, Toutain A, Oden S, Toublanc JE, Couderc R, Petit C, Garabédian EN, Marlin S. Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity. Clin Genet. 2004 Oct;66(4):333-40. (http://www.ncbi.nlm.nih.gov/pubmed/15355436?dopt=Abstract)
  • Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE, Karniski LP, Sheffield VC, Smith RJ. Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat. 2001 May;17(5):403-11. (http://www.ncbi.nlm.nih.gov/pubmed/11317356?dopt=Abstract)
  • Dawson PA, Markovich D. Pathogenetics of the human SLC26 transporters. Curr Med Chem. 2005;12(4):385-96. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15720248?dopt=Abstract)
  • Iwasaki S, Tsukamoto K, Usami S, Misawa K, Mizuta K, Mineta H. Association of SLC26A4 mutations with clinical features and thyroid function in deaf infants with enlarged vestibular aqueduct. J Hum Genet. 2006;51(9):805-10. Epub 2006 Aug 19. (http://www.ncbi.nlm.nih.gov/pubmed/16924389?dopt=Abstract)
  • Li XC, Everett LA, Lalwani AK, Desmukh D, Friedman TB, Green ED, Wilcox ER. A mutation in PDS causes non-syndromic recessive deafness. Nat Genet. 1998 Mar;18(3):215-7. (http://www.ncbi.nlm.nih.gov/pubmed/9500541?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5172)
  • Park HJ, Shaukat S, Liu XZ, Hahn SH, Naz S, Ghosh M, Kim HN, Moon SK, Abe S, Tukamoto K, Riazuddin S, Kabra M, Erdenetungalag R, Radnaabazar J, Khan S, Pandya A, Usami SI, Nance WE, Wilcox ER, Riazuddin S, Griffith AJ. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet. 2003 Apr;40(4):242-8. (http://www.ncbi.nlm.nih.gov/pubmed/12676893?dopt=Abstract)
  • Pryor SP, Madeo AC, Reynolds JC, Sarlis NJ, Arnos KS, Nance WE, Yang Y, Zalewski CK, Brewer CC, Butman JA, Griffith AJ. SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities. J Med Genet. 2005 Feb;42(2):159-65. (http://www.ncbi.nlm.nih.gov/pubmed/15689455?dopt=Abstract)
  • Reardon W, OMahoney CF, Trembath R, Jan H, Phelps PD. Enlarged vestibular aqueduct: a radiological marker of pendred syndrome, and mutation of the PDS gene. QJM. 2000 Feb;93(2):99-104. (http://www.ncbi.nlm.nih.gov/pubmed/10700480?dopt=Abstract)
  • Scott DA, Wang R, Kreman TM, Sheffield VC, Karniski LP. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet. 1999 Apr;21(4):440-3. (http://www.ncbi.nlm.nih.gov/pubmed/10192399?dopt=Abstract)
  • Suzuki H, Oshima A, Tsukamoto K, Abe S, Kumakawa K, Nagai K, Satoh H, Kanda Y, Iwasaki S, Usami S. Clinical characteristics and genotype-phenotype correlation of hearing loss patients with SLC26A4 mutations. Acta Otolaryngol. 2007 Dec;127(12):1292-7. (http://www.ncbi.nlm.nih.gov/pubmed/17851929?dopt=Abstract)
  • Wilcox ER, Everett LA, Li XC, Lalwani AK, Green ED. The PDS gene, Pendred syndrome and non-syndromic deafness DFNB4. Adv Otorhinolaryngol. 2000;56:145-51. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10868226?dopt=Abstract)
  • Wu CC, Chen PJ, Hsu CJ. Specificity of SLC26A4 mutations in the pathogenesis of inner ear malformations. Audiol Neurootol. 2005 Jul-Aug;10(4):234-42. Epub 2005 May 18. (http://www.ncbi.nlm.nih.gov/pubmed/15905611?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: June 2008
Published: December 16, 2014