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SLC26A4 gene
URL of this page: https://medlineplus.gov/genetics/gene/slc26a4/

SLC26A4 gene

solute carrier family 26 member 4

Normal Function

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 produced in several organs and tissues, particularly the inner ear and thyroid gland.

The thyroid gland is a butterfly-shaped organ at the base of the neck that releases hormones to help regulate growth and the rate of chemical reactions in the body (metabolism). In the thyroid, pendrin is believed to transport iodide ions out of certain cells. Iodide is needed for the normal production of thyroid hormones.

In the inner ear, pendrin likely helps control the proper balance of ions, including chloride and bicarbonate. Maintaining the proper levels of these ions appears to be particularly important during development of the inner ear, and it may influence the shape of 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 inside of the skull.

Pendrin is also found in other tissues, including the kidneys, liver, and lining of the airways. Researchers are studying the role of pendrin's ion transport function in these tissues.

Health Conditions Related to Genetic Changes

Congenital hypothyroidism

MedlinePlus Genetics provides information about Congenital hypothyroidism

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Nonsyndromic hearing loss

Dozens of SLC26A4 gene mutations have been identified in people with nonsyndromic hearing loss, which is loss of hearing that is not associated with signs and symptoms affecting other parts of the body. Mutations in this gene cause a form of nonsyndromic hearing loss called DFNB4. This form of hearing loss can either be present before a child learns to speak (prelingual) or begin after a child learns to speak (postlingual). Most people with DFNB4 also have an unusually large vestibular aqueduct (enlarged vestibular aqueduct, or EVA).

Mutations in the SLC26A4 gene impair or eliminate the activity of pendrin, which upsets the balance of ions in the inner ear. These changes presumably affect the development of structures in the inner ear, including the cochlea and vestibular aqueduct. Studies suggest that the changes in ion levels also lead to the loss of sensory cells in the inner ear that are needed for hearing.

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Pendred syndrome

Researchers have identified more than 150 mutations in the SLC26A4 gene in people with Pendred syndrome. This condition is characterized by enlargement of the thyroid gland (called a goiter), hearing loss, and other abnormalities of the inner ear, including an enlarged vestibular aqueduct.

Some of the SLC26A4 gene mutations change single protein building blocks (amino acids) used to make pendrin. Other mutations add or delete a small amount of DNA in the SLC26A4 gene. All of these genetic changes impair or eliminate the activity of pendrin, which disrupts ion transport. In the thyroid, the disrupted ion transport prevents iodide ions from being available for thyroid hormone production. To compensate for the perceived lack of iodide, the thyroid tissue enlarges to form a goiter. In the inner ear, impaired pendrin activity alters the balance of ions, which presumably affects the development of structures including the cochlea and vestibular aqueduct. Studies suggest that the changes in ion levels also lead to the loss of sensory cells in the inner ear that are needed for hearing.

Because their signs and symptoms overlap, it can be difficult to distinguish Pendred syndrome from nonsyndromic hearing loss (DFNB4, described above). Many of the SLC26A4 gene mutations associated with Pendred syndrome have also been found to cause DFNB4. Mutations in this gene can also cause other thyroid abnormalities; in a small number of people, SLC26A4 gene mutations have been associated with an abnormally small thyroid gland (thyroid hypoplasia) that causes a loss of thyroid function from birth (congenital hypothyroidism). It is unclear whether Pendred syndrome, DFNB4, and thyroid hypoplasia caused by SLC26A4 gene mutations are best considered as separate disorders or as a spectrum of related signs and symptoms.

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Age-related hearing loss

MedlinePlus Genetics provides information about Age-related hearing loss

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Hashimoto's disease

MedlinePlus Genetics provides information about Hashimoto's disease

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Other Names for This Gene

  • PDS
  • pendrin
  • S26A4_HUMAN
  • solute carrier family 26 (anion exchanger), member 4
  • solute carrier family 26, member 4

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

  • 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, Garabedian 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. doi: 10.1038/sj.ejhg.5201611. Citation on PubMed
  • Dossena S, Rodighiero S, Vezzoli V, Nofziger C, Salvioni E, Boccazzi M, Grabmayer E, Botta G, Meyer G, Fugazzola L, Beck-Peccoz P, Paulmichl M. Functional characterization of wild-type and mutated pendrin (SLC26A4), the anion transporter involved in Pendred syndrome. J Mol Endocrinol. 2009 Sep;43(3):93-103. doi: 10.1677/JME-08-0175. Epub 2009 Jul 16. Citation on PubMed
  • Fang Y, Gu M, Wang C, Suo F, Wang G, Xia Y. GJB2 as Well as SLC26A4 Gene Mutations are Prominent Causes for Congenital Deafness. Cell Biochem Biophys. 2015 Sep;73(1):41-4. doi: 10.1007/s12013-015-0562-3. Citation on PubMed
  • Ito T, Choi BY, King KA, Zalewski CK, Muskett J, Chattaraj P, Shawker T, Reynolds JC, Butman JA, Brewer CC, Wangemann P, Alper SL, Griffith AJ. SLC26A4 genotypes and phenotypes associated with enlargement of the vestibular aqueduct. Cell Physiol Biochem. 2011;28(3):545-52. doi: 10.1159/000335119. Epub 2011 Nov 18. Citation on PubMed or Free article on PubMed Central
  • Kopp P. Mutations in the Pendred Syndrome (PDS/SLC26A) gene: an increasingly complex phenotypic spectrum from goiter to thyroid hypoplasia. J Clin Endocrinol Metab. 2014 Jan;99(1):67-9. doi: 10.1210/jc.2013-4319. No abstract available. Citation on PubMed
  • Kuhnen P, Turan S, Frohler S, Guran T, Abali S, Biebermann H, Bereket A, Gruters A, Chen W, Krude H. Identification of PENDRIN (SLC26A4) mutations in patients with congenital hypothyroidism and "apparent" thyroid dysgenesis. J Clin Endocrinol Metab. 2014 Jan;99(1):E169-76. doi: 10.1210/jc.2013-2619. Epub 2013 Dec 20. Citation on PubMed
  • 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. doi: 10.1038/ng0398-215. No abstract available. Citation on PubMed
  • 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. doi: 10.1038/7783. Citation on PubMed
  • Tsukada K, Nishio SY, Hattori M, Usami S. Ethnic-specific spectrum of GJB2 and SLC26A4 mutations: their origin and a literature review. Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:61S-76S. doi: 10.1177/0003489415575060. Citation on PubMed

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