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    Topic review

    SLC5A5 Gene

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    Submitted by: Karina Chen
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    solute carrier family 5 member 5

    1. Normal Function

    The SLC5A5 gene provides instructions for making a protein called sodium (Na)-iodide symporter or NIS. This protein transports iodide, a negatively charged version of iodine, into cells of certain tissues. The NIS protein is found primarily in the thyroid gland, a butterfly-shaped tissue in the lower neck. The thyroid gland produces and releases iodide-containing thyroid hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). The NIS protein supports an efficient system that ensures iodine from the diet accumulates in the thyroid gland for the production of thyroid hormones. This system depends on the NIS protein being positioned in the cell membrane, so it can transport iodide from the bloodstream into particular thyroid cells called follicular cells.

    In addition to the thyroid gland, the NIS protein is found in breast tissue during milk production (lactation), ovaries, salivary glands, certain stomach cells (parietal cells), tear glands (lacrimal glands), and a part of the brain called the choroid plexus. During lactation, the NIS protein transports iodide into the milk to supply breast-fed infants with this critical component of thyroid hormones.

    2. Health Conditions Related to Genetic Changes

    2.1. Congenital hypothyroidism

    Several SLC5A5 gene mutations have been identified in people with congenital hypothyroidism, a condition characterized by abnormally low levels of thyroid hormones starting from birth. About half of these mutations delete part of the SLC5A5 gene or disrupt protein production, resulting in an abnormally small, nonfunctional protein. The remaining mutations change one of the building blocks (amino acids) used to make the NIS protein. Some amino acid substitutions prevent the NIS protein from being positioned in the cell membrane, disabling iodide transport. Other amino acid substitutions do not affect the membrane location of the NIS protein but change the protein's 3-dimensional shape, which impairs its function.

    SLC5A5 gene mutations reduce or prevent iodide transport. As a result, the thyroid gland cannot accumulate iodide efficiently, which decreases the production of thyroid hormones. The signs and symptoms of congenital hypothyroidism associated with these gene mutations range from mild to severe depending on the level of hormone production remaining. In many cases, the thyroid gland is enlarged (goiter) in an attempt to compensate for reduced hormone production. Because cases caused by SLC5A5 gene mutations are due to a disruption of thyroid hormone synthesis, they are classified as thyroid dyshormonogenesis.

    3. Other Names for This Gene

    • NIS
    • SC5A5_HUMAN
    • sodium-iodide symporter
    • solute carrier family 5 (sodium/iodide cotransporter), member 5

    This entry is adapted from https://medlineplus.gov/genetics/gene/slc5a5

    References

    1. De La Vieja A, Dohan O, Levy O, Carrasco N. Molecular analysis of thesodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology.Physiol Rev. 2000 Jul;80(3):1083-105. Review.
    2. Dohán O, Carrasco N. Advances in Na(+)/I(-) symporter (NIS) research in thethyroid and beyond. Mol Cell Endocrinol. 2003 Dec 31;213(1):59-70. Review.
    3. Dohán O, De la Vieja A, Paroder V, Riedel C, Artani M, Reed M, Ginter CS,Carrasco N. The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr Rev. 2003 Feb;24(1):48-77. Review.
    4. Nicola JP, Nazar M, Serrano-Nascimento C, Goulart-Silva F, Sobrero G, Testa G,Nunes MT, Muñoz L, Miras M, Masini-Repiso AM. Iodide transport defect: functionalcharacterization of a novel mutation in the Na+/I- symporter 5'-untranslatedregion in a patient with congenital hypothyroidism. J Clin Endocrinol Metab. 2011Jul;96(7):E1100-7. doi: 10.1210/jc.2011-0349.
    5. Pohlenz J, Refetoff S. Mutations in the sodium/iodide symporter (NIS) gene as a cause for iodide transport defects and congenital hypothyroidism. Biochimie.1999 May;81(5):469-76. Review.
    6. Spitzweg C, Morris JC. Genetics and phenomics of hypothyroidism and goiter dueto NIS mutations. Mol Cell Endocrinol. 2010 Jun 30;322(1-2):56-63. doi:10.1016/j.mce.2010.02.007.
    7. Spitzweg C, Morris JC. The sodium iodide symporter: its pathophysiological andtherapeutic implications. Clin Endocrinol (Oxf). 2002 Nov;57(5):559-74. Review.
    8. Szinnai G, Kosugi S, Derrien C, Lucidarme N, David V, Czernichow P, Polak M.Extending the clinical heterogeneity of iodide transport defect (ITD): a novelmutation R124H of the sodium/iodide symporter gene and review ofgenotype-phenotype correlations in ITD. J Clin Endocrinol Metab. 2006Apr;91(4):1199-204.
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