Gene Associated With Multinodular Goiter: NIS (SLC5A5) = sodium-iodide symporter gene

a.    The normal function of the SLC5A5 gene

      The SLC5A5 gene provides instructions for making a protein called sodium-iodide symporter or NIS. In certain tissues, this protein facilitates the uptake of iodide (a negatively charged version of iodine). 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 a remarkably 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.

b.    The SLC5A5 gene share characteristics with other genes

       The SLC5A5 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.

c.    The SLC5A5 gene related to health conditions

Congenital hypothyroidism - caused by mutations in the SLC5A5 gene

       Several SLC5A5 gene mutations have been identified in people with congenital hypothyroidism. 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 range from mild to severe depending on the level of hormone production. In many cases, the thyroid gland is enlarged (goiter) in an attempt to compensate for reduced hormone production.

d.   The SLC5A5 gene located

       Cytogenetic Location: 19p13.2-p12. Molecular Location on chromosome 19: base pairs 17,982,781 to 18,005,982. The SLC5A5 gene is located on the short (p) arm of chromosome 19 between positions 13.2 and 12. More precisely, the SLC5A5 gene is located from base pair 17,982,781 to base pair 18,005,982 on chromosome 19.