SLC5A5

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.

congenital hypothyroidism - caused by mutations in the SLC5A5 gene

Several SLC5A5 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 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.