SLC9A6

The SLC9A6 gene provides instructions for making a protein called sodium/hydrogen exchanger 6 (Na+/H+ exchanger 6 or NHE6). Na+/H+ exchangers are found in the membranes that surround cells or compartments within cells. These proteins act as channels that allow positively charged sodium atoms (Na+ ions) into the cell or cellular compartment in exchange for positively charged hydrogen ions (H+, also known as protons), which are removed. The exchange of hydrogen ions helps regulate the relative acidity (pH) of the cell or cellular compartment.

The NHE6 protein is found in the membrane of compartments within the cell known as endosomes, which recycle proteins and other cellular materials. The NHE6 protein controls the pH inside endosomes, which is important for the recycling function of these compartments. The NHE6 protein may have additional functions, such as helping to move proteins to the correct location in the cell (protein trafficking).

Christianson syndrome - caused by mutations in the SLC9A6 gene

Mutations in the SLC9A6 gene lead to Christianson syndrome. This condition is characterized by neurological problems, including intellectual disabilities, seizures, and an inability to walk or speak. Mutations in the SLC9A6 gene typically lead to an abnormally short NHE6 protein that is nonfunctional or that is broken down quickly in cells, resulting in the absence of functional NHE6 channels. As a result, the pH in endosomes is not properly maintained. It is unclear how unregulated endosomal pH leads to neurological problems in people with Christianson syndrome. Some studies have shown that protein trafficking by endosomes is important for learning and memory, but the role of endosomal pH or the NHE6 protein in this process has not been identified.