Sulfate (SO4 2-) is an abundant nutrient in the blood and is essential for normal growth and development. SO4 2- is conjugated (sulfonated) to many compounds in the body, including glycosaminoglycans, steroid hormones and bile acids. Sulfonation also plays an important role in the metabolism of xenobiotics and certain drugs, such as acetaminophen. SO4 2- enters and exits cells via plasma membrane SO4 2- transporters. To date, ten human SO4 2- transporters belonging to the Solute Linked Carrier 13 (SLC13) or 26 (SLC26) gene families have been identified. Clinical interest has focused on two SLC26 SO4 2- transporters which are associated with recessive human disorders: SLC26A2 is defective in four different chondrodysplasias (MED, DTD, AO2 and ACG1B) and SLC26A3 is associated with congenital chloride diarrhea (CLD). Ongoing studies are focused on the physiological significance of the other eight SO4 2- transporters (SLC13A1, A4, and SLC26A1, A6, A7, A8, A9, A11), yet to be characterized in human diseases. Our Slc13a1 null (Nas1-/-) mouse studies, have revealed several pathophysiological features associated with this transporter: hyposulfatemia, hypersulfaturia, reduced growth, seizures, behavioural abnormalities, hypercholesterolemia, fatty liver, reduced fertility and enhanced acetaminophen-induced hepatotoxicity. These findings can be relevant to single nucleotide polymorphisms (SNPs) in human SLC13A1, which lead to changes in SO4 2- transport function. This paper summarises non-synonymous SNPs (nsSNPs) found in the sulfate transporters SLC13A1, A4, and SLC26A1, A6, A7, A8, A9, A11, with a special focus on SLC13A1, which we have identified to be responsible for maintaining blood SO4 2- concentrations.
Keywords: PAPS synthetase, SLC26A2 mutations, Non-Synonymous Polymorphisms, NaS1 mRNA, SLC26A8