CFTR Modifier SLC26A9

About CFTR Modifier SLC26A9

SLC26A9 on chromosome 1q32.1 encodes a member of the SLC26 family of anion transporters, which move chloride, bicarbonate, and other anions across epithelial membranes. SLC26A9 is expressed in the airways, stomach, and pancreas, where it can act as a chloride channel or anion exchanger and contributes to fluid and bicarbonate secretion. It interacts physically and functionally with CFTR. In cystic fibrosis, genome wide association studies identified common SLC26A9 variants as modifiers of disease features, particularly the risk of meconium ileus in newborns and of cystic fibrosis related diabetes, which develops when the endocrine pancreas is damaged. Variants at this locus have also been linked to the degree of response to some CFTR modulator therapies. Modifier genes such as SLC26A9, TGFB1, and others help explain why people with identical CFTR genotypes can have markedly different disease severity. In mice, loss of Slc26a9 impairs gastric acid secretion and causes changes in airway mucus. Because SLC26A9 can provide an alternative chloride pathway, increasing its activity has been explored as a strategy that could help independently of the specific CFTR variant.