N-acetylglucosamine-6-sulfatase (GNS)

N-acetylglucosamine-6-sulfatase (GNS) is a lysosomal enzyme encoded by the GNS gene on chromosome 12. It hydrolyzes sulfate groups from terminal N-acetylglucosamine residues in heparan sulfate and keratan sulfate, facilitating their degradation and recycling. Deficiency of GNS activity leads to accumulation of heparan sulfate, resulting in the lysosomal storage disorder mucopolysaccharidosis type IIID (Sanfilippo syndrome D), which primarily affects the central nervous system, causing progressive neurodegeneration, cognitive decline, behavioral disturbance, and premature death. Recombinant enzyme replacement therapy with rhGNS is under preclinical investigation, showing promise for CNS pathology correction though delivery remains a challenge.

Other names

Glucosamine-6-sulfataseN-acetylglucosamine-6-sulfatase precursorGlucosamine (N-acetyl)-6-sulfataseG6SGNS_HUMANMGC212742-acetamido-2-deoxy-D-glucose 6-sulfate sulfataseN-acetylglucosamine 6-sulfate sulfataseO,N-disulfate O-sulfohydrolaseAcetylglucosamine 6-sulfataseChondroitinsulfatase

Enzyme replacement: rhGNS restores GNS enzyme activity, reducing tissue accumulation of heparan sulfate, and correcting downstream cellular pathology including neuroinflammation