NAGLU Gene: Alpha-N-Acetylglucosaminidase | Function, Mutations & Diseases

The NAGLU gene encodes alpha-N-acetylglucosaminidase, a lysosomal enzyme that catalyzes the hydrolysis of terminal N-acetyl-D-glucosamine residues in heparan sulfate and heparin. This enzyme is essential for the stepwise degradation of glycosaminoglycans. Mutations in NAGLU lead to mucopolysaccharidosis type IIIB (Sanfilippo syndrome B), a rare autosomal recessive lysosomal storage disorder characterized by progressive neurodegeneration. The gene spans approximately 8.5 kb and contains 6 exons. The protein is synthesized as a precursor and processed to a mature form in lysosomes. NAGLU is widely expressed, with highest levels in liver, kidney, and spleen. Deficiency of the enzyme results in accumulation of heparan sulfate, leading to cellular dysfunction and clinical symptoms.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Heparan sulfate degradation (lysosomal)

• Glycosaminoglycan metabolism

• Lysosomal degradation pathway

Alpha-N-acetylglucosaminidase is a 720-amino acid glycoprotein with a molecular weight of ~82 kDa (precursor) and ~77 kDa (mature). It belongs to glycosyl hydrolase family 89. The enzyme is targeted to lysosomes via mannose-6-phosphate receptor. It cleaves terminal N-acetylglucosamine residues from heparan sulfate. The protein has a signal peptide (aa 1-23) and a propeptide that is cleaved to yield the mature enzyme. Structural studies indicate a (β/α)8 barrel domain. Mutations affecting catalytic residues or protein stability lead to disease.