GNPTG

GNPTG is the gene encoding the gamma subunit of N-acetylglucosamine-1-phosphotransferase, an enzyme complex that initiates the addition of mannose-6-phosphate tags to lysosomal hydrolases in the Golgi apparatus. In humans, this gamma subunit forms a heterotrimer with the alpha and beta subunits encoded by GNPTAB.

The complex catalyzes the first step of the mannose-6-phosphate tagging pathway, essential for delivery of lysosomal enzymes to lysosomes. Mutations in GNPTG reduce activity or stability of the complex, leading to partial deficiency of M6P tagging and misdirection or extracellular secretion of lysosomal hydrolases.

GNPTG mutations cause mucolipidosis type III gamma, a rare autosomal recessive lysosomal storage disorder. The phenotype ranges from mild to moderate and is typically milder than mucolipidosis II/III caused by GNPTAB mutations. Features may include skeletal abnormalities, joint stiffness, short stature, and developmental delay; some patients have distinctive facial features and organ involvement.

Diagnosis is based on genetic testing for GNPTG mutations and may be supported by biochemical studies showing reduced lysosomal enzyme targeting and abnormal distributions of lysosomal enzymes in cultured cells or plasma enzyme patterns.

Management is supportive and multidisciplinary, addressing orthopedic, developmental, and respiratory needs. There is no disease-specific cure; research continues on therapies to restore proper lysosomal enzyme targeting.