GNPTAB gene

The GNPTAB gene is responsible for creating subunits of an enzyme that tags specific proteins for transport to lysosomes, the cell's recycling centers.

Normal Function

The GNPTAB gene provides instructions for making two parts—the alpha and beta subunits—of an enzyme called GlcNAc-1-phosphotransferase. This enzyme is composed of two alpha (α), two beta (β), and two gamma (γ) subunits (the gamma subunit is produced by the GNPTG gene). GlcNAc-1-phosphotransferase helps prepare certain newly made enzymes for transport to lysosomes, which are compartments within the cell that use digestive enzymes called hydrolases to break down large molecules for reuse.

The enzyme is involved in the first step of creating a molecule called mannose-6-phosphate (M6P). M6P acts as a tag that signals a hydrolase should be transported to the lysosome. Specifically, GlcNAc-1-phosphotransferase transfers a molecule called GlcNAc-1-phosphate to a newly produced hydrolase. In a subsequent step, a molecule is removed to reveal the M6P tag, allowing the hydrolase to be transported to the lysosome.

Health Conditions Related to Genetic Changes

Mucolipidosis II alpha/beta

Approximately 50 mutations in the GNPTAB gene have been identified as causes of mucolipidosis II alpha/beta. These mutations prevent the production of functional GlcNAc-1-phosphotransferase. Without this enzyme, hydrolases cannot be tagged with M6P and transported to lysosomes. Instead, these enzymes end up outside the cell, where they exhibit increased digestive activity. The resulting lack of hydrolases within lysosomes causes large molecules to accumulate, characterizing this as a lysosomal storage disorder.

Mucolipidosis III alpha/beta

Mutations in the GNPTAB gene can also cause mucolipidosis III alpha/beta. In these cases, mutations result in reduced activity of GlcNAc-1-phosphotransferase, which disrupts the tagging of hydrolases. Similar to mucolipidosis II, the shortage of these digestive enzymes within lysosomes leads to the accumulation of large molecules, classifying this condition as a lysosomal storage disorder.

Other Names for This Gene

• alpha-beta GlcNAc-1-phosphotransferase
• DKFZp762B226
• GlcNAc phosphotransferase
• GlcNAc-1-phosphotransferase
• GNPTA
• GNPTA_HUMAN
• KIAA1208
• MGC4170
• N-acetylglucosamine-1-phosphate transferase
• N-acetylglucosamine-1-phosphate transferase alpha and beta subunits
• UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosamine
• uridine 5'-diphosphate-N-acetylglucosamine: lysosomal hydrolase N-acetyl-1-phosphotransferase