NAGPA (N-Acetylglucosamine-1-Phosphodiester Alpha-N-Acetylglucosaminidase)
Gene encoding the enzyme that uncovers the mannose 6-phosphate recognition marker on lysosomal hydrolases
Gene Information Card
| Symbol | NAGPA |
|---|---|
| Full Name | N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 51172 ncbi.nlm.nih.gov/gene/51172 |
| Ensembl ID | ENSG00000103175 |
| UniProt ID | Q9UK23 |
| OMIM ID | 607985 |
| HGNC ID | 8636 |
| Aliases | UCE, UNCM, NAGPA1, phosphodiester glycosidase |
Description
The NAGPA gene encodes the enzyme N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase, which catalyzes the second step in the formation of the mannose 6-phosphate (M6P) recognition marker on lysosomal hydrolases. This marker is essential for proper targeting of lysosomal enzymes to the lysosome. Mutations in NAGPA cause mucolipidosis III gamma (MLIII gamma), a disorder characterized by impaired lysosomal enzyme trafficking and accumulation of undigested substrates.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucolipidosis III gamma (MLIII gamma) | Loss-of-function mutations in NAGPA impair the uncovering of M6P residues, leading to mis-sorting of lysosomal hydrolases and their secretion into the extracellular space. | ClinVar, OMIM #252605 |
| Mucolipidosis III alpha/beta (GNPTAB-related) | Not directly caused by NAGPA, but phenotypically similar due to shared pathway defect in M6P tagging. | OMIM #252600 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Brain | 6.8 | Low |
| Heart | 5.1 | Low |
| Lung | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression |
| HeLa | 9.5 | Moderate expression |
| K562 | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1000C>T (p.Arg334*) | Nonsense | Rare (0.0001) | Loss of function; truncation of the catalytic domain |
| c.1205G>A (p.Arg402Gln) | Missense | Rare (0.0002) | Reduced enzymatic activity; associated with MLIII gamma |
| c.1556T>C (p.Leu519Pro) | Missense | Rare | Impaired protein stability and catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in NAGPA result in loss of enzymatic activity, preventing the removal of N-acetylglucosamine from the M6P phosphodiester, thereby disrupting lysosomal enzyme targeting.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NAGPA.
Dominant Negative (DN)
No dominant-negative mutations have been described; MLIII gamma is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mannose 6-phosphate receptor mediated lysosomal enzyme targeting (Reactome: R-HSA-9634600)
• Lysosomal enzyme post-translational modification (KEGG: hsa04142)
Protein Summary
NAGPA is a 1036-amino acid type I transmembrane glycoprotein localized to the Golgi apparatus. It functions as a homotetramer and catalyzes the removal of N-acetylglucosamine from the phosphodiester intermediate on lysosomal hydrolases, exposing the M6P tag. This tag is recognized by M6P receptors in the trans-Golgi network, ensuring proper lysosomal delivery. Deficiency leads to secretion of lysosomal enzymes and the clinical phenotype of mucolipidosis III gamma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NAGPA Knockout HEK293 Cell Line | EDJ-KQ51288 | Human | 51172 | Details Get a Quote |
| NAGPA Knockout HeLa Cell Line | EDJ-KQ56242 | Human | 51172 | Details Get a Quote |
| NAGPA Knockout A-549 Cell Line | EDJ-KQ64731 | Human | 51172 | Details Get a Quote |
| NAGPA Knockout HCT 116 Cell Line | EDJ-KQ73176 | Human | 51172 | Details Get a Quote |
