GNPTAB: N-acetylglucosamine-1-phosphate transferase subunit alpha/beta
Key enzyme in lysosomal enzyme targeting; mutations cause mucolipidosis II and III
Gene Information Card
| Symbol | GNPTAB |
|---|---|
| Full Name | N-acetylglucosamine-1-phosphate transferase subunit alpha/beta |
| Gene Type | Protein coding |
| Chromosomal Location | 12q23.2 |
| NCBI Gene ID | 79158 ncbi.nlm.nih.gov/gene/79158 |
| Ensembl ID | ENSG00000111665 |
| UniProt ID | Q3T906 |
| OMIM ID | 607840 |
| HGNC ID | 29670 |
| Aliases | GNPTA, GNPTB, MGC4170, FLJ22171 |
Description
The GNPTAB gene encodes the alpha and beta subunits of N-acetylglucosamine-1-phosphate transferase (GlcNAc-1-phosphotransferase), a key enzyme in the mannose 6-phosphate (M6P) tagging pathway. This enzyme catalyzes the first step in the synthesis of the M6P recognition marker on lysosomal hydrolases, which is essential for their proper trafficking to lysosomes. Mutations in GNPTAB lead to deficiencies in lysosomal enzyme targeting, resulting in the accumulation of undigested substrates and causing the autosomal recessive lysosomal storage disorders mucolipidosis II (I-cell disease) and mucolipidosis III alpha/beta.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucolipidosis II (I-cell disease) | Loss-of-function mutations in GNPTAB abolish GlcNAc-1-phosphotransferase activity, preventing M6P tagging and causing misrouting of lysosomal enzymes to the extracellular space. This leads to severe lysosomal storage in multiple tissues. | ClinVar, OMIM |
| Mucolipidosis III alpha/beta | Hypomorphic mutations in GNPTAB result in residual enzyme activity, leading to a milder, later-onset form of lysosomal storage disease with progressive skeletal dysplasia and joint stiffness. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Brain | 8.7 | Medium |
| Heart | 7.1 | Low |
| Lung | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression |
| HeLa | 12.3 | Medium expression |
| HepG2 | 11.8 | Medium expression |
| K562 | 9.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3503_3504delTC | Frameshift | Common in MLII | Loss of function |
| c.2715+1G>A | Splice site | Reported in MLIII | Reduced function |
| c.1208C>T (p.Ser403Leu) | Missense | Rare | Loss of function |
| c.3565C>T (p.Arg1189*) | Nonsense | Reported in MLII | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most GNPTAB mutations result in complete or partial loss of GlcNAc-1-phosphotransferase activity, leading to mucolipidosis II or III.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GNPTAB.
Dominant Negative (DN)
No dominant-negative mutations have been described for GNPTAB.
View complete mutation data：
Gene Ontology (GO)
| • N-acetylglucosamine-1-phosphotransferase activity (GO:0003976) | • Golgi apparatus (GO:0005794) |
| • Lysosomal enzyme mannose 6-phosphate tagging (GO:0007040) | • Protein glycosylation (GO:0006486) |
Pathways
• Lysosome (KEGG: hsa04142)
• Mannose 6-phosphate receptor pathway (Reactome: R-HSA-8953897)
Protein Summary
The GNPTAB gene product is a 1256-amino acid precursor protein that is cleaved into alpha and beta subunits, which together form the catalytic core of GlcNAc-1-phosphotransferase. This enzyme resides in the Golgi apparatus and transfers N-acetylglucosamine-1-phosphate to mannose residues on lysosomal hydrolases, generating the M6P tag essential for receptor-mediated transport to lysosomes. Deficiency leads to severe lysosomal storage disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNPTAB Knockout HEK293 Cell Line | EDJ-KQ1986 | Human | 79158 | Details Get a Quote |
| GNPTAB Knockout A-549 Cell Line | EDJ-KQ21968 | Human | 79158 | Details Get a Quote |
| GNPTAB Knockout HCT 116 Cell Line | EDJ-KQ21969 | Human | 79158 | Details Get a Quote |
| GNPTAB Knockout HeLa Cell Line | EDJ-KQ21970 | Human | 79158 | Details Get a Quote |
| GNPTAB Knockout PANC-1 Cell Line | EDC90485 | Human | 79158 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
