GNPTG Gene - N-Acetylglucosamine-1-Phosphotransferase Subunit Gamma
Mucolipidosis III Gamma and Lysosomal Enzyme Targeting
Gene Information Card
| Symbol | GNPTG |
|---|---|
| Full Name | N-acetylglucosamine-1-phosphotransferase subunit gamma |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 84572 ncbi.nlm.nih.gov/gene/84572 |
| Ensembl ID | ENSG00000103174 |
| UniProt ID | Q9UMS4 |
| OMIM ID | 607838 |
| HGNC ID | 23026 |
| Aliases | GNPTAG, C16orf27, FLJ22059, LP5085 |
Description
The GNPTG gene encodes the gamma subunit of N-acetylglucosamine-1-phosphotransferase, a heteromeric enzyme that catalyzes the first step in the synthesis of mannose 6-phosphate (M6P) recognition markers on lysosomal hydrolases. This modification is critical for targeting newly synthesized lysosomal enzymes to the lysosome. Mutations in GNPTG cause mucolipidosis III gamma (ML3 gamma), a lysosomal storage disorder characterized by impaired lysosomal enzyme trafficking.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mucolipidosis III gamma | Loss-of-function mutations in GNPTG impair M6P tagging, leading to missorting of lysosomal enzymes and accumulation of undegraded substrates in lysosomes. | OMIM #252605; ClinVar; multiple case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 8.2 | Medium |
| Brain | 6.5 | Medium |
| Liver | 7.1 | Medium |
| Kidney | 9.0 | Medium |
| Lung | 5.8 | Low |
| Pancreas | 4.3 | Low |
| Spleen | 6.9 | Medium |
| Testis | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.5 | High expression in embryonic kidney cells |
| HeLa | 7.8 | Moderate expression in cervical cancer cells |
| HepG2 | 6.2 | Moderate expression in liver cancer cells |
| K562 | 4.1 | Low expression in leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.445C>T (p.Arg149*) | Nonsense | Rare | Premature stop codon; loss of function |
| c.743G>A (p.Trp248*) | Nonsense | Rare | Premature stop codon; loss of function |
| c.1070_1071delAG (p.Glu357Valfs*2) | Frameshift | Rare | Frameshift leading to truncated protein; loss of function |
| c.1162C>T (p.Arg388Trp) | Missense | Rare | Likely disrupts protein folding or activity |
Mutation functional classification
Loss of Function (LOF)
Most reported GNPTG mutations are loss-of-function (nonsense, frameshift, splice-site) leading to truncated or unstable protein, causing mucolipidosis III gamma.
Gain of Function (GOF)
No gain-of-function mutations reported for GNPTG.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mannose 6-phosphate receptor mediated lysosomal enzyme targeting (Reactome: R-HSA-9634600)
• Lysosome (KEGG: hsa04142)
Protein Summary
The GNPTG protein is the gamma subunit of N-acetylglucosamine-1-phosphotransferase, a Golgi-resident transmembrane enzyme. It forms a heterohexamer with alpha/beta subunits (encoded by GNPTAB). The gamma subunit is required for full enzymatic activity and substrate recognition. Deficiency leads to failure to generate M6P tags on lysosomal hydrolases, causing their secretion instead of lysosomal delivery.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNPTG Knockout HEK293 Cell Line | EDJ-KQ10122 | Human | 84572 | Details Get a Quote |
| GNPTG Knockout A-549 Cell Line | EDJ-KQ35983 | Human | 84572 | Details Get a Quote |
| GNPTG Knockout HCT 116 Cell Line | EDJ-KQ37218 | Human | 84572 | Details Get a Quote |
| GNPTG Knockout HeLa Cell Line | EDJ-KQ37219 | Human | 84572 | Details Get a Quote |
