DPAGT1: Dolichyl-Phosphate N-Acetylglucosaminephosphotransferase 1
Key enzyme in N-linked glycosylation; associated with congenital disorders of glycosylation and myasthenic syndromes
Gene Information Card
| Symbol | DPAGT1 |
|---|---|
| Full Name | Dolichyl-Phosphate N-Acetylglucosaminephosphotransferase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.3 |
| NCBI Gene ID | 1798 ncbi.nlm.nih.gov/gene/1798 |
| Ensembl ID | ENSG00000149269 |
| UniProt ID | Q9H3H5 |
| OMIM ID | 191350 |
| HGNC ID | 2995 |
| Aliases | ALG7, CDG-Ij, D11S366, DPAGT2, G1PT, GPT, UAGT |
Description
DPAGT1 encodes dolichyl-phosphate N-acetylglucosaminephosphotransferase 1, an enzyme that catalyzes the first committed step in the dolichol-linked oligosaccharide pathway for N-linked protein glycosylation. This reaction transfers N-acetylglucosamine-1-phosphate from UDP-N-acetylglucosamine to dolichyl phosphate. Mutations in DPAGT1 cause congenital disorder of glycosylation type Ij (DPAGT1-CDG) and are also associated with limb-girdle myasthenia gravis with tubular aggregates (CMS13).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation type Ij (DPAGT1-CDG) | Loss-of-function mutations impair N-glycosylation, leading to multisystem disease | OMIM #608093 |
| Myasthenic syndrome, congenital, 13 (CMS13) | Hypomorphic mutations reduce enzyme activity, affecting neuromuscular junction glycosylation | OMIM #614750 |
| Limb-girdle myasthenia gravis with tubular aggregates | DPAGT1 mutations cause defective glycosylation of acetylcholine receptor subunits | ClinVar, PMID: 22980766 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Brain | 8.7 | Medium |
| Heart | 6.5 | Low |
| Kidney | 10.1 | Medium |
| Pancreas | 7.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.4 | High expression |
| HeLa | 11.2 | Medium expression |
| HepG2 | 9.8 | Medium expression |
| K562 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.902G>A (p.Arg301His) | Missense | Rare | Reduced enzyme activity; associated with CMS13 |
| c.958C>T (p.Arg320*) | Nonsense | Rare | Loss of function; associated with DPAGT1-CDG |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of function; severe DPAGT1-CDG |
| c.1160T>C (p.Leu387Pro) | Missense | Rare | Impaired protein stability; CMS13 |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg320*) lead to truncated, non-functional protein, causing severe DPAGT1-CDG.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; DPAGT1-CDG and CMS13 are autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase activity (GO:0003975) | • protein glycosylation (GO:0006486) |
| • endoplasmic reticulum membrane (GO:0005789) | • integral component of membrane (GO:0016021) |
| • oligosaccharide-lipid intermediate biosynthetic process (GO:0006490) |
Pathways
• KEGG hsa00510 - N-Glycan biosynthesis
• Reactome R-HSA-446193 - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide
• LLO)
• Reactome R-HSA-678662 - N-glycan antennae elongation
Protein Summary
DPAGT1 is a 408-amino acid transmembrane protein localized to the endoplasmic reticulum membrane. It catalyzes the transfer of N-acetylglucosamine-1-phosphate to dolichyl phosphate, forming N-acetylglucosaminyl-dolichyl phosphate (GlcNAc-PP-dolichol). This is the first and rate-limiting step in the assembly of the lipid-linked oligosaccharide precursor required for N-linked glycosylation. The protein contains a conserved glycosyltransferase domain and multiple transmembrane helices. Defects in DPAGT1 lead to underglycosylation of proteins, affecting multiple organ systems.
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