UAP1 (UDP-N-Acetylglucosamine Pyrophosphorylase 1)
Key enzyme in hexosamine biosynthesis and protein glycosylation
Gene Information Card
| Symbol | UAP1 |
|---|---|
| Full Name | UDP-N-Acetylglucosamine Pyrophosphorylase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 6675 ncbi.nlm.nih.gov/gene/6675 |
| Ensembl ID | ENSG00000117155 |
| UniProt ID | Q16222 |
| OMIM ID | 602862 |
| HGNC ID | 12460 |
| Aliases | AGX1, SPAG2, UAP1L1 |
Description
UAP1 encodes UDP-N-acetylglucosamine pyrophosphorylase 1, a key enzyme in the hexosamine biosynthetic pathway that catalyzes the formation of UDP-N-acetylglucosamine (UDP-GlcNAc) from UTP and N-acetylglucosamine-1-phosphate. UDP-GlcNAc is a critical substrate for N- and O-linked glycosylation, GPI anchor biosynthesis, and chitin synthesis in fungi. The enzyme is essential for cellular glycosylation processes and is implicated in cancer metabolism and congenital disorders of glycosylation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation type IIn (CDG-IIn) | Deficient UAP1 activity reduces UDP-GlcNAc availability, impairing N-glycosylation | OMIM #602862; ClinVar |
| Colorectal cancer | UAP1 overexpression promotes O-GlcNAcylation and tumor growth via hexosamine pathway flux | COSMIC; PMID: 25605248 |
| Breast cancer | UAP1 upregulation correlates with poor prognosis and increased O-GlcNAc modification | COSMIC; PMID: 28431213 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 10.2 | High |
| Pancreas | 8.9 | Medium |
| Brain | 6.3 | Medium |
| Lung | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.8 | Cervical cancer cell line |
| HepG2 | 13.2 | Hepatocellular carcinoma |
| MCF7 | 11.5 | Breast cancer cell line |
| A549 | 9.7 | Lung adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of function; associated with CDG-IIn |
| c.742C>T (p.Arg248Trp) | Missense | <0.01% | Reduced enzyme activity; reported in ClinVar |
| c.1073G>A (p.Arg358Gln) | Missense | <0.01% | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous missense mutations (e.g., p.Met1?, p.Arg248Trp) reduce or abolish UAP1 enzymatic activity, leading to UDP-GlcNAc deficiency and congenital disorder of glycosylation.
Gain of Function (GOF)
Not reported; overexpression in cancers is transcriptional rather than mutational.
Dominant Negative (DN)
Not described for UAP1.
View complete mutation data：
Gene Ontology (GO)
| • UDP-N-acetylglucosamine diphosphorylase activity (GO:0003977) | • UDP-N-acetylglucosamine biosynthetic process (GO:0006047) |
| • protein glycosylation (GO:0006486) | • cytosol (GO:0005829) |
| • cytoplasm (GO:0005737) |
Pathways
• Hexosamine biosynthetic pathway (Reactome: R-HSA-446203)
• N-glycan biosynthesis (Reactome: R-HSA-446193)
• O-linked glycosylation (Reactome: R-HSA-5173105)
Protein Summary
UAP1 is a 508-amino acid cytoplasmic enzyme that catalyzes the rate-limiting step in UDP-GlcNAc production. The protein exists as a homodimer and requires Mg2+ for activity. Its structure includes a nucleotide-binding domain and a sugar-binding domain. Post-translational modifications include phosphorylation at Ser264, which modulates activity. UAP1 is ubiquitously expressed with highest levels in liver and kidney.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UAP1 Knockout HEK293 Cell Line | EDJ-KQ5829 | Human | 6675 | Details Get a Quote |
| UAP1L1 Knockout HEK293 Cell Line | EDJ-KQ10726 | Human | 91373 | Details Get a Quote |
| UAP1L1 Knockout HCT 116 Cell Line | EDJ-KQ36997 | Human | 91373 | Details Get a Quote |
| UAP1 Knockout A-549 Cell Line | EDJ-KQ29265 | Human | 6675 | Details Get a Quote |
| UAP1 Knockout HCT 116 Cell Line | EDJ-KQ29266 | Human | 6675 | Details Get a Quote |
| UAP1 Knockout HeLa Cell Line | EDJ-KQ29267 | Human | 6675 | Details Get a Quote |
| UAP1L1 Knockout A-549 Cell Line | EDJ-KQ38291 | Human | 91373 | Details Get a Quote |
| UAP1L1 Knockout HeLa Cell Line | EDJ-KQ38293 | Human | 91373 | Details Get a Quote |
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