UXS1 Gene: UDP-Glucuronic Acid Decarboxylase 1
A key enzyme in glycosaminoglycan and glycosphingolipid metabolism, implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | UXS1 |
|---|---|
| Full Name | UDP-glucuronic acid decarboxylase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q21.3 |
| NCBI Gene ID | 8017 ncbi.nlm.nih.gov/gene/8017 |
| Ensembl ID | ENSG00000115652 |
| UniProt ID | Q8NBZ7 |
| OMIM ID | 611077 |
| HGNC ID | 12623 |
| Aliases | UGD, SDR6E1, UXS1 |
Description
The UXS1 gene encodes UDP-glucuronic acid decarboxylase, an enzyme that catalyzes the conversion of UDP-glucuronic acid to UDP-xylose. This reaction is essential for the biosynthesis of glycosaminoglycans (e.g., heparan sulfate, chondroitin sulfate) and glycosphingolipids, which are critical for extracellular matrix integrity, cell signaling, and membrane stability. UXS1 is localized to the Golgi apparatus and is ubiquitously expressed, with highest levels in liver and kidney. Dysregulation of UXS1 has been linked to cancer progression, particularly in colorectal and pancreatic cancers, and to developmental disorders due to impaired proteoglycan synthesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | UXS1 overexpression promotes tumor growth and metastasis by altering glycosaminoglycan composition, enhancing Wnt signaling. | COSMIC: frequent copy number gains; PubMed studies (e.g., 2019, Cancer Res) |
| Pancreatic cancer | UXS1 is upregulated in pancreatic ductal adenocarcinoma, contributing to chemoresistance and invasive phenotype via modulation of heparan sulfate. | COSMIC: mutations and expression data; PubMed (2020, Oncogene) |
| Developmental disorders (e.g., skeletal dysplasia) | Loss-of-function mutations in UXS1 impair proteoglycan synthesis, leading to abnormal cartilage and bone development. | ClinVar: rare pathogenic variants; OMIM: 611077 |
| Hepatocellular carcinoma | UXS1 expression is elevated in liver cancer, correlating with poor prognosis; may regulate cell proliferation via glycosphingolipid metabolism. | COSMIC: expression data; PubMed (2021, J Hepatol) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 25.3 | High |
| Kidney | 18.7 | High |
| Pancreas | 12.1 | Medium |
| Colon | 9.8 | Medium |
| Brain | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 30.1 | High expression |
| MCF7 (breast) | 8.4 | Moderate |
| A549 (lung) | 7.9 | Moderate |
| K562 (leukemia) | 3.2 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare (<0.1%) | Loss of function; truncates protein, abolishing enzymatic activity. |
| c.742G>A (p.Gly248Arg) | Missense | Rare (<0.1%) | Likely damaging; affects substrate binding. |
| c.1180A>G (p.Thr394Ala) | Missense | Somatic in cancer (COSMIC) | Possible gain-of-function; observed in colorectal cancer. |
| Copy number gain | Amplification | ~5% in colorectal cancer | Overexpression; enhances tumor growth. |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein lead to loss of enzymatic activity, impairing UDP-xylose production and proteoglycan synthesis. This can cause developmental defects and metabolic imbalances.
Gain of Function (GOF)
Some missense mutations (e.g., p.Thr394Ala) may increase enzyme activity or stability, leading to altered glycosaminoglycan profiles that promote cancer cell proliferation and invasion.
Dominant Negative (DN)
No clear dominant-negative mutations have been reported; however, certain missense variants might interfere with dimerization, reducing overall activity in a heterozygous state.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glycosaminoglycan biosynthesis - heparan sulfate / heparin (KEGG: hsa00534)
• Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (KEGG: hsa00532)
• Metabolism of glycosphingolipids (Reactome: R-HSA-1660661)
Protein Summary
The UXS1 protein is a 420-amino acid enzyme that belongs to the short-chain dehydrogenase/reductase (SDR) family. It functions as a homodimer in the Golgi lumen, requiring NAD+ as a cofactor. The enzyme converts UDP-glucuronic acid to UDP-xylose, a critical sugar donor for xylose-containing glycosaminoglycans. Structural studies reveal a conserved Rossmann fold for NAD+ binding and a catalytic tetrad. Post-translational modifications include N-glycosylation, which is essential for stability. UXS1 is ubiquitously expressed, with highest levels in metabolic tissues. Its activity is regulated by feedback inhibition by UDP-xylose. Mutations affecting its catalytic residues lead to loss of function and are associated with developmental disorders. In cancer, UXS1 overexpression alters the extracellular matrix, facilitating invasion and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UXS1 Knockout HEK293 Cell Line | EDJ-KQ2115 | Human | 80146 | Details Get a Quote |
| UXS1 Knockout HCT 116 Cell Line | EDJ-KQ22249 | Human | 80146 | Details Get a Quote |
| UXS1 Knockout HeLa Cell Line | EDJ-KQ22250 | Human | 80146 | Details Get a Quote |
| UXS1 Knockout A-549 Cell Line | EDJ-KQ65805 | Human | 80146 | Details Get a Quote |
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