UGCG (UDP-Glucose Ceramide Glucosyltransferase)
Key enzyme in glycosphingolipid biosynthesis and potential therapeutic target in Gaucher disease and cancer
Gene Information Card
| Symbol | UGCG |
|---|---|
| Full Name | UDP-glucose ceramide glucosyltransferase |
| Gene Type | protein-coding |
| Chromosomal Location | 9q31.3 |
| NCBI Gene ID | 7357 ncbi.nlm.nih.gov/gene/7357 |
| Ensembl ID | ENSG00000107175 |
| UniProt ID | Q16739 |
| OMIM ID | 602874 |
| HGNC ID | 12517 |
| Aliases | GCS, GLCT1, GLE, GSL, GCS1, UDP-GlcCer glucosyltransferase |
Description
UGCG encodes glucosylceramide synthase (GCS), the enzyme that catalyzes the first glycosylation step in glycosphingolipid biosynthesis, transferring glucose from UDP-glucose to ceramide to form glucosylceramide. This enzyme is critical for maintaining cellular glycosphingolipid homeostasis and is implicated in Gaucher disease, cancer progression, and multidrug resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gaucher disease type 1 | Loss-of-function mutations in UGCG reduce glucosylceramide synthase activity, leading to accumulation of glucosylceramide in macrophages. | ClinVar, OMIM |
| Gaucher disease type 2 | Severe deficiency of GCS due to biallelic UGCG mutations causes neuronopathic Gaucher disease. | ClinVar, OMIM |
| Gaucher disease type 3 | Partial loss-of-function UGCG variants result in chronic neuronopathic Gaucher disease. | ClinVar, OMIM |
| Cancer (various) | Overexpression of UGCG in tumors increases glucosylceramide levels, promoting drug resistance and metastasis. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain | 6.1 | Low |
| Lung | 4.7 | Low |
| Colon | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| MCF7 | 10.8 | Breast cancer cell line |
| A549 | 7.4 | Lung cancer cell line |
| K562 | 5.1 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1208G>A (p.Arg403Gln) | Missense | Rare | Reduced enzyme activity; associated with Gaucher disease |
| c.1448T>C (p.Leu483Pro) | Missense | Rare | Loss of function; Gaucher disease |
| c.680A>G (p.Asn227Ser) | Missense | Rare | Decreased GCS activity; Gaucher disease |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of function; severe Gaucher disease |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations in UGCG reduce or abolish glucosylceramide synthase activity, leading to glucosylceramide accumulation and Gaucher disease phenotypes.
Gain of Function (GOF)
Not well documented; overexpression in cancer cells is associated with increased glucosylceramide synthesis and drug resistance.
Dominant Negative (DN)
No dominant-negative UGCG mutations have been reported in the literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glycosphingolipid biosynthesis - lacto and neolacto series (KEGG: hsa00601)
• Sphingolipid metabolism (KEGG: hsa00600)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
Glucosylceramide synthase (GCS) is a 394-amino-acid transmembrane protein localized to the Golgi apparatus. It catalyzes the transfer of glucose from UDP-glucose to ceramide, producing glucosylceramide, the precursor for all glycosphingolipids. GCS is essential for cellular signaling, membrane integrity, and lipid raft formation. Its dysregulation contributes to lysosomal storage disorders and cancer chemoresistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UGCG Knockout HEK293 Cell Line | EDJ-KQ2506 | Human | 7357 | Details Get a Quote |
| UGCG Knockout A-549 Cell Line | EDJ-KQ23102 | Human | 7357 | Details Get a Quote |
| UGCG Knockout HCT 116 Cell Line | EDJ-KQ23103 | Human | 7357 | Details Get a Quote |
| UGCG Knockout HeLa Cell Line | EDJ-KQ23104 | Human | 7357 | Details Get a Quote |
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