GBA3 (Glucosylceramidase Beta 3)
Gene encoding a cytosolic beta-glucosidase involved in glycosphingolipid metabolism
Gene Information Card
| Symbol | GBA3 |
|---|---|
| Full Name | Glucosylceramidase Beta 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 4p15.2 |
| NCBI Gene ID | 57733 ncbi.nlm.nih.gov/gene/57733 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q9H227 |
| OMIM ID | 606423 |
| HGNC ID | 4178 |
| Aliases | CBG, CBGL1, GBA3, GLUC, KLRP, MGC126616, MGC126618 |
Description
GBA3 (Glucosylceramidase Beta 3) encodes a cytosolic beta-glucosidase that hydrolyzes glucosylceramide and other beta-glucosides. It is involved in glycosphingolipid metabolism and may play a role in cellular detoxification of xenobiotics. The enzyme is distinct from lysosomal GBA (glucocerebrosidase) and is expressed in various tissues, particularly liver and kidney.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gaucher disease (atypical) | Loss of GBA3 activity may contribute to substrate accumulation in non-lysosomal compartments; however, primary Gaucher disease is caused by GBA mutations. | ClinVar, OMIM |
| Parkinson disease (potential modifier) | Reduced GBA3 activity may alter glycosphingolipid homeostasis, potentially modifying risk in GBA mutation carriers. | ClinVar, PubMed |
| Cancer (colorectal, liver) | Altered GBA3 expression has been observed in tumor tissues; functional significance under investigation. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Small intestine | 6.1 | Low |
| Colon | 4.7 | Low |
| Spleen | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate expression |
| Caco-2 (colon) | 5.4 | Low expression |
| K562 (leukemia) | 2.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.857C>T (p.Thr286Met) | Missense | 0.001% (gnomAD) | Reduced enzyme activity in vitro |
| c.112G>A (p.Gly38Arg) | Missense | 0.0005% (gnomAD) | Unknown functional effect |
| c.1361_1362del (p.Gln454fs) | Frameshift | <0.001% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense variants that truncate the protein or disrupt catalytic residues are predicted to cause loss of enzymatic activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GBA3.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for GBA3.
View complete mutation data：
Gene Ontology (GO)
| • glucosylceramidase activity (GO:0004348) | • beta-glucosidase activity (GO:0008422) |
| • glucosylceramide catabolic process (GO:0006680) | • cytosol (GO:0005829) |
| • extracellular exosome (GO:0070062) |
Pathways
• Glycosphingolipid metabolism (Reactome: R-HSA-1660661)
• Sphingolipid metabolism (KEGG: hsa00600)
Protein Summary
GBA3 is a 536-amino acid cytosolic beta-glucosidase that catalyzes the hydrolysis of glucosylceramide to glucose and ceramide. It belongs to glycosyl hydrolase family 1 and is distinct from the lysosomal GBA. The protein is expressed in liver, kidney, and intestine, and may have a role in detoxifying plant glycosides and xenobiotics. Structural studies show a TIM barrel fold with a catalytic acid/base and nucleophile.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GBA3 Knockout HEK293 Cell Line | EDJ-KQ13574 | Human | 57733 | Details Get a Quote |
| GBA3 Knockout A-549 Cell Line | EDJ-KQ41966 | Human | 57733 | Details Get a Quote |
| GBA3 Knockout HCT 116 Cell Line | EDJ-KQ43226 | Human | 57733 | Details Get a Quote |
| GBA3 Knockout HeLa Cell Line | EDJ-KQ43227 | Human | 57733 | Details Get a Quote |
