GBA1 Gene (Glucosylceramidase Beta 1)
GBA1: A key gene in Gaucher disease, Parkinson's disease, and lysosomal function.
Gene Information Card
| Symbol | GBA1 |
|---|---|
| Full Name | Glucosylceramidase Beta 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q22 |
| NCBI Gene ID | 2629 ncbi.nlm.nih.gov/gene/2629 |
| Ensembl ID | ENSG00000177628 |
| UniProt ID | P04062 |
| OMIM ID | 606463 |
| HGNC ID | 4177 |
| Aliases | GBA, GCB, GLUC, GBA1A, GBA1B |
Description
The GBA1 gene encodes the lysosomal enzyme glucocerebrosidase (also known as beta-glucocerebrosidase). This enzyme catalyzes the hydrolysis of glucocerebroside to glucose and ceramide. Mutations in GBA1 cause Gaucher disease, the most common lysosomal storage disorder, and are a major genetic risk factor for Parkinson's disease and Lewy body dementia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gaucher disease (type 1, 2, 3) | Loss-of-function mutations in GBA1 lead to accumulation of glucocerebroside in macrophages, causing organomegaly, bone lesions, and neurological symptoms. | OMIM #230800, #230900, #231000 |
| Parkinson's disease | Heterozygous GBA1 mutations increase risk (odds ratio ~5) via lysosomal dysfunction and alpha-synuclein accumulation. | ClinVar, PMID: 19597539 |
| Lewy body dementia | GBA1 variants are associated with increased risk and earlier onset of dementia with Lewy bodies. | ClinVar, PMID: 26940714 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 45.2 | High |
| Liver | 32.1 | High |
| Lung | 18.5 | Medium |
| Brain (cerebellum) | 12.3 | Medium |
| Heart | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 35.0 | High expression |
| HepG2 | 28.4 | High expression |
| SH-SY5Y | 15.2 | Moderate expression |
| K562 | 22.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1226A>G (p.Asn409Ser) | Missense | ~70% in Ashkenazi Jewish Gaucher patients | Reduced enzyme activity; common in Gaucher type 1 |
| c.1448T>C (p.Leu483Pro) | Missense | ~30% in non-Jewish Gaucher patients | Severe enzyme deficiency; associated with neuronopathic Gaucher |
| c.84dupG | Frameshift | Rare | Null allele; causes severe Gaucher disease |
| c.1604G>A (p.Arg535His) | Missense | ~3% in Parkinson's disease cohorts | Moderate loss of function; increases Parkinson's risk |
Mutation functional classification
Loss of Function (LOF)
Most GBA1 mutations reduce or eliminate glucocerebrosidase activity, leading to substrate accumulation and lysosomal dysfunction.
Gain of Function (GOF)
Not described for GBA1; no evidence of gain-of-function mutations.
Dominant Negative (DN)
Heterozygous mutations in GBA1 are thought to act via haploinsufficiency or dominant-negative effects on lysosomal function, though the exact mechanism in Parkinson's disease is debated.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004348 - glucosylceramidase activity | • GO:0005764 - lysosome |
| • GO:0006680 - glucosylceramide catabolic process | • GO:0007040 - lysosomal protein catabolic process |
| • GO:0016787 - hydrolase activity |
Pathways
• KEGG: hsa00600 - Sphingolipid metabolism
• KEGG: hsa04142 - Lysosome
• Reactome: R-HSA-1660662 - Glycosphingolipid metabolism
Protein Summary
Glucocerebrosidase (UniProt P04062) is a 536-amino-acid lysosomal enzyme that cleaves the beta-glucosidic linkage of glucocerebroside. It requires the cofactor saposin C for optimal activity. The protein is synthesized as a precursor and processed in the lysosome. Mutations cause enzyme deficiency, leading to Gaucher disease, and heterozygosity increases Parkinson's disease risk.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GBA1 Knockout HEK293 Cell Line | EDC90036 | Human | 2629 | Details Get a Quote |
| GBA1 Knockout A-549 Cell Line | EDJ-KQ43222 | Human | 2629 | Details Get a Quote |
| GBA1 Knockout HCT 116 Cell Line | EDJ-KQ43223 | Human | 2629 | Details Get a Quote |
| GBA1 Knockout HeLa Cell Line | EDC08301 | Human | 2629 | Details Get a Quote |
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