GBA2
Glucosylceramidase Beta 2
Gene Information Card
| Symbol | GBA2 |
|---|---|
| Full Name | Glucosylceramidase Beta 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 57704 ncbi.nlm.nih.gov/gene/57704 |
| Ensembl ID | ENSG00000107175 |
| UniProt ID | Q9HCG7 |
| OMIM ID | 609471 |
| HGNC ID | 18986 |
| Aliases | bile acid beta-glucosidase, glucocerebrosidase 2, NLGase |
Description
GBA2 encodes a glucosylceramidase that hydrolyzes glucosylceramide to glucose and ceramide. It is a non-lysosomal beta-glucosidase with optimal activity at neutral pH, distinct from the lysosomal GBA1. The enzyme also acts on bile acid 3-O-glucosides. Mutations in GBA2 are associated with autosomal recessive hereditary spastic paraplegia type 46 (SPG46) and cerebellar ataxia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia 46 (SPG46) | Loss-of-function mutations impair glucosylceramide hydrolysis, leading to accumulation and neuronal dysfunction. | OMIM #614409; ClinVar |
| Cerebellar ataxia, autosomal recessive | Biallelic GBA2 variants disrupt cerebellar Purkinje cell function via glucosylceramide accumulation. | OMIM #614409; PubMed studies |
| GBA2-related intellectual disability | Missense and truncating mutations reduce enzymatic activity, affecting brain development. | ClinVar; literature reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Testis | 6.1 | Low |
| Kidney | 5.4 | Low |
| Heart | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.2 | Neuronal cell line, high expression |
| HepG2 | 7.8 | Hepatocellular carcinoma, moderate expression |
| HeLa | 5.1 | Cervical carcinoma, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1780G>A (p.Asp594Asn) | Missense | Rare | Reduced enzymatic activity; associated with SPG46 |
| c.907C>T (p.Arg303*) | Nonsense | Rare | Premature stop; loss of function; SPG46 |
| c.1267C>T (p.Arg423Trp) | Missense | Rare | Impaired glucosylceramide hydrolysis; cerebellar ataxia |
Mutation functional classification
Loss of Function (LOF)
Most reported GBA2 mutations are loss-of-function, leading to reduced or absent glucosylceramidase activity, causing substrate accumulation.
Gain of Function (GOF)
No gain-of-function mutations have been documented for GBA2.
Dominant Negative (DN)
No dominant-negative effects have been reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • glucosylceramidase activity | • beta-glucosidase activity |
| • ceramide metabolic process | • sphingolipid metabolic process |
| • membrane |
Pathways
• Sphingolipid metabolism (Reactome R-HSA-428157)
• Glucosylceramide degradation (KEGG hsa00600)
Protein Summary
GBA2 is a 927-amino acid integral membrane protein localized to the endoplasmic reticulum and Golgi. It catalyzes the hydrolysis of glucosylceramide to ceramide and glucose, playing a key role in sphingolipid homeostasis. Unlike GBA1, it is not inhibited by conduritol B epoxide and has a neutral pH optimum. The protein contains a conserved glycosyl hydrolase domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GBA2 Knockout HEK293 Cell Line | EDJ-KQ12100 | Human | 57704 | Details Get a Quote |
| GBA2 Knockout HCT 116 Cell Line | EDJ-KQ39520 | Human | 57704 | Details Get a Quote |
| GBA2 Knockout A-549 Cell Line | EDJ-KQ40775 | Human | 57704 | Details Get a Quote |
| GBA2 Knockout HeLa Cell Line | EDJ-KQ40776 | Human | 57704 | Details Get a Quote |
