| Name | glucosidase, beta, acid 3 (gene/pseudogene) |
| Description | The protein encoded by this gene is a cytosolic enzyme that can hydrolyze several types of glycosides. The enzyme has its highest activity at neutral pH and is predominantly expressed in human liver, kidney, intestine, and spleen. This gene is a polymorphic pseudogene, with the most common allele being the functional allele that encodes the full-length protein. Some individuals contain a single nucleotide polymorphism that results in a premature stop codon in the coding region, and therefore this allele is pseudogenic due to the failure to produce a functional full-length protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2022] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGBA3, also known as cytosolic β‑glucosidase or klotho‑related protein, has been implicated in the metabolism of xenobiotic glycosides. Early studies showed that recombinant GBA3 efficiently hydrolyzed artificial substrates—such as 4‑methylumbelliferyl‑β‑D‑glucoside and synthetic glucosylceramides—while displaying minimal activity toward naturally occurring lipids like glucosylceramide and glucosylsphingosine. This enzymatic profile suggests that, despite its in vitro activity, GBA3 does not significantly modify the clinical manifestation of Gaucher disease, even in the context of known mutations that truncate and inactivate the enzyme."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and mechanistic analyses reveal that GBA3 adopts the characteristic (β/α)₈ barrel fold common to family 1 glycoside hydrolases. Crystallographic studies have pinpointed two key catalytic glutamate residues—one acting as the acid/base (Glu165) and the other as the nucleophile (Glu373)—which together facilitate a double displacement reaction mechanism. Moreover, variations in the surface loops surrounding the active site appear to be crucial for determining the enzyme’s substrate specificity, particularly toward diverse flavonoid glucosides. These detailed structural insights highlight the enzyme’s potential to interact with a range of glycosidic substrates."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its catalytic mechanism, emerging evidence points to a broader physiological role for GBA3. In human cell models, GBA3 physically associates with cytosolic sialidase NEU2, a partnership that enhances NEU2 stability and appears to promote the degradation of sialylated free N‑glycans, thereby contributing to cellular glycan catabolism. Clinically, diminished GBA3 expression has been linked to more aggressive hepatocellular carcinoma, marking it as a potential prognostic indicator and therapeutic target. In parallel, genetic analyses have revealed the accumulation of loss‑of‑function alleles, with population differences that likely reflect dietary adaptations to plant β‑glycosides. Interestingly, despite these evolutionary variations, GBA3 status does not correlate with Gaucher disease severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nick Dekker, Tineke Voorn-Brouwer, Marri Verhoek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cytosolic β-glucosidase GBA3 does not influence type 1 Gaucher disease manifestation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Cells Mol Dis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcmd.2010.07.009"}], "href": "https://doi.org/10.1016/j.bcmd.2010.07.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20728381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20728381"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sandra Tribolo, Jean-Guy Berrin, Paul A Kroon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The crystal structure of human cytosolic beta-glucosidase unravels the substrate aglycone specificity of a family 1 glycoside hydrolase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2007.05.034"}], "href": "https://doi.org/10.1016/j.jmb.2007.05.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17555766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17555766"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Junji Noguchi, Yasuhiro Hayashi, Yuichi Baba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the covalent intermediate of human cytosolic beta-glucosidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.07.089"}], "href": "https://doi.org/10.1016/j.bbrc.2008.07.089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18662675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18662675"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Li Wang, Junichi Seino, Haruna Tomotake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Co-Expression of NEU2 and GBA3 Causes a Drastic Reduction in Cytosolic Sialyl Free N-glycans in Human MKN45 Stomach Cancer Cells-Evidence for the Physical Interaction of NEU2 and GBA3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom5031499"}], "href": "https://doi.org/10.3390/biom5031499"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26193330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26193330"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "J F Ying, Y N Zhang, S S Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of GBA3 correlates with a poor prognosis in hepatocellular carcinoma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2020_190928N980"}], "href": "https://doi.org/10.4149/neo_2020_190928N980"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32412773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32412773"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Monica Lopes-Marques, Catarina Serrano, Ana R Cardoso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GBA3: a polymorphic pseudogene in humans that experienced repeated gene loss during mammalian evolution."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-68106-y"}], "href": "https://doi.org/10.1038/s41598-020-68106-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32665690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32665690"}]}]}]}
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| Synonyms | KLRP, CBGL1 |
| Proteins | GBA3_HUMAN |
| NCBI Gene ID | 57733 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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GBA3 has 2,165 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 71 datasets.
Click the + buttons to view associations for GBA3 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of GBA3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of GBA3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of GBA3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of GBA3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of GBA3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of GBA3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of GBA3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of GBA3 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of GBA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of GBA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of GBA3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of GBA3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with GBA3 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with GBA3 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with GBA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with GBA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at GBA3 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of GBA3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of GBA3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with GBA3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of GBA3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with GBA3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing GBA3 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of GBA3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of GBA3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of GBA3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of GBA3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of GBA3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of GBA3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving GBA3 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving GBA3 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving GBA3 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing GBA3 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by GBA3 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by GBA3 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by GBA3 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of GBA3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of GBA3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of GBA3 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GWASdb SNP-Disease Associations | diseases associated with GBA3 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with GBA3 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of GBA3 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HMDB Metabolites of Enzymes | interacting metabolites for GBA3 protein from the curated HMDB Metabolites of Enzymes dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with GBA3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for GBA3 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of GBA3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways | pathways involving GBA3 protein from the KEGG Pathways dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of GBA3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of GBA3 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of GBA3 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of GBA3 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
| LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of GBA3 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing GBA3 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain GBA3 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of GBA3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of GBA3 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| MW Enzyme Metabolite Associations | interacting metabolites for GBA3 protein from the MW Gene Metabolite Associations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for GBA3 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of GBA3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving GBA3 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving GBA3 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2014 | pathways involving GBA3 protein from the Reactome Pathways dataset. | |
| Reactome Pathways 2024 | pathways involving GBA3 protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of GBA3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at GBA3 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of GBA3 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of GBA3 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of GBA3 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of GBA3 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of GBA3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of GBA3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
