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GBA3 glucosylceramidase beta 3 (gene/pseudogene) [ Homo sapiens (human) ]

Gene ID: 57733, updated on 14-Nov-2024

Summary

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Official Symbol
GBA3provided by HGNC
Official Full Name
glucosylceramidase beta 3 (gene/pseudogene)provided by HGNC
Primary source
HGNC:HGNC:19069
See related
Ensembl:ENSG00000249948 MIM:606619; AllianceGenome:HGNC:19069
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CBG; GLUC; KLRP; CBGL1
Summary
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]
Annotation information
Note: Genetic polymorphisms result in both protein coding and non-coding alleles of this gene.
Expression
Biased expression in duodenum (RPKM 80.7), small intestine (RPKM 79.2) and 3 other tissues See more
Orthologs
all
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Genomic context

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See GBA3 in Genome Data Viewer
Location:
4p15.2
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (22692937..22819569)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (22674717..22801311)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (22694560..22821192)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene adhesion G protein-coupled receptor A3 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:22524554-22525248 Neighboring gene microRNA 12115 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:22626384-22627086 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:22627087-22627788 Neighboring gene ribosomal protein S27 pseudogene 13 Neighboring gene uncharacterized LOC105374521 Neighboring gene CDC42 pseudogene 6 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:22885626-22886228 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:22944496-22945376 Neighboring gene uncharacterized LOC105374524 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:23098384-23099583 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:23236030-23237229 Neighboring gene uncharacterized LOC105374523 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21366 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21367 Neighboring gene Sharpr-MPRA regulatory region 1330 Neighboring gene ret finger protein like 4A pseudogene 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. GBA3: a polymorphic pseudogene in humans that experienced repeated gene loss during mammalian evolution. Lopes-Marques M, et al. Sci Rep, 2020 Jul 14. PMID 32665690, Free PMC Article
  2. Decreased expression of GBA3 correlates with a poor prognosis in hepatocellular carcinoma patients. Ying JF, et al. Neoplasma, 2020 Sep. PMID 32412773
  3. The crystal structure of human cytosolic beta-glucosidase unravels the substrate aglycone specificity of a family 1 glycoside hydrolase. Tribolo S, et al. J Mol Biol, 2007 Jul 27. PMID 17555766
  4. Crystal structure of the covalent intermediate of human cytosolic beta-glucosidase. Noguchi J, et al. Biochem Biophys Res Commun, 2008 Sep 26. PMID 18662675
  5. Galactosylsphingosine inhibition of the broad-specificity cytosolic beta-glucosidase of human liver. LaMarco KL, et al. Arch Biochem Biophys, 1985 Feb 1. PMID 3918500

See all (51) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. GBA3 promotes fatty acid oxidation and alleviates non-alcoholic fatty liver by increasing CPT2 transcription.
    Title: GBA3 promotes fatty acid oxidation and alleviates non-alcoholic fatty liver by increasing CPT2 transcription.
  2. Decreased expression of GBA3 correlates with a poor prognosis in hepatocellular carcinoma patients.
    Title: Decreased expression of GBA3 correlates with a poor prognosis in hepatocellular carcinoma patients.
  3. GBA3: a polymorphic pseudogene in humans that experienced repeated gene loss during mammalian evolution.
    Title: GBA3: a polymorphic pseudogene in humans that experienced repeated gene loss during mammalian evolution.
  4. cytosolic GBA3 is likely involved in the catabolism of cytosolic sialyl free N-glycans, possibly by stabilizing the activity of the NEU2 protein
    Title: 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.
  5. No correlation was observed between GBA3 1368A/T haplotypes and severity of type 1 Gaucher disease manifestation
    Title: The cytosolic β-glucosidase GBA3 does not influence type 1 Gaucher disease manifestation.
  6. Observational study of gene-disease association. (HuGE Navigator)
    Title: The cytosolic β-glucosidase GBA3 does not influence type 1 Gaucher disease manifestation.
  7. The crystal structure of a covalent intermediate of the KLrP mutant E165Q, in which glucose was covalently bound to a nucleophile, Glu(373), is reported.
    Title: Crystal structure of the covalent intermediate of human cytosolic beta-glucosidase.
  8. The positioning of a substrate molecule (quercetin-4'-glucoside) by homology modelling revealed that hydrophobic interactions dominate the binding of the aglycone moiety.
    Title: The crystal structure of human cytosolic beta-glucosidase unravels the substrate aglycone specificity of a family 1 glycoside hydrolase.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Specific alterations of the N-linked carbohydrates on HIV-1 gp120 and gp41 by glucosidases and mannosidase inhibitors can enhance mannose-binding lectin (MBL)-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL PubMed
env Glucosidase inhibitors inhibit the syncytium formation between HIV-infected and CD4-expressing cells and interfere with HIV-1 infectivity, indicating processing of HIV-1 gp120 by glucosidase is important for virus replication PubMed
env HIV-1 gp120 is extremely heavily glycosylated (31-36 N-linked glycans per molecule) by glucosidase PubMed
Envelope surface glycoprotein gp160, precursor env Oligosaccharide side-chains of HIV-1 gp160 are processed by glycosidase I and II, mannosidase I and II, acetylglucosaminyl transferase I and II, and fucosyl, galactosyl and sialyl transferases in both the endoplasmic reticulum and golgi apparatus PubMed
Envelope transmembrane glycoprotein gp41 env Mannose-containing, N-linked oligosaccharide side-chains of HIV-1 gp41 are involved in the initial stage of infection by HIV-1; glycosylation inhibitors block virus-cell and cell-cell fusion and release of the virions PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC104276, MGC126878

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables beta-galactosidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables beta-galactosidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables beta-glucosidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables galactosylceramidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables glucosylceramidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables glucosylceramidase activity TAS
Traceable Author Statement
more info
  
enables glycosylceramidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables glycosylceramidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in beta-glucoside catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in galactosylceramide catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
NOT involved_in glucosylceramide catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in glucosylceramide catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in glucosylceramide catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in glycoside catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in glycosphingolipid catabolic process TAS
Traceable Author Statement
more info
  
involved_in glycosylceramide catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in oligosaccharide catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of exo-alpha-sialidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein stabilization IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of catalytic complex IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
cytosolic beta-glucosidase
Names
cytosolic GCase
cytosolic beta-glucosidase-like protein 1
cytosolic galactosylceramidase
cytosolic glucosylceramidase
cytosolic glycosylceramidase
glucosidase beta acid 3
glucosidase, beta, acid 3 (cytosolic)
klotho-related protein
NP_001121904.1
NP_001264154.1
NP_066024.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001128432.3 → NP_001121904.1  cytosolic beta-glucosidase isoform b

    See identical proteins and their annotated locations for NP_001121904.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, coding) lacks two alternate exons resulting in the loss of an in-frame segment in the central coding region, compared to variant 1. The encoded isoform (b) has the same N- and C-termini but is shorter compared to isoform a. This variant is produced from the more frequently occurring functional allele of this gene.
    Source sequence(s)
    BC029362, CB163648
    UniProtKB/Swiss-Prot
    Q9H227
    Conserved Domains (1) summary
    cl23725
    Location:3 → 97
    Glyco_hydro_1; Glycosyl hydrolase family 1

  2. NM_001277225.2 → NP_001264154.1  cytosolic beta-glucosidase isoform c

    See identical proteins and their annotated locations for NP_001264154.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, coding) contains an alternate 5' exon and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (c) has a distinct N-terminus and is longer than isoform a. This variant is produced from the more frequently occurring functional allele of this gene.
    Source sequence(s)
    AK298377, BC029362, BC109377, CB163648
    UniProtKB/TrEMBL
    B7Z536
    Conserved Domains (1) summary
    cl23725
    Location:21 → 465
    Glyco_hydro_1; Glycosyl hydrolase family 1

  3. NM_020973.5 → NP_066024.1  cytosolic beta-glucosidase isoform a

    See identical proteins and their annotated locations for NP_066024.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1, coding) represents the longest transcript and encodes isoform a. This variant is produced from the more frequently occurring functional allele of this gene.
    Source sequence(s)
    AF323990, BC029362, BC109377, BP383134, CB163648
    UniProtKB/Swiss-Prot
    Q32LY7, Q3MIH4, Q53GG8, Q6NSF4, Q8NHT8, Q9H227, Q9H3T4, Q9H4C6
    UniProtKB/TrEMBL
    A8K9N1
    Conserved Domains (1) summary
    cl23725
    Location:3 → 464
    Glyco_hydro; Glycosyl hydrolases

RNA

  1. NR_102355.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1, non-coding) represents the longest transcript. This variant is represented as non-coding because it contains a premature stop codon compared to variant 1, and it therefore does not produce a functional protein, as indicated by experimental data in PubMed ID:20728381. This variant is produced from the non-functional reference genome allele.
    Source sequence(s)
    AF323990, BC029362, BC109377, BP383134, CB163648
    Related
    ENST00000508166.5

  2. NR_102356.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, non-coding) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because it contains a premature stop codon compared to variant 1, and it therefore does not produce a functional protein, as indicated by experimental data in PubMed ID:20728381. This variant is produced from the non-functional reference genome allele.
    Source sequence(s)
    BC029362, CB163648
    Related
    ENST00000503442.1

  3. NR_102357.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, non-coding) contains an alternate 5' exon, compared to variant 1. This variant is represented as non-coding because it contains a premature stop codon compared to variant 1, and it therefore does not produce a functional protein, as indicated by experimental data in PubMed ID:20728381. This variant is produced from the non-functional reference genome allele.
    Source sequence(s)
    AK298377, BC029362, BC109377, CB163648
    Related
    ENST00000511446.2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    22692937..22819569
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_025791774.1 Reference GRCh38.p14 PATCHES

    Range
    14730..141362
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    22674717..22801311
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9H227.2 GenPept UniProtKB/Swiss-Prot:Q9H227

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Miscellaneous