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

Summary

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

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_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
Observational study of gene-disease association. (HuGE Navigator)
Title: The cytosolic β-glucosidase GBA3 does not influence type 1 Gaucher disease manifestation.
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.
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.

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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 EBI GWAS CatalogPubMed
Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D4S1118 (e-PCR)
- UniSTS:290

NoName (e-PCR)
- UniSTS:486950

SHGC-24823 (e-PCR)
- UniSTS:6469

RH93679 (e-PCR)
- UniSTS:89944

G33991 (e-PCR)
- UniSTS:29538

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

EC 3.2.1.21

EC 3.2.1.45

EC 3.2.1.46

NP_001264154.1

EC 3.2.1.21

EC 3.2.1.45

EC 3.2.1.46

NP_066024.1

EC 3.2.1.21

EC 3.2.1.45

EC 3.2.1.46

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)

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
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
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

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
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
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