GBA2 glucosylceramidase beta 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GBA2provided by HGNC
Official Full Name: glucosylceramidase beta 2provided by HGNC
Primary source: HGNC:HGNC:18986
See related: Ensembl:ENSG00000070610 MIM:609471; AllianceGenome:HGNC:18986
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: AD035; SPG46; NLGase
Summary: This gene encodes a microsomal beta-glucosidase that catalyzes the hydrolysis of bile acid 3-O-glucosides as endogenous compounds. Studies to determine subcellular localization of this protein in the liver indicated that the enzyme was mainly enriched in the microsomal fraction where it appeared to be confined to the endoplasmic reticulum. This putative transmembrane protein is thought to play a role in carbohydrate transport and metabolism. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in small intestine (RPKM 30.3), duodenum (RPKM 27.9) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 9p13.3

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (35736866..35749228, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (35757546..35769909, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (35736863..35749225, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dystonia as initial presentation of compound heterozygous GBA2 mutations: Expanding the phenotypic spectrum of SPG46.
Title: Dystonia as initial presentation of compound heterozygous GBA2 mutations: Expanding the phenotypic spectrum of SPG46.
Truncated mutants of beta-glucosidase 2 (GBA2) are localized in the mitochondrial matrix and cause mitochondrial fragmentation.
Title: Truncated mutants of beta-glucosidase 2 (GBA2) are localized in the mitochondrial matrix and cause mitochondrial fragmentation.
results shed light on the molecular mechanism underlying the pathogenesis of GBA2-related hereditary spastic paraplegia (HSP), autosomal-recessive cerebellar ataxia (ARCA) and reveal species-specific differences in GBA2 function in vivo
Title: Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations.
We conclude that the c.1780G>C mutation results in NLGase loss of function with abolishment of the enzymatic activity and accumulation of GlcCer accompanied by a compensatory increase in GCase.
Title: Biochemical Characterization of the GBA2 c.1780G>C Missense Mutation in Lymphoblastoid Cells from Patients with Spastic Ataxia.
Demonstrate that GBA2 plays a role in the proinflammatory state characterizing cystic fibrosis cells. Report for the first time that Pseudomonas aeruginosa infection causes a recruitment of plasma membrane-associated glycosphingolipid hydrolases into lipid rafts of CuFi-1-infected cells.
Title: Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial Epithelial Cells.
Our protocol showed high specificity and sensitivity for homozygosity detection and facilitated the identification of novel mutations in GAN, GBA2, and ZFYVE26 in four families affected by hereditary spastic paraplegia or Charcot-Marie-Tooth disease
Title: Novel mutations in genes causing hereditary spastic paraplegia and Charcot-Marie-Tooth neuropathy identified by an optimized protocol for homozygosity mapping based on whole-exome sequencing.
GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology.
Title: Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden.
GBA2 mutations causing a Marinesco-Sjogren-like syndrome in two Norwegian families, are reported.
Title: GBA2 Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies.
Mutagenic analysis of TxGH116 and structural modeling of GBA2 provide a detailed structural and functional rationale for pathogenic missense mutations of GBA2
Title: Bacterial β-Glucosidase Reveals the Structural and Functional Basis of Genetic Defects in Human Glucocerebrosidase 2 (GBA2).
sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity.
Title: Identification of a feedback loop involving β-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Phenotypes

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hereditary spastic paraplegia 46 MedGen: C2828721 OMIM: 614409 GeneReviews: Not available	Compare labs

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

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

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

WI-20292 (e-PCR)
- UniSTS:36687

RH11800 (e-PCR)
- UniSTS:80517

MARC_14565-14566:1009474916:1 (e-PCR)
- UniSTS:267705

WI-19282 (e-PCR)
- UniSTS:8931

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables beta-glucosidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables beta-glucosidase activity	IDA Inferred from Direct Assay more info	PubMed
enables galactosylceramidase activity	IEA Inferred from Electronic Annotation more info
enables glucosylceramidase activity	IDA Inferred from Direct Assay more info	PubMed
enables glucosylceramidase activity	TAS Traceable Author Statement more info
enables glucosyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables steryl-beta-glucosidase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in bile acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in bile acid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in carbohydrate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in central nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in central nervous system neuron development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in cholesterol metabolic process	ISS Inferred from Sequence or Structural Similarity more info
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 glycoside catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in glycosphingolipid catabolic process	TAS Traceable Author Statement more info
involved_in lipid glycosylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of actin filament polymerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of membrane lipid distribution	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of microtubule polymerization	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in Golgi membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in smooth endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: non-lysosomal glucosylceramidase

Names: beta-glucocerebrosidase 2; bile acid beta-glucosidase GBA2; bile acid glucosyl transferase GBA2; cholesterol glucosyltransferase GBA2; cholesteryl-beta-glucosidase GBA2; glucocerebrosidase 2; glucosidase, beta (bile acid) 2; glucosylceramidase 2; non-lysosomal cholesterol glycosyltransferase; non-lysosomal galactosylceramidase; non-lysosomal glycosylceramidase

NP_001317589.1

EC 3.2.1.45

EC 3.2.1.46

NP_065995.1

EC 3.2.1.45

EC 3.2.1.46

XP_005251583.1

EC 3.2.1.45

EC 3.2.1.46

XP_006716872.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870426.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870427.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870428.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870429.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870430.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870431.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870432.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870433.1

EC 3.2.1.45

EC 3.2.1.46

XP_016870434.1

EC 3.2.1.45

EC 3.2.1.46

XP_047279568.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219312.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219313.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219314.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219315.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219316.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219317.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219318.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219319.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219320.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219321.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219322.1

EC 3.2.1.45

EC 3.2.1.46

XP_054219323.1

EC 3.2.1.45

EC 3.2.1.46

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.

Genomic

NG_033899.1 RefSeqGene

Range

5001..17363

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001330660.2 → NP_001317589.1 non-lysosomal glucosylceramidase isoform 2

Status: REVIEWED

Source sequence(s)

AB046825, AL133410, BC011363

Consensus CDS

CCDS83363.1

UniProtKB/TrEMBL

B7Z3J6

Related

ENSP00000367334.4, ENST00000378094.4
NM_020944.3 → NP_065995.1 non-lysosomal glucosylceramidase isoform 1

See identical proteins and their annotated locations for NP_065995.1

Status: REVIEWED

Source sequence(s)

AJ309567

Consensus CDS

CCDS6589.1

UniProtKB/Swiss-Prot

D3DRP2, Q5TCV6, Q96A51, Q96LY1, Q96SJ2, Q9H2L8, Q9HCG7

UniProtKB/TrEMBL

B7Z3J6

Related

ENSP00000367343.3, ENST00000378103.7

Conserved Domains (2) summary

pfam04685
Location:521 → 884

DUF608; Glycosyl-hydrolase family 116, catalytic region

pfam12215
Location:166 → 455

Glyco_hydr_116N; beta-glucosidase 2, glycosyl-hydrolase family 116 N-term

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

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

35736866..35749228 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017014940.3 → XP_016870429.1 non-lysosomal glucosylceramidase isoform X6

UniProtKB/TrEMBL

B7Z3J6
XM_017014941.3 → XP_016870430.1 non-lysosomal glucosylceramidase isoform X7

UniProtKB/TrEMBL

B7Z3J6
XM_017014937.3 → XP_016870426.1 non-lysosomal glucosylceramidase isoform X3

UniProtKB/TrEMBL

B7Z3J6
XM_017014939.3 → XP_016870428.1 non-lysosomal glucosylceramidase isoform X5

UniProtKB/TrEMBL

B7Z3J6
XM_005251526.6 → XP_005251583.1 non-lysosomal glucosylceramidase isoform X2

UniProtKB/TrEMBL

B7Z3J6

Conserved Domains (2) summary

pfam04685
Location:527 → 868

DUF608; Protein of unknown function, DUF608

pfam12215
Location:166 → 461

GBA2_N; beta-Glucocerebrosidase 2 N terminal
XM_006716809.5 → XP_006716872.1 non-lysosomal glucosylceramidase isoform X1

UniProtKB/TrEMBL

B7Z3J6

Conserved Domains (3) summary

pfam04685
Location:527 → 890

DUF608; Protein of unknown function, DUF608

pfam06202
Location:625 → 753

GDE_C; Amylo-alpha-1,6-glucosidase

pfam12215
Location:166 → 461

GBA2_N; beta-Glucocerebrosidase 2 N terminal
XM_017014938.3 → XP_016870427.1 non-lysosomal glucosylceramidase isoform X4

UniProtKB/TrEMBL

B7Z3J6
XM_017014943.3 → XP_016870432.1 non-lysosomal glucosylceramidase isoform X9

UniProtKB/TrEMBL

B4DMF0
XM_017014942.3 → XP_016870431.1 non-lysosomal glucosylceramidase isoform X8

UniProtKB/TrEMBL

B4DMF0
XM_047423612.1 → XP_047279568.1 non-lysosomal glucosylceramidase isoform X11
XM_017014945.1 → XP_016870434.1 non-lysosomal glucosylceramidase isoform X11

UniProtKB/TrEMBL

B4DMF0
XM_017014944.1 → XP_016870433.1 non-lysosomal glucosylceramidase isoform X10

UniProtKB/TrEMBL

B4DMF0