GBA1

Chr 1

glucosylceramidase beta 1

Also known as: GBA, GCB, GLUC

NCBI Gene: 2629 ENSG00000177628 UniProt: P04062

This gene encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide during glycolipid metabolism. Mutations cause Gaucher disease types I, II, III, and IIIC through autosomal recessive inheritance, resulting in accumulation of glucocerebrosides due to deficient enzyme activity. The gene also confers susceptibility to late-onset Parkinson disease and Lewy body dementia through multifactorial and autosomal dominant mechanisms.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism. Mutations in this gene cause Gaucher disease, a lysosomal storage disease characterized by an accumulation of glucocerebrosides. A related pseudogene is approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGaucher disease

UniProtGaucher disease 1

UniProtGaucher disease 2

UniProtGaucher disease 3

Clinical highlights

Gene-disease validity (ClinGen)

Parkinson disease · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

318

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — GBA1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.36

OE 0.51 (0.34–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.17Z-score

OE missense 0.81 (0.73–0.90)

248 obs / 305.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.34–0.80)

0≤0.351.4

Missense OE?0.81 (0.73–0.90)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 14 / 27.3Missense obs/exp: 248 / 305.8Syn Z: -0.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GBA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — GBA1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Gaucher Disease, Type 1Healthy

Prodromal Parkinsonian Features in GBA1 Mutation Carriers

RECRUITING

NCT05253560Shaare Zedek Medical CenterStarted 2017-05-16

The investigators aim to identify prodromal PD in a cohort of carriers of Gaucher disease.

Parkinson's Disease

Genotypic Influences on Network Progression in Parkinson's Disease

ACTIVE NOT RECRUITING

NCT04228172Northwell HealthStarted 2020-02-24

DNA/GeneticTestingFDG PET scanMRI scan

Parkinson Disease

Chinese PD-GBA Registry

RECRUITING

NCT03523065Xiangya Hospital of Central South UniversityStarted 2017-02-01

Parkinson DiseaseNervous System DisorderNeurodegenerative Diseases

Molecular and Functional Imaging in Monogenic PD.

RECRUITING

NCT05518617University of ExeterStarted 2022-07-01

Positron Emission Tomography (PET) scan using DASB tracer

Parkinson Disease

Phase 1/2a Clinical Trial of PR001 (LY3884961) in Patients With Parkinson's Disease With at Least One GBA1 Mutation (PROPEL)

ACTIVE NOT RECRUITING

NCT04127578Phase PHASE1, PHASE2Prevail TherapeuticsStarted 2020-01-03

LY3884961MethylprednisoloneSirolimus

Parkinson's Disease (PD)GBA1 Parkinson DiseaseREM Sleep Behavior Disorder (iRBD)

Understanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging

NOT YET RECRUITING

NCT07474779Phase NAUniversity of PaviaStarted 2026-05-11

brain imagingblood drawSkin biopsy

Parkinson's Disease

Prevent Cognitive Decline in GBA-associated Parkinson's Disease

NOT YET RECRUITING

NCT07055087Phase PHASE2University Hospital TuebingenStarted 2025-12

PrasinezumabSodium Chloride

Type II Gaucher Disease

An Exploratory Clinical Trial of VGN-R08b in Patients With Type II Gaucher Disease

RECRUITING

NCT06272149Phase EARLY_PHASE1Xinhua Hospital, Shanghai Jiao Tong University School of MedicineStarted 2023-03-01

VGN-R08b

Gaucher Disease

Screening for Gaucher Disease and Acid Sphingomyelinase Deficiency

NOT YET RECRUITING

NCT06258577Chung-Hsing WangStarted 2024-05-01

Parkinson's Disease (PD)

A Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Intracerebral Injection of LY-N001 Injection for the Treatment of Moderate to Advanced Parkinson's Disease With GBA1 Mutations

NOT YET RECRUITING

NCT07685444Phase EARLY_PHASE1Lingyi Biotech Co., Ltd.Started 2026-07-07

LY-N001 Injection

Parkinson Disease

Effectiveness of Cognitive Stimulation Treatment in Patients With Parkinson's Disease

RECRUITING

NCT06323278Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2021-12-21

Cognitive training

Gaucher DiseaseParkinson DiseaseGBA Gene Mutation

World Data on Ambroxol for Patients With GD and GBA Related PD

RECRUITING

NCT04388969Shaare Zedek Medical CenterStarted 2020-05-06