GBA1
Chr 1ADMultiARglucosylceramidase beta 1
Also known as: GBA, GCB, GLUC
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]
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
755 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 48 | 40 | 2 | 0 | 90 |
Likely Pathogenic | 114 | 158 | 5 | 0 | 277 |
VUS | 5 | 193 | 27 | 28 | 253 |
Likely Benign | 0 | 2 | 7 | 42 | 51 |
Benign | 0 | 1 | 5 | 0 | 6 |
Conflicting | — | 64 | |||
| Total | 167 | 394 | 46 | 70 | 741 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →19 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap GBA1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD
ACTIVE NOT RECRUITINGThe GBA Multimodal Study in Parkinson's Disease
RECRUITINGEffectiveness of Cognitive Stimulation Treatment in Patients With Parkinson's Disease
RECRUITINGPhase 1/2 Clinical Trial of PR001 in Infants With Type 2 Gaucher Disease (PROVIDE)
ACTIVE NOT RECRUITINGUnderstanding Alpha-Synuclein Spread in Parkinson's Disease Through Blood Biomarkers and Neuroimaging
NOT YET RECRUITINGMolecular and Functional Imaging in Monogenic PD.
RECRUITINGWorld Data on Ambroxol for Patients With GD and GBA Related PD
RECRUITINGNon Motor Symptoms in Glucocerebrosidase-related Parkinson's Disease
ENROLLING BY INVITATIONGenotypic Influences on Network Progression in Parkinson's Disease
ACTIVE NOT RECRUITINGScreening for Gaucher Disease and Acid Sphingomyelinase Deficiency
NOT YET RECRUITINGAn Exploratory Clinical Trial of VGN-R08b in Patients With Type II Gaucher Disease
RECRUITINGA 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 RECRUITINGExternal Resources
Links to major genomics databases and tools