GBA1

Chr 1ADMultiAR

glucosylceramidase beta 1

Also known as: GBA, GCB, GLUC

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/Multi/ARLOEUF 0.807 OMIM phenotypes
Clinical SummaryGBA1
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Gene-Disease Validity (ClinGen)
Parkinson disease · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.000
Z-score 2.36
OE 0.51 (0.340.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.17Z-score
OE missense 0.81 (0.730.90)
248 obs / 305.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.340.80)
00.351.4
Missense OE0.81 (0.730.90)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 14 / 27.3Missense obs/exp: 248 / 305.8Syn Z: -0.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGBA1-related Gaucher disease perinatal lethalLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.4776th %ile
LOF
0.3065th %ile

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

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Idiopathic Parkinson's Disease (PD)

Study on the Incidence of Malignant Neoplasms in Patients with Parkinson's Disease and Heterozygous Mutation of the GBA Gene

RECRUITING
NCT06814431Azienda USL Reggio Emilia - IRCCSStarted 2023-11-23
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
Gaucher Disease

Screening for Gaucher Disease and Acid Sphingomyelinase Deficiency

NOT YET RECRUITING
NCT06258577Chung-Hsing WangStarted 2024-05-01
Gaucher Disease, Type 2

Phase 1/2 Clinical Trial of PR001 in Infants With Type 2 Gaucher Disease (PROVIDE)

ACTIVE NOT RECRUITING
NCT04411654Phase PHASE1, PHASE2Prevail TherapeuticsStarted 2021-06-29
LY3884961MethylprednisoloneSirolimus
Parkinson DiseaseGBA Gene MutationGaucher Disease

The GBA Multimodal Study in Parkinson's Disease

RECRUITING
NCT04101968Pacific Parkinson's Research CentreStarted 2019-05-01
PET scanneuroQWERTY
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

Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD

ACTIVE NOT RECRUITING
NCT05819359Phase PHASE2Bial R&D Investments, S.A.Started 2023-03-31
BIA 28-6156 10 mgBIA 28-6156 60 mgPlacebo
Parkinson DiseaseGaucher DiseaseHealthy

Drug Discovery for Parkinson's With Mutations in the GBA Gene

RECRUITING
NCT05536388New York Stem Cell Foundation Research InstituteStarted 2022-07-15
Biological Sample Collection
Parkinson Disease

Non Motor Symptoms in Glucocerebrosidase-related Parkinson's Disease

ENROLLING BY INVITATION
NCT06451419Juan Pablo Romero. MD, PhDStarted 2024-07-01
Tests on non motor symptoms
Monoclonal Gammopathy of Undetermined SignificanceMyeloma Multiple

Determine the Frequency of Variants in the GBA/PSAP Genes in Patients With MM or MGUS

NOT YET RECRUITING
NCT06559033University Hospital, RouenStarted 2025-06-01
Evaluation of the presence and number of mutated alleles of the GBA/PSAP genes in patients with MM or MGUS
Gaucher Disease Type 1

A Clinical Study Evaluating LY-M001 Injection in the Treatment of Adult Patients With Type I Gaucher Disease

RECRUITING
NCT06818838Phase PHASE1, PHASE2Lingyi Biotech Co., Ltd.Started 2024-07-05
LY-M001
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.
Clinical Literature
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