GBA1 (P04062) variants and mutations

GBA1 (also known as P04062) is a human protein-coding gene encoding a lysosomal acid glucosylceramidase protein. It degrades glucosylceramide within lysosomes and is essential for normal sphingolipid turnover. Biallelic pathogenic variants cause Gaucher disease, while heterozygous pathogenic variants are among the strongest genetic risk factors for Parkinson disease. This analysis covers 987 GBA1 variants and mutations. Of these, 28% have pathogenic or likely pathogenic clinical classifications, 79% have computational variant effect predictions from REVEL and MutPred, and 62% have population-specific frequency data. Disease context includes Gaucher disease type 1, Gaucher disease, and Gaucher disease type 2. Example GBA1 variants include E2D, F3S, and S4P.

Variant analysis overview

Gene: GBA1
Protein: P04062
UniProt accession: P04062
Organism: Homo sapiens
Variants analyzed: 987
Variant scope: all variants
Completed: 2026-08-10

Variant and mutation evidence

Variant composition: 748 unspecified-consequence records; 111 synonymous variants; 99 missense variants; 14 frameshift variants; 6 splice-region variants; 5 stop-gained variants; 3 in-frame deletions; 1 in-frame insertions
Clinical classifications: 274 pathogenic or likely pathogenic; 9 benign or likely benign; 131 uncertain-significance; 1 conflicting; 60 other clinical labels.
Computational signals: 256 REVEL high-risk; 65 MutPred high-risk.
Variant classes: 815 missense; 111 synonymous; 60 truncating or splice.
Prediction scores: 782 variants have prediction scores (79% of the analyzed set).

Clinical, disease, and population context

Clinical evidence: 74 records have expert-only or criteria-backed evidence.
Clinical annotations: 475 variants have clinical annotations.
Population evidence: 677 variants have population-frequency evidence.
Disease context: 25 disease associations are represented. Top associations: Gaucher disease type 1, Gaucher disease, Gaucher disease type 2, Gaucher disease type 3, Gaucher disease type I, Gaucher disease type II, Gaucher disease perinatal lethal, Gaucher disease type III, Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome, Gaucher disease - ophthalmoplegia - cardiovascular calcification, GD1, GD2.

Protein structure and variant hotspots

Protein features: 5 post-translational modification sites.
Ancestry evidence: 609 variants have ancestry-specific frequency data.
PTM context: 9 variants overlap post-translational modification sites.
3D hotspots: 3 hotspot clusters were identified. Clusters at residues 122-419 (mixed, 30 variants); residues 166-433 (mixed, 11 variants); residues 483-528 (intolerant, 16 variants).
Allosteric analysis: 2 functional sites were identified.
gnomAD gene constraint: pLI 0.00 (tolerant of loss-of-function variation); LOEUF 0.50; missense Z-score 2.88.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable GBA1 variants

Examples include E2D, F3S, S4P, S5N, R8K, R8T, E9D, P12S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

GBA1 analysis run — GBA1 (987 variants) — completed 2026-08-10