GBA2

Chr 9AR

glucosylceramidase beta 2

Also known as: AD035, NLGase, SPG46

NCBI Gene: 57704ENSG00000070610UniProt: Q9HCG7OMIM: 609471

The protein is a microsomal beta-glucosidase localized to the endoplasmic reticulum that catalyzes the hydrolysis of bile acid 3-O-glucosides. Biallelic mutations cause spastic paraplegia 46, an autosomal recessive hereditary spastic paraplegia. The pathogenic mechanism involves loss of function of this carbohydrate metabolism enzyme.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.941 OMIM phenotype
Clinical Summary— GBA2
🧬
Gene-Disease Validity (ClinGen)
complex hereditary spastic paraplegia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.91
OE 0.72 (0.56–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.67Z-score
OE missense 0.80 (0.74–0.87)
440 obs / 550.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.56–0.94)
0≤0.351.4
Missense OE0.80 (0.74–0.87)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 39 / 54.2Missense obs/exp: 440 / 550.1Syn Z: 0.94

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GBA2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Hereditary ataxias and paraparesias: clinical and genetic update.
Parodi L et al.·Curr Opin Neurol
2018Review
Spastic paraplegia type 46: novel and recurrent GBA2 gene variants in a compound heterozygous Italian patient with spastic ataxia phenotype.
Gatti M et al.·Neurol Sci
2021Review
Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature.
Cioffi E et al.·Neurogenetics
2024Review
Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations.
Woeste MA et al.·J Biol Chem
2019
Transcriptomic signatures in peripheral CD4(+)T-lymphocytes may reflect melanoma staging and immunotherapy responsiveness prior to ICI initiation.
Palli E et al.·Front Immunol
2025
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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