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
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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.
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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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Selective labelling of GBA2 in cells with fluorescent β-d-arabinofuranosyl cyclitol aziridines.
Su Q et al.·Chem Sci
2024Open Access
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
2024Open AccessReview
Mitochondrial dysfunction in NPC1-deficiency is not rescued by drugs targeting the glucosylceramidase GBA2 and the cholesterol-binding proteins TSPO and StARD1.
Wheeler S et al.·FEBS Lett
2024
Structural basis for inhibition of a GH116 β-glucosidase and its missense mutants by GBA2 inhibitors: Crystallographic and quantum chemical study.
Meelua W et al.·Chem Biol Interact
2023
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
2021
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