GBA2

Chr 9

glucosylceramidase beta 2

Also known as: AD035, NLGase, SPG46

NCBI Gene: 57704 ENSG00000070610 UniProt: Q9HCG7

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a microsomal beta-glucosidase that catalyzes the hydrolysis of bile acid 3-O-glucosides as endogenous compounds. Studies to determine subcellular localization of this protein in the liver indicated that the enzyme was mainly enriched in the microsomal fraction where it appeared to be confined to the endoplasmic reticulum. This putative transmembrane protein is thought to play a role in carbohydrate transport and metabolism. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 46, autosomal recessive

Clinical highlights

Gene-disease validity (ClinGen)

complex hereditary spastic paraplegia · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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