GBA mutated E326K

Function

Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramide/GlcCer into free ceramide and glucose (PubMed:9201993, PubMed:24211208, PubMed:15916907). Thereby, plays a central role in the degradation of complex lipids and the turnover of cellular membranes (PubMed:27378698). Through the production of ceramides, participates in the PKC-activated salvage pathway of ceramide formation (PubMed:19279011). Also plays a role in cholesterol metabolism (PubMed:24211208, PubMed:26724485). May either catalyze the glucosylation of cholesterol, through a transglucosylation reaction that transfers glucose from glucosylceramide to cholesterol (PubMed:24211208, PubMed:26724485). The short chain saturated C8:0-GlcCer and the mono-unsaturated C18:0-GlcCer being the most effective glucose donors for that transglucosylation reaction (PubMed:24211208). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl-beta-D-glucoside to ceramide (PubMed:26724485). Finally, may also hydrolyze cholesteryl-beta-D-glucoside to produce D-glucose and cholesterol (PubMed:24211208, PubMed:26724485).

Involvement in disease

Gaucher disease

GD

A lysosomal storage disease due to deficient activity of beta-glucocerebrosidase and characterized by accumulation of glucosylceramide in the reticulo-endothelial system. Different clinical forms are recognized depending on the presence (neuronopathic forms) or absence of central nervous system involvement, severity and age of onset.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 1

GD1

A form of Gaucher disease characterized by hepatosplenomegaly with consequent anemia and thrombopenia, and bone involvement. The central nervous system is not involved.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 2

GD2

The most severe form of Gaucher disease. It manifests soon after birth, with death generally occurring before patients reach two years of age.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 3

GD3

A subacute form of neuronopathic Gaucher disease. It has later onset and slower progression compared to the acute form of neuronopathic Gaucher disease 2.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease 3C

GD3C

A variant of subacute neuronopathic Gaucher disease 3 associated with cardiovascular calcifications.

None

The disease is caused by variants affecting the gene represented in this entry.

Gaucher disease perinatal lethal

GDPL

Distinct form of Gaucher disease type 2, characterized by fetal onset. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurologic involvement begins in the first week and leads to death within 3 months. Hepatosplenomegaly is a major sign, and is associated with ichthyosis, arthrogryposis, and facial dysmorphism.

None

The disease is caused by variants affecting the gene represented in this entry. Perinatal lethal Gaucher disease is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.

Parkinson disease

PARK

A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.

None

Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Pathway

Steroid metabolism; cholesterol metabolism.

Sphingolipid metabolism.

Sequence similarities

Belongs to the glycosyl hydrolase 30 family.

Cellular localization

• Lysosome membrane
• Peripheral membrane protein
• Lumenal side
• Interaction with saposin-C promotes membrane association (PubMed:10781797). Targeting to lysosomes occurs through an alternative MPR-independent mechanism via SCARB2 (PubMed:18022370).

Alternative names

• Lysosomal acid glucosylceramidase
• Lysosomal acid GCase
• Acid beta-glucosidase
• Alglucerase
• Beta-glucocerebrosidase
• Cholesterol glucosyltransferase
• Cholesteryl-beta-glucosidase
• D-glucosyl-N-acylsphingosine glucohydrolase
• Imiglucerase
• Beta-GC
• SGTase
• GBA1
• GBA
• GC
• GLUC

Database links

• swissprot:P04062

Target type

Proteins