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FB2026_01
,
released March 12, 2026
There is significant support for identification of the human GBA1 gene as a susceptibility locus for the development of late-onset Parkinson disease. GBA1 encodes the lysosomal membrane protein glucosylceramidase beta, which is required for glycolipid metabolism. There are two fly orthologs, Gba1a and Gba1b, for which amorphic alleles generated by targeted recombination, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human Hsap\GBA1 is implicated in multiple forms of Gaucher disease (MIM:606463, FBhh0000227). A number of the Gaucher-disease-associated variants of GBA1 are also associated with increased risk of Parkinson disease; co-occurrence has been observed.
Multiple UAS constructs of the human Hsap\GBA1 gene have been introduced into flies, including wild-type and genes carrying mutations associated with Gaucher disease and Parkinson disease. Heterologous rescue (functional complementation) has been demonstrated for glial-specific knockdown of Gba1b. Variant(s) implicated in human disease tested (as transgenic human gene, GBA1): the L444P (L483P) variant form and the N370S (N409S) variant form have been introduced into flies; both of these variants are associated with both Gaucher disease and increased risk of Parkinson disease. See the 'Disease-Implicated Variants' table below.
Animals homozygous for an amorphic allele of Dmel\Gba1b have been used to characterize cellular phenotypes associated with neurodegenerative protein aggregation; changes in the turnover and abundance of proteins associated with extracellular vesicles are observed. Animals carrying mutations in both fly genes, Gba1a and Gba1b, have been used to model Gaucher disease. A small number of genetic and physical interactions have been described; see below and in the Gba1a and Gba1b gene reports.
[updated Jan. 2019 by FlyBase; FBrf0222196]
Parkinson disease (PD) is a neurodegenerative disease usually typified by slow onset in mid to late adulthood; there are also early-onset and juvenile forms of the disease. Symptoms worsen over time and include resting tremor, muscular rigidity, bradykinesia [abnormal slowness of movement], and postural instability [impaired balance and coordination]; additional symptoms may include postural abnormalities, dysautonomia [symptoms caused by malfunction of the autonomic nervous system], dystonic cramps, and dementia. Parkinson disease is the second-most common neurodegenerative disease (after Alzheimer disease), affecting approximately 1% of the population over 50 (Polymeropoulos et al., 1996, pubmed:8895469). [from MIM:168600; 2013.07.23]
Parkinson disease is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 may be referred to as juvenile-onset disease. [from Genetics Home Reference, GHR_condition:parkinson-disease, 2015.02.13]
[PARKINSON DISEASE, LATE-ONSET; PD](https://omim.org/entry/168600)
[GLUCOSIDASE, BETA, ACID; GBA](https://omim.org/entry/606463)
[ALCOHOL DEHYDROGENASE 1C, GAMMA POLYPEPTIDE; ADH1C](https://omim.org/entry/103730)
[TATA BOX-BINDING PROTEIN; TBP](https://omim.org/entry/600075)
[ATAXIN 2; ATXN2](https://omim.org/entry/601517)
[ATAXIN 8 OPPOSITE STRAND; ATXN8OS](https://omim.org/entry/603680)
[ATAXIN 3; ATXN3](https://omim.org/entry/607047)
[MICROTUBULE-ASSOCIATED PROTEIN TAU; MAPT](https://omim.org/entry/157140)
Susceptibility to the development of the late-onset form of Parkinson disease has been associated with polymorphisms or mutations in several genes, including GBA. [from MIM:168600; 2017.09.22]
Several specific variants of GBA have been associated with susceptibility to late-onset Parkinson disease. [from MIM:168600, MIM:606463; 2017.09.22]
An extensive discussion can be found in MIM:168600, in the section "Association with the Glucocerebrosidase (GBA) Gene."
GBA (Glucosylceramidase Beta) encodes a lysosomal membrane protein that cleaves the beta-glucosidic linkage of glycosylceramide, an intermediate in glycolipid metabolism. [from Gene Cards, GBA; 2017.09.22]
One to many: 1 human to 2 Drosophila.
High-scoring ortholog of human GBA (2 Drosophila to 1 human). Dmel\Gba1b shares 32% identity and 50% similarity with human GBA.