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FB2026_01
,
released March 12, 2026
The gene implicated in Parkinson disease subtype PARK21, an autosomal dominant form of the disease, has not been definitively identified; both DNAJC13 and TMEM230 have been implicated. This report describes work in Drosophila investigating the possible role of DNAJC13 in development of Parkinson disease.
DNAJC13 encodes a member of the DnaJ protein family; it plays a role in clathrin-mediated endocytosis and endosomal trafficking. There is a single orthologous gene in Drosophila, Rme-8, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs of the human Hsap\DNAJC13 gene have been introduced in to flies, including the wild-type gene and a gene carrying a variant implicated in this disease (see the 'Disease-Implicated Variants' table below). Variant(s) implicated in human disease tested (as transgenic human gene, DNAJC13): the N855S variant form has been introduced into flies. Expression of this variant in the fly eye results in a mild rough eye phenotype; expression of wild-type Hsap\DNAJC13 fails to produce this phenotype. Co-expression of the Hsap\DNAJC13 variant with Hsap\SNCA exacerbates the Hsap\SNCA phenotypes (see the human disease model report 'Parkinson 1' FBhh0000006).
Animals homozygous for loss-of-function mutations of Rme-8 typically die during the larval stage. Physical and genetic interactions have been described for Dmel\Rme-8; see below and in the Rme-8 gene report.
[updated Feb. 2022 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 21; PARK21](https://omim.org/entry/616361)
[PARKINSON DISEASE 21; PARK21](https://omim.org/entry/616361)
Parkinson disease-21 (PARK21) is an autosomal dominant form of typical adult-onset Parkinson.
The molecular basis of this disease is unclear; mutations in 2 different genes, DNAJC13 and TMEM230, have been implicated.
DNAJC13 encodes a member of the DnaJ protein family whose members act as co-chaperones of a partner heat-shock protein by binding to the latter and stimulating ATP hydrolysis. Specifically, the DNAJC13 protein appears to play roles in clathrin-mediated endocytosis, membrane trafficking through early endosomes, and vesicle formation and trafficking within the endosomal system. [Gene Cards, DNAJC13, 2019.12.09; MARRVEL, DNAJC13, 2019.12.09]
The endocytic membrane-trafficking pathway and disruption of synaptic vesicle endocytosis appear to play major roles in the risk of Parkinson disease. A substantial amount of genetic variation in PD and parkinsonism has been associated with vesicle trafficking via endosomal gene alterations. (Bandres-Ciga et al., 2019, pubmed:30675927; Nguyen et al., 2019, pubmed:30509690). Relevant genes include DNAJC6 (see FBhh0000594, FBhh0000593), SYNJ1 (see FBhh0000626), GAK (see FBhh0000593) and SH3GL2, which are linked to clathrin-coated vesicles, and VPS35 (see FBhh0000030) and DNAJC13 (see FBhh0001155), which participate in recycling components from the endosomes to the Golgi. In addition, LRRK2 (see FBhh0000011) and PLA2G6 (see FBhh0000243, FBhh0000232) have been shown to interact with genes involved in endocytic membrane trafficking.
One-to-one: 1 human to 1 Drosophila.
High-scoring ortholog of human DNAJC13 (1 Drosophila to 1 human). Dmel\Rme-8 shares 46% identity and 64% similarity with the human gene.