The gene implicated in Parkinson disease subtype PARK21, a late-onset 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 TMEM230 in development of Parkinson disease.
TMEM230 encodes a transmembrane protein that localizes to secretory and recycling vesicle in the neuron and is postulated to be involved in synaptic vesicle trafficking and recycling. There is a single orthologous gene in Drosophila, CG2611, for which RNAi targeting constructs, overexpression constructs, and a CRISPR/Cas9-mediated knockout construct have been generated.
UAS constructs of the human Hsap\TMEM230 gene have been introduced into flies, including wild-type and variants implicated in development of Parkinson disease. See the 'Disease-Implicated Variants' table below. Neural expression of the more severe variants results in shortened lifespan and locomotor defects; one of these has been shown to induce progressive degeneration of dopaminergic neurons in the adult brain.
See also the human disease model report 'Parkinson disease (postulated), DNAJC13-related' (FBhh0001155).
[updated Jul. 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 disease characterized by tremor, rigidity, bradykinesia, postural instability, and good response to levodopa treatment (summary by Vilarino-Guell et al., 2014, pubmed:24218364). [from MIM:616361; 2022.07.19]
The molecular basis of this disease is unclear; mutations in 2 different genes, DNAJC13 and TMEM230, have been implicated. [from MIM:616361; 2022.07.19]
TMEM230 encodes a multi-pass transmembrane protein that localizes to secretory and recycling vesicle in the neuron; may be involved in synaptic vesicle trafficking and recycling. [Gene Cards, TMEM230; 2022.07.19]
One to one: 1 human gene to 1 Drosophila gene.
Moderate-scoring ortholog of human TMEM230 (1 Drosophila to 1 human).
