This report describes Parkinson disease 16 (PARK16), which is described as a susceptibility locus for Parkinson disease. The causative gene has not been identified; the region to which associated polymorphisms map contains 5 genes: SLC45A3, NUCKS1, RAB29, SLC41A1, and PM20D1.
Based on neurodegenerative phenotypes observed for the Drosophila Rab32 gene and genetic interactions with a gene modeling PARK8, it is postulated that RAB29 (RAB7L1 in OMIM), one of the human orthologs of Dmel\Rab32, is the causative gene for Parkinson disease 16 (FBrf0220738). This is supported by recent work using human cell lines that describes interactions between RAB29 and LRRK2 (Purlyte et al., 2018; pubmed:29212815); LRRK2 is implicated in Parkinson disease 8 (FBhh0000011).
The human RAB29 gene has not been introduced into flies. RAB29 is similar to the short isoforms of Dmel\Rab32; these consist only of the carboxy GTPase domain and lack the additional amino sequences found in longer isoforms.
[updated Mar. 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 16; PARK16](https://omim.org/entry/613164)
[PARKINSON DISEASE 16; PARK16](https://omim.org/entry/613164)
PARK16 is also described as a susceptibility locus.
RAB29 is associated with Parkinson disease in multiple GWAS studies (see GWAS Catalog, below in 'External links').
Mapped by statistical methods; causative gene has not been unambiguously identified. SNPs with significant associations to PD were found to lie within several linkage disequilibrium blocks containing 5 genes: SLC45A3, NUCKS1, RAB7L1, SLC41A1, and PM20D1. [from MIM:613164; 2015.07.27]
The shortest isoform of Dmel\Rab32 is comparable to human RAB32, RAB38 and RAB29 in length and consists almost entirely of a Rab GTPase domain; this isoform shares 51-65% identity and 71-77% similarity with the human genes. Of these 3 genes, only RAB29 maps in a region associated with Parkinson disease, in the region associated with PARK16.
