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FB2026_01
,
released March 12, 2026
This report describes Parkinson disease 13 (PARK13), which is described as a susceptibility locus for Parkinson disease. The human gene implicated in this disease has been tentatively identified as HTRA2, which is a mitochondrial serine protease postulated to be involved in the cellular stress response. There is a single high-scoring fly ortholog, HtrA2, for which for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
A UAS construct of the wild-type human Hsap\HTRA2 gene has been introduced into flies. It has been used to characterize interactions with Hsap\SNCA in a Drosophila model of Parkinson disease 1 (FBhh0000006).
Variant(s) implicated in human disease tested (as analogous mutation in fly gene): G363S in the fly HtrA2 gene (corresponds to G399S in the human HTRA2 gene). Results in flies do not support the hypothesis that the G399S variant is a pathogenic variant.
Animals carrying amorphic mutations of Dmel\HtrA2 are viable, but are male sterile, with a reduced lifespan. Genetic and physical interactions have been characterized; see below and in the gene report for HtrA2. Interactions of Drosophila orthologs may support the hypothesis that mutations in the human HTRA2 gene confer susceptibility to Parkinson disease, but interpretations vary. It is postulated that Dmel\HtrA2 acts functionally downstream of Dmel\Pink1, in a parallel pathway that is independent of the Dmel\park pathway.
[updated Jun. 2020 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 13, AUTOSOMAL DOMINANT, SUSCEPTIBILITY TO; PARK13](https://omim.org/entry/610297)
[HTRA SERINE PEPTIDASE 2; HTRA2](https://omim.org/entry/606441)
Unconfirmed sub-type of Parkinson disease.
Parkinson disease 13 is characterized by typical symptoms of Parkinson disease (described above). [from MIM:610297; 2015.02.16]
Inherited as an autosomal dominant. Originally described as a sub-type of Parkinson disease associated with mutations in the HTRA2 gene (Strauss et al., 2005, pubmed:15961413), this finding has been questioned (Simon-Sanchez and Singleton, 2008, pubmed:18364387). [from MIM:610297; 2015.02.16]
The HTRA2 gene encodes a serine protease that localizes predominantly to the mitochondrial intermembrane space; it may play a role in mitochondrial protein quality control (Radke et al., 2008, pubmed:18362145). Following apoptotic stimuli, HTRA2 can interact with inhibitor of apoptosis protein (IAP), thus mediating cell death, or can mediate cell death via its serine protease activity (Suzuki et al., 2001, pubmed:11583623). [from MIM:606441; 2015.02.16]
Many to one: 4 human to 1 Drosophila; additional more distantly related gene(s) in both species.
Ortholog of human HTRA2, HTRA1, HTRA3, and HTRA4 (1 Drosphila to 4 human; additional more distantly related gene(s) in both species). Dmel\HtrA2 shares 45% identity and 63% similarity with human HTRA2, 41% identity and 60% similarity with human HTRA1, 40% identity and 60% similarity with human HTRA3 (one domain not in common), 45% identity and 66% similarity with human HTRA4 (one domain not in common).