In a genome-wide study, association was found between CNVs in the PRKN gene and autism in AGRE and ACC cohorts (European ancestry) (Glessner et al., 2009). In addition, a rare duplication in the PRKN gene has been identified in an individual with ASD (ORoak et al., 2012). As well, rare variants in the PRKN gene have been identified in individuals with autosomal recessive juvenile parkinsonism (Kitada et al., 1998).
Molecular Function
The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Zinc finger nuclease-directed 5-base pair deletion in exon 4 that results in a frameshift mutation.
Allele Type: Knockout
Strain of Origin: Genetic Background: Long Evans
ES Cell Line: Mutant ES Cell Line: Model Source: SAGE Labs
Description: Locomotor response in response to 2 mg/kg methamphetamine was significantly lower in Parkin knockouts compared to controls.
Exp Paradigm: Injected intraperitoneally with 2 mg/kg methamphetamine, and activity measured for 100 min.
Description: Similar levels of alpha-tubulin and beta-actin were found in cell lysates and whole synaptosomal fractions, however, beta-actin immunoreactivity was higher in the membrane-endosomal fraction and lower in the cytosol-vesicular fraction. Similar trends were seen for alpha-tubulin, but the changes did not reach statistical significance.
Exp Paradigm: Synaptosomal fractionation followed by Western blot with beta-actin and alpha-tubulin antibodies
Description: TAAR-1 localizes intracellularly in presynaptic and postsynaptic neuronal elements. The immunoreactivity of the 56-kDa band was unchanged in the cerebellum of Parkin knockout rats compared to wildtype rats.
Description: Compared to the wildtype controls, the levels of D2L receptor were significantly decreased in striatal lysates from the Parkin knockout rats. Total levels of D2 receptor (S + L) were unchanged.
Description: The levels of beta-PEA, a trace amine neuromodulator, were significantly higher in the striatum from the Parkin knockout rats compared to the wildtype rats.
Description: Small stereotypic movements including grooming measured within 30 min time frame were significantly decreased in Parkin knockout rats compared to controls.
Description: The 70 kDa band may be a complex of TDP-43 with one of its interacting protein partners. The 70 kDa band was of lower density in the Parkin knockout rats compared to the controls.
Description: Drd2 mRNA was significantly increased in Parkin knockout rats compared to wildtype.
Exp Paradigm: Quantitaive PCR using Chrna7 as control.
Description: Monoamine oxidase A (metabolizing dopamine) and monoamine oxidase B (metabolizing beta-PEA) show significantly reduced activity in Parkin knockout striata, with no difference in protein levels of these enzymes.
