PRKNparkin RBR E3 ubiquitin protein ligase
Autism Reports / Total Reports
11 / 20Rare Variants / Common Variants
26 / 3Aliases
PRKN, AR-JP, LPRS2, PARK2, PDJAssociated Syndromes
-Chromosome Band
6q26Associated Disorders
IDRelevance to Autism
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
SFARI Genomic Platforms
Reports related to PRKN (20 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase | Shimura H , et al. (2000) | No | - |
| 2 | Highly Cited | Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease | Shimura H , et al. (2001) | No | - |
| 3 | Highly Cited | An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin | Imai Y , et al. (2001) | No | - |
| 4 | Recent Recommendation | Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein | Lu XH , et al. (2009) | No | - |
| 5 | Recent Recommendation | Identification of a novel Zn2+-binding domain in the autosomal recessive juvenile Parkinson-related E3 ligase parkin | Hristova VA , et al. (2009) | No | - |
| 6 | Primary | Autism genome-wide copy number variation reveals ubiquitin and neuronal genes | Glessner JT , et al. (2009) | Yes | - |
| 7 | Support | Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations | O'Roak BJ , et al. (2012) | Yes | - |
| 8 | Support | Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder | Jarick I , et al. (2012) | No | - |
| 9 | Support | A discovery resource of rare copy number variations in individuals with autism spectrum disorder | Prasad A , et al. (2013) | Yes | - |
| 10 | Support | Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder | Girirajan S , et al. (2013) | Yes | - |
| 11 | Support | Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders | Nava C , et al. (2013) | Yes | ID |
| 12 | Support | Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder | Yin CL , et al. (2016) | Yes | - |
| 13 | Support | Definition of a putative pathological region in PARK2 associated with autism spectrum disorder through in silico analysis of its functional structure | Conceio IC , et al. (2016) | Yes | - |
| 14 | Positive Association | Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts | Zhang X , et al. (2019) | No | - |
| 15 | Support | - | Xie X et al. (2022) | No | - |
| 16 | Support | - | Huo Y et al. (2022) | Yes | - |
| 17 | Support | - | Zhou X et al. (2022) | Yes | - |
| 18 | Negative Association | - | et al. () | Yes | - |
| 19 | Support | - | et al. () | Yes | - |
| 20 | Highly Cited | Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism | Kitada T , et al. (1998) | No | - |
Rare Variants (26)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | Unknown | - | - | 35707784 | Xie X et al. (2022) | |
| - | - | copy_number_loss | Unknown | - | Simplex | 23632794 | Nava C , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | Multiplex | 9560156 | Kitada T , et al. (1998) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_loss | Familial | Both parents | - | 35707784 | Xie X et al. (2022) | |
| - | - | copy_number_gain | De novo | - | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| c.850G>C | p.Gly284Arg | missense_variant | Unknown | - | Unknown | 38287090 | et al. () | |
| - | - | copy_number_gain | Familial | Paternal | Simplex | 27042285 | Yin CL , et al. (2016) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 27042285 | Yin CL , et al. (2016) | |
| - | - | copy_number_gain | Familial | Maternal | Multiplex | 23632794 | Nava C , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_gain | Unknown | Not maternal | Simplex | 27042285 | Yin CL , et al. (2016) | |
| - | - | copy_number_gain | Familial | Paternal | Simplex | 22495309 | O'Roak BJ , et al. (2012) | |
| - | - | copy_number_loss | Familial | Both parents | Simplex | 9560156 | Kitada T , et al. (1998) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 27824727 | Conceio IC , et al. (2016) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 27824727 | Conceio IC , et al. (2016) | |
| - | - | copy_number_gain | Familial | Maternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_gain | Familial | Paternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 27824727 | Conceio IC , et al. (2016) | |
| - | - | copy_number_gain | Familial | Paternal | Multiplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_loss | Familial | Paternal | Multiplex | 23375656 | Girirajan S , et al. (2013) | |
| c.882C>T | p.Pro294%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| - | - | copy_number_loss | Familial | Maternal | Multi-generational | 27824727 | Conceio IC , et al. (2016) |
Common Variants (3)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | - | - | - | 31003785 | Zhang X , et al. (2019) | |
| - | - | copy_number_loss | - | - | - | 19404257 | Glessner JT , et al. (2009) | |
| - | - | copy_number_variation | - | - | - | 23164820 | Jarick I , et al. (2012) |
SFARI Gene score
Strong Candidate
Deletions affecting PRKN (formerly known as PARK2) were observed in 7 cases (discovery and replication datasets) but not in controls (P=0.0047) in Glessner et al., 2009; 1/7 variants were confirmed by qPCR, but the status of the remainder is unknown (P value of 3.3 x 10-3 is for genes within GO term "ubiquitin conjugation", not PRKN alone), and gene-level statistical support was only nominal in this report. A total of 24 PRKN exon-disrupting CNVs (12 deletions, 12 duplications) were detected in a cohort of 2,588 ASD cases compared to a total of 10 exon-disrupting CNVs (5 deletions, 5 duplications) in 2670 controls (p=0.009) in Girirajan et al. 2013. A genome-wide analysis of CNVs in a Han Chinese ASD cohort in Yin et al., 2016 determined that the frequency of exonic CNVs at the PRKN locus was significantly greater in ASD cases (6/636) than in ethnically-matched controls (2/1394; P=0.014). Comparison of the frequencies of PRKN CNVs in NDD cases and controls in Conceicao et al., 2016 demonstrated that NDD patients had a higher frequency of CNVs containing exons 5-12 of the PRKN gene (26.8%) than did controls (2.4%; P=0.0003). However, in many cases PRKN CNVs from these studies were predominantly inherited and displayed incomplete penetrance with ASD. CNVs within the PRKN locus were also found to be significantly more prevalent in German ADHD patients in both discovery (P=2.8E-04) and replication (P=4.3E-2) samples than in controls (Jarick et al., 2014). OMIM indicates that autosomal recessive mutations in this gene result in juvenile onset Parkinsons disease. A meta-analysis of 5,780 cases with major depressive disorder (MDD) and 6,626 controls from four cohorts in Zhang et al., 2019 identified a CNV region containing exonic and intronic deletions in the PRKN gene that was statistically enriched in MDD cases compared with controls (65 in cases vs. 40 in controls; odds ratio 1.92, P-value 9.7E-04).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
10/1/2019
Decreased from 3 to 2
New Scoring Scheme
Description
Deletions affecting PRKN (formerly known as PARK2) were observed in 7 cases (discovery and replication datasets) but not in controls (P=0.0047) in Glessner et al., 2009; 1/7 variants were confirmed by qPCR, but the status of the remainder is unknown (P value of 3.3 x 10-3 is for genes within GO term "ubiquitin conjugation", not PRKN alone), and gene-level statistical support was only nominal in this report. A total of 24 PRKN exon-disrupting CNVs (12 deletions, 12 duplications) were detected in a cohort of 2,588 ASD cases compared to a total of 10 exon-disrupting CNVs (5 deletions, 5 duplications) in 2670 controls (p=0.009) in Girirajan et al. 2013. A genome-wide analysis of CNVs in a Han Chinese ASD cohort in Yin et al., 2016 determined that the frequency of exonic CNVs at the PRKN locus was significantly greater in ASD cases (6/636) than in ethnically-matched controls (2/1394; P=0.014). Comparison of the frequencies of PRKN CNVs in NDD cases and controls in Conceicao et al., 2016 demonstrated that NDD patients had a higher frequency of CNVs containing exons 5-12 of the PRKN gene (26.8%) than did controls (2.4%; P=0.0003). However, in many cases PRKN CNVs from these studies were predominantly inherited and displayed incomplete penetrance with ASD. CNVs within the PRKN locus were also found to be significantly more prevalent in German ADHD patients in both discovery (P=2.8E-04) and replication (P=4.3E-2) samples than in controls (Jarick et al., 2014). OMIM indicates that autosomal recessive mutations in this gene result in juvenile onset Parkinsons disease. A meta-analysis of 5,780 cases with major depressive disorder (MDD) and 6,626 controls from four cohorts in Zhang et al., 2019 identified a CNV region containing exonic and intronic deletions in the PRKN gene that was statistically enriched in MDD cases compared with controls (65 in cases vs. 40 in controls; odds ratio 1.92, P-value 9.7E-04).
Reports Added
[New Scoring Scheme]4/1/2019
Decreased from 3 to 3
Description
Deletions affecting PRKN (formerly known as PARK2) were observed in 7 cases (discovery and replication datasets) but not in controls (P=0.0047) in Glessner et al., 2009; 1/7 variants were confirmed by qPCR, but the status of the remainder is unknown (P value of 3.3 x 10-3 is for genes within GO term "ubiquitin conjugation", not PRKN alone), and gene-level statistical support was only nominal in this report. A total of 24 PRKN exon-disrupting CNVs (12 deletions, 12 duplications) were detected in a cohort of 2,588 ASD cases compared to a total of 10 exon-disrupting CNVs (5 deletions, 5 duplications) in 2670 controls (p=0.009) in Girirajan et al. 2013. A genome-wide analysis of CNVs in a Han Chinese ASD cohort in Yin et al., 2016 determined that the frequency of exonic CNVs at the PRKN locus was significantly greater in ASD cases (6/636) than in ethnically-matched controls (2/1394; P=0.014). Comparison of the frequencies of PRKN CNVs in NDD cases and controls in Conceicao et al., 2016 demonstrated that NDD patients had a higher frequency of CNVs containing exons 5-12 of the PRKN gene (26.8%) than did controls (2.4%; P=0.0003). However, in many cases PRKN CNVs from these studies were predominantly inherited and displayed incomplete penetrance with ASD. CNVs within the PRKN locus were also found to be significantly more prevalent in German ADHD patients in both discovery (P=2.8E-04) and replication (P=4.3E-2) samples than in controls (Jarick et al., 2014). OMIM indicates that autosomal recessive mutations in this gene result in juvenile onset Parkinsons disease.
7/1/2018
Increased from to 3
Description
Deletions affecting PRKN (formerly known as PARK2) were observed in 7 cases (discovery and replication datasets) but not in controls (P=0.0047) in Glessner et al., 2009; 1/7 variants were confirmed by qPCR, but the status of the remainder is unknown (P value of 3.3 x 10-3 is for genes within GO term "ubiquitin conjugation", not PRKN alone), and gene-level statistical support was only nominal in this report. A total of 24 PRKN exon-disrupting CNVs (12 deletions, 12 duplications) were detected in a cohort of 2,588 ASD cases compared to a total of 10 exon-disrupting CNVs (5 deletions, 5 duplications) in 2670 controls (p=0.009) in Girirajan et al. 2013. A genome-wide analysis of CNVs in a Han Chinese ASD cohort in Yin et al., 2016 determined that the frequency of exonic CNVs at the PRKN locus was significantly greater in ASD cases (6/636) than in ethnically-matched controls (2/1394; P=0.014). Comparison of the frequencies of PRKN CNVs in NDD cases and controls in Conceicao et al., 2016 demonstrated that NDD patients had a higher frequency of CNVs containing exons 5-12 of the PRKN gene (26.8%) than did controls (2.4%; P=0.0003). However, in many cases PRKN CNVs from these studies were predominantly inherited and displayed incomplete penetrance with ASD. CNVs within the PRKN locus were also found to be significantly more prevalent in German ADHD patients in both discovery (P=2.8E-04) and replication (P=4.3E-2) samples than in controls (Jarick et al., 2014). OMIM indicates that autosomal recessive mutations in this gene result in juvenile onset Parkinsons disease.