Human Gene Module / Chromosome 6 / PRKN

PRKNparkin RBR E3 ubiquitin protein ligase

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
7 / 15
Rare Variants / Common Variants
22 / 3
Aliases
PRKN, AR-JP,  LPRS2,  PARK2,  PDJ
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
6q26
Associated Disorders
ID
Relevance 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.

Reports related to PRKN (15 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... 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 insilico 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 Highly Cited Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Kitada T , et al. (1998) No -
Rare Variants   (22)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Simplex 23632794 Nava C , et al. (2013)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_gain De novo - Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Paternal Simplex 27042285 Yin CL , et al. (2016)
- - copy_number_loss Familial Paternal Multiplex 9560156 Kitada T , et al. (1998)
- - 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)
- - copy_number_gain Familial Paternal Multi-generational 27042285 Yin CL , et al. (2016)
- - 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
3

Suggestive Evidence

3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2018

Initial score established:

Description

3

CNVs associated with PRKN(1 CNVs)
6q26 36 Deletion-Duplication 61  /  319
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