Human Gene Module / Chromosome Y / USP9Y

USP9Yubiquitin specific peptidase 9, Y-linked

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
1 / 1
Aliases
USP9Y, DFFRY,  SPGFY2
Associated Syndromes
-
Chromosome Band
Yq11.221
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the USP9Y gene and autism in an ACC cohort (Wang et al., 2009).

Molecular Function

This gene is a member of the peptidase C19 family. It encodes a protein that is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to USP9Y (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Common genetic variants on 5p14.1 associate with autism spectrum disorders Wang K , et al. (2009) Yes -
2 Support Neurogenetic analysis of childhood disintegrative disorder Gupta AR , et al. (2017) No -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.364C>T p.Arg122Ter stop_gained Familial Paternal Multi-generational 28392909 Gupta AR , et al. (2017)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.773+131A>C C/A intron_variant - - - 19404256 Wang K , et al. (2009)
SFARI Gene score
2

Strong Candidate

Genetic association has been found between the USP9Y gene and autism (P-value 0.0001045) in a case-control analysis utilizing the ACC cohort (Wang et al., 2009). A paternally-inherited nonsense variant in the USP9Y gene was identified in a male proband with childhood disintegrative disorder; the proband's father and paternal grandfather reportedly had high-functioning autism (Gupta et al., 2017).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Genetic association has been found between the USP9Y gene and autism (P-value 0.0001045) in a case-control analysis utilizing the ACC cohort (Wang et al., 2009). A paternally-inherited nonsense variant in the USP9Y gene was identified in a male proband with childhood disintegrative disorder; the proband's father and paternal grandfather reportedly had high-functioning autism (Gupta et al., 2017).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Genetic association has been found between the USP9Y gene and autism (P-value 0.0001045) in a case-control analysis utilizing the ACC cohort (Wang et al., 2009). A paternally-inherited nonsense variant in the USP9Y gene was identified in a male proband with childhood disintegrative disorder; the proband's father and paternal grandfather reportedly had high-functioning autism (Gupta et al., 2017).

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

Genetic association has been found between the USP9Y gene and autism (P-value 0.0001045) in a case-control analysis utilizing the ACC cohort (Wang et al., 2009). A paternally-inherited nonsense variant in the USP9Y gene was identified in a male proband with childhood disintegrative disorder; the proband's father and paternal grandfather reportedly had high-functioning autism (Gupta et al., 2017).

Krishnan Probability Score

Score 0.49178345835693

Ranking 5087/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.14070143795032

Ranking 7474/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Larsen Cumulative Evidence Score

Score 1

Ranking 438/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.036482768636148

Ranking 9914/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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