Human Gene Module / Chromosome Y / USP9Y

USP9Yubiquitin specific peptidase 9, Y-linked

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
1 / 1
Aliases
USP9Y, DFFRY,  SPGFY2
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
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.

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
3

Suggestive Evidence

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: Decreased from 4 to 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.

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]
4/1/2018
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4.3

Increased from to 4.3

Description

4

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.
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
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.
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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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