Human Gene Module / Chromosome 6 / USP45

USP45Ubiquitin specific peptidase 45

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 7
Rare Variants / Common Variants
8 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
6q16.2
Associated Disorders
-
Relevance to Autism

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Molecular Function

The protein encoded by this gene acts catalyzes the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to USP45 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support - Rhine CL et al. (2022) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
7 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.478+1784C>A - intron_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1953C>A p.Tyr651Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1888A>G p.Met630Val missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.743C>A p.Pro248His missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2089C>T p.Arg697Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.223C>T p.Gln75Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2073+1G>T - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1965del p.Ser656ValfsTer7 frameshift_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2015
icon
3

Increased from to 3

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Krishnan Probability Score

Score 0.36684039847674

Ranking 23799/25841 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 8.697491637877E-14

Ranking 17513/18225 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
Sanders TADA Score

Score 0.067918018139675

Ranking 53/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.39510764541153

Ranking 1517/20870 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
Submit New Gene

Report an Error