Human Gene Module / Chromosome 1 / USP24

USP24ubiquitin specific peptidase 24

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
6 / 12
Rare Variants / Common Variants
9 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
1p32.3
Associated Disorders
-
Relevance to Autism

Genome sequencing of 50 ASD probands and their unaffected parents from a Qatari cohort in Ben-Mahmoud et al., 2024 identified a de novo missense variant in the USP24 gene that was not in gnomAD or the Qatar Genome Project and was predicted to be damaging with a CADD score of 28.2 in a male ASD proband. Five de novo missense variants (four of which had CADD scores > 25) and three de novo coding-synonymous variants in the USP24 gene were previously identified in ASD probands (Iossifov et al., 2014; Satterstrom et al., 2020; Zhou et al., 2022; Fu et al., 2022; Yuan et al., 2023).

Molecular Function

Modification of cellular proteins by ubiquitin is an essential regulatory mechanism controlled by the coordinated action of multiple ubiquitin-conjugating and deubiquitinating enzymes. USP24 belongs to a large family of cysteine proteases that function as deubiquitinating enzymes. A number of studies have suggested an association between the USP24 gene, which lies within the PARK10 locus, and Parkinson disease (Oliveira et al., 2005; Li et al, 2006, Haugarvoll et al., 2009; Wu et al., 2010).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to USP24 (12 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association - Sofia A Oliveira et al. (2005) No -
2 Positive Association - Yonghong Li et al. (2006) No -
3 Positive Association - Kristoffer Haugarvoll et al. (2009) No -
4 Positive Association - Yih-Ru Wu et al. (2010) No -
5 Negative Association - Bi Zhao et al. (2012) No -
6 Negative Association - Jia Y Wan et al. (2014) No -
7 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
8 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
9 Support - Zhou X et al. (2022) Yes -
10 Support - Fu JM et al. (2022) Yes -
11 Support - Yuan B et al. (2023) Yes -
12 Primary - Afif Ben-Mahmoud et al. (2024) Yes DD
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.5368A>C p.Lys1790Gln missense_variant De novo - - 35982160 Fu JM et al. (2022)
c.5215T>A p.Phe1739Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3245T>A p.Val1082Glu missense_variant De novo - - 36881370 Yuan B et al. (2023)
c.4614T>C p.Leu1538= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.7518T>G p.Leu2506= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.4984A>G p.Met1662Val missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.3435A>T p.Ser1145= synonymous_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.3497C>T p.Ala1166Val missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.70C>G p.Arg24Gly missense_variant De novo - Simplex 39519104 Afif Ben-Mahmoud et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

criteria met
See SFARI Gene'scoring criteria
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.

10/1/2024
3

Initial score established: 3

Krishnan Probability Score

Score 0.47901416856563

Ranking 8208/25841 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 0.99999999849647

Ranking 106/18225 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 0.94113748771731

Ranking 14822/18665 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 -0.20091746319706

Ranking 15448/20870 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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