Human Gene Module / Chromosome 20 / DUSP15

DUSP15dual specificity phosphatase 15

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 7
Rare Variants / Common Variants
8 / 2
Aliases
DUSP15, C20orf57,  VHY
Associated Syndromes
-
Chromosome Band
20q11.21
Associated Disorders
-
Relevance to Autism

A de novo missense variant in the DUSP15 gene that was predicted to be damaging was identified in an ASD proband in Neale et al., 2012; a second de novo missense variant in this gene that was predicted to be disease causing by MutationTaster was identified in an ASD proband of Chinese Han descent in Tian et al., 2016. An assocation study consisting of 255 children with ASD and 427 ethnically-matched healthy controls in Tian et al., 2016 also identified association of the DUSP15 intronic SNP rs37466599 with autism under allelic (P=0.0018), additive (P=0.001), and dominant (P=0.007) models.

Molecular Function

The protein encoded by this gene has both protein-tyrosine phophatase activity and serine/threonine-specific phosphatase activity, and therefore is known as a dual specificity phosphatase. This protein may function in the differentiation of oligodendrocytes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DUSP15 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Patterns and rates of exonic de novo mutations in autism spectrum disorders Neale BM , et al. (2012) Yes -
2 Primary Association of oligodendrocytes differentiation regulator gene DUSP15 with autism Tian Y , et al. (2016) Yes -
3 Support Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains Geisheker MR , et al. (2017) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Positive Association - Fang F et al. (2021) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.166G>A p.Ala56Thr missense_variant De novo - - 27223645 Tian Y , et al. (2016)
c.546C>T p.Thr182%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.320C>T p.Thr107Met missense_variant De novo - - 22495311 Neale BM , et al. (2012)
c.46A>G p.Lys16Glu missense_variant Unknown - - 28628100 Geisheker MR , et al. (2017)
c.7G>A p.Val3Met missense_variant Familial Maternal - 28628100 Geisheker MR , et al. (2017)
c.26G>A p.Arg9Gln missense_variant Familial Maternal - 28628100 Geisheker MR , et al. (2017)
c.386dup p.Gly131ArgfsTer77 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.218_219del p.Arg73ProfsTer134 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.628+19T>C - intron_variant - - - 34257739 Fang F et al. (2021)
c.628+19T>C - intron_variant - - - 27223645 Tian Y , et al. (2016)
SFARI Gene score
2

Strong Candidate

A de novo missense variant in the DUSP15 gene that was predicted to be damaging was identified in an ASD proband in Neale et al., 2012; a second de novo missense variant in this gene that was predicted to be disease causing by MutationTaster was identified in an ASD proband of Chinese Han descent in Tian et al., 2016. An assocation study consisting of 255 children with ASD and 427 ethnically-matched healthy controls in Tian et al., 2016 also identified association of the DUSP15 intronic SNP rs37466599 with autism under allelic (P=0.0018), additive (P=0.001), and dominant (P=0.007) models.

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

A de novo missense variant in the DUSP15 gene that was predicted to be damaging was identified in an ASD proband in Neale et al., 2012; a second de novo missense variant in this gene that was predicted to be disease causing by MutationTaster was identified in an ASD proband of Chinese Han descent in Tian et al., 2016. An assocation study consisting of 255 children with ASD and 427 ethnically-matched healthy controls in Tian et al., 2016 also identified association of the DUSP15 intronic SNP rs37466599 with autism under allelic (P=0.0018), additive (P=0.001), and dominant (P=0.007) models.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo missense variant in the DUSP15 gene that was predicted to be damaging was identified in an ASD proband in Neale et al., 2012; a second de novo missense variant in this gene that was predicted to be disease causing by MutationTaster was identified in an ASD proband of Chinese Han descent in Tian et al., 2016. An assocation study consisting of 255 children with ASD and 427 ethnically-matched healthy controls in Tian et al., 2016 also identified association of the DUSP15 intronic SNP rs37466599 with autism under allelic (P=0.0018), additive (P=0.001), and dominant (P=0.007) models.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo missense variant in the DUSP15 gene that was predicted to be damaging was identified in an ASD proband in Neale et al., 2012; a second de novo missense variant in this gene that was predicted to be disease causing by MutationTaster was identified in an ASD proband of Chinese Han descent in Tian et al., 2016. An assocation study consisting of 255 children with ASD and 427 ethnically-matched healthy controls in Tian et al., 2016 also identified association of the DUSP15 intronic SNP rs37466599 with autism under allelic (P=0.0018), additive (P=0.001), and dominant (P=0.007) models.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2017
4
icon
4

Decreased from 4 to 4

Description

A de novo missense variant in the DUSP15 gene that was predicted to be damaging was identified in an ASD proband in Neale et al., 2012; a second de novo missense variant in this gene that was predicted to be disease causing by MutationTaster was identified in an ASD proband of Chinese Han descent in Tian et al., 2016. An assocation study consisting of 255 children with ASD and 427 ethnically-matched healthy controls in Tian et al., 2016 also identified association of the DUSP15 intronic SNP rs37466599 with autism under allelic (P=0.0018), additive (P=0.001), and dominant (P=0.007) models.

Reports Added
[Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.2017]
7/1/2016
icon
4

Increased from to 4

Description

A de novo missense variant in the DUSP15 gene that was predicted to be damaging was identified in an ASD proband in Neale et al., 2012; a second de novo missense variant in this gene that was predicted to be disease causing by MutationTaster was identified in an ASD proband of Chinese Han descent in Tian et al., 2016. An assocation study consisting of 255 children with ASD and 427 ethnically-matched healthy controls in Tian et al., 2016 also identified association of the DUSP15 intronic SNP rs37466599 with autism under allelic (P=0.0018), additive (P=0.001), and dominant (P=0.007) models.

Krishnan Probability Score

Score 0.49177981392733

Ranking 5094/25841 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 0.000219668008201

Ranking 12663/18225 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 0.64503850356797

Ranking 875/18665 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 -0.15454390083408

Ranking 14267/20870 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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