Human Gene Module / Chromosome 5 / DPYSL3

DPYSL3dihydropyrimidinase like 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
3 / 0
Aliases
DPYSL3, CRMP-4,  CRMP4,  DRP-3,  DRP3,  LCRMP,  ULIP,  ULIP-1
Associated Syndromes
-
Chromosome Band
5q32
Associated Disorders
-
Relevance to Autism

A de novo missense variant in the DPYSL3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; this variant was predicted to be possibly damaging and was present in both dbSNP and ESP. A rare de novo missense variant in DPYSL3 (p.Ser541Tyr) that was experimentally shown to result in a partial loss-of-function effect was identified in an ASD proband from the Central Ohio Registry for Autism (CORA) in Tsutiya et al., 2017. Tsutiya et al., 2017 further demonstrated that DPSYL3 knockout mice exhibited reduced social interaction and several alterations in sensory responses, with most of these changes being more severe in male mice than in females.

Molecular Function

Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration

External Links
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Human
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Mouse
Entrez Gene
SFARI Genomic Platforms
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Reports related to DPYSL3 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation Human CRMP4 mutation and disrupted Crmp4 expression in mice are associated with ASD characteristics and sexual dimorphism Tsutiya A , et al. (2017) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1952G>A p.Gly651Glu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.415G>A p.Val139Ile missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1622C>A p.Ser541Tyr missense_variant De novo - Simplex 29196732 Tsutiya A , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo missense variant in the DPYSL3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; this variant was predicted to be possibly damaging and was present in both dbSNP and ESP. A rare de novo missense variant in DPYSL3 (p.Ser541Tyr) that was experimentally shown to result in a partial loss-of-function effect was identified in an ASD proband from the Central Ohio Registry for Autism (CORA) in Tsutiya et al., 2017. Tsutiya et al., 2017 further demonstrated that DPSYL3 knockout mice exhibited reduced social interaction and several alterations in sensory responses, with most of these changes being more severe in male mice than in females.

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 DPYSL3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; this variant was predicted to be possibly damaging and was present in both dbSNP and ESP. A rare de novo missense variant in DPYSL3 (p.Ser541Tyr) that was experimentally shown to result in a partial loss-of-function effect was identified in an ASD proband from the Central Ohio Registry for Autism (CORA) in Tsutiya et al., 2017. Tsutiya et al., 2017 further demonstrated that DPSYL3 knockout mice exhibited reduced social interaction and several alterations in sensory responses, with most of these changes being more severe in male mice than in females.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo missense variant in the DPYSL3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; this variant was predicted to be possibly damaging and was present in both dbSNP and ESP. A rare de novo missense variant in DPYSL3 (p.Ser541Tyr) that was experimentally shown to result in a partial loss-of-function effect was identified in an ASD proband from the Central Ohio Registry for Autism (CORA) in Tsutiya et al., 2017. Tsutiya et al., 2017 further demonstrated that DPSYL3 knockout mice exhibited reduced social interaction and several alterations in sensory responses, with most of these changes being more severe in male mice than in females.

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

Increased from to 4

Description

A de novo missense variant in the DPYSL3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; this variant was predicted to be possibly damaging and was present in both dbSNP and ESP. A rare de novo missense variant in DPYSL3 (p.Ser541Tyr) that was experimentally shown to result in a partial loss-of-function effect was identified in an ASD proband from the Central Ohio Registry for Autism (CORA) in Tsutiya et al., 2017. Tsutiya et al., 2017 further demonstrated that DPSYL3 knockout mice exhibited reduced social interaction and several alterations in sensory responses, with most of these changes being more severe in male mice than in females.

Krishnan Probability Score

Score 0.535873660263

Ranking 1486/25841 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 0.9964831736437

Ranking 1403/18225 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 0.93479332439614

Ranking 12677/18665 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 -0.080050847348505

Ranking 11580/20870 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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