Human Gene Module / Chromosome 3 / DVL3

DVL3Dishevelled segment polarity protein 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
4 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
3q27.1
Associated Disorders
-
Relevance to Autism

A de novo frameshift variant in DVL3 was observed in an ASD proband from the Simons Simplex Collection (Dong et al., 2014). More recently, a Dvl1/Dvl3+/ mouse model was shown to display adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation, phenotypes which could be rescued by pharmacological activation of the canonical Wnt pathway (Belinson et al., 2016).

Molecular Function

This gene is a member of a multi-gene family which shares strong similarity with the Drosophila dishevelled gene, dsh. The Drosophila dishevelled gene encodes a cytoplasmic phosphoprotein that regulates cell proliferation.

External Links
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Human
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Mouse
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DVL3 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder Dong S , et al. (2014) Yes -
2 Recent Recommendation Prenatal ?-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors Belinson H , et al. (2016) No -
3 Recent Recommendation ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size Kadir R , et al. (2016) No -
4 Support - Woodbury-Smith M et al. (2022) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Karthika Ajit Valaparambil et al. () Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1709G>A p.Ser570Asn missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.949C>T p.Arg317Trp missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.655C>T p.Arg219Trp missense_variant Unknown - - 37943464 Karthika Ajit Valaparambil et al. ()
c.1616_1617insT p.Gln539HisfsTer43 frameshift_variant De novo - Simplex 25284784 Dong S , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo frameshift variant in DVL3 was observed in an ASD proband from the Simons Simplex Collection (Dong et al., 2014). More recently, a Dvl1/Dvl3+/ mouse model was shown to display adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation, phenotypes which could be rescued by pharmacological activation of the canonical Wnt pathway (Belinson et al., 2016).

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 frameshift variant in DVL3 was observed in an ASD proband from the Simons Simplex Collection (Dong et al., 2014). More recently, a Dvl1/Dvl3+/ mouse model was shown to display adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation, phenotypes which could be rescued by pharmacological activation of the canonical Wnt pathway (Belinson et al., 2016).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo frameshift variant in DVL3 was observed in an ASD proband from the Simons Simplex Collection (Dong et al., 2014). More recently, a Dvl1/Dvl3+/ mouse model was shown to display adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation, phenotypes which could be rescued by pharmacological activation of the canonical Wnt pathway (Belinson et al., 2016).

Reports Added
[New Scoring Scheme]
4/1/2016
4
icon
4

Decreased from 4 to 4

Description

A de novo frameshift variant in DVL3 was observed in an ASD proband from the Simons Simplex Collection (Dong et al., 2014). More recently, a Dvl1?/?Dvl3+/? mouse model was shown to display adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation, phenotypes which could be rescued by pharmacological activation of the canonical Wnt pathway (Belinson et al., 2016).

Reports Added
[De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.2014] [Prenatal -catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors.2016] [ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.2016]
1/1/2016
icon
4

Increased from to 4

Description

A de novo frameshift variant in DVL3 was observed in an ASD proband from the Simons Simplex Collection (Dong et al., 2014). More recently, a Dvl1?/?Dvl3+/? mouse model was shown to display adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation, phenotypes which could be rescued by pharmacological activation of the canonical Wnt pathway (Belinson et al., 2016).

Krishnan Probability Score

Score 0.49269889236018

Ranking 4438/25841 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 0.99540294234556

Ranking 1498/18225 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 0.33198768292434

Ranking 206/18665 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 -0.26027852364304

Ranking 16560/20870 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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