Human Gene Module / Chromosome 10 / WDFY4

WDFY4WDFY family member 4

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 11
Rare Variants / Common Variants
16 / 0
Aliases
WDFY4, C10orf64
Associated Syndromes
-
Chromosome Band
10q11.23
Associated Disorders
-
Relevance to Autism

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

Molecular Function

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to WDFY4 (11 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 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
3 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
4 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
5 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity Coe BP , et al. (2018) No -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders Suzuki T et al. (2020) Yes -
8 Support - Woodbury-Smith M et al. (2022) Yes -
9 Support - Zhou X et al. (2022) Yes -
10 Support - Wang J et al. (2023) Yes -
11 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (16)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.7414C>T p.Arg2472Trp missense_variant De novo - - 28135719 et al. (2017)
c.7001-6C>A - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.2619C>A p.Asn873Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5941C>G p.Pro1981Ala missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.7968C>T p.Cys2656%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.4040T>G p.Ile1347Ser missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.2757G>A p.Pro919%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.8519C>T p.Pro2840Leu missense_variant De novo - Simplex 27525107 Yuen RK et al. (2016)
c.1454T>A p.Met485Lys missense_variant De novo - Simplex 32530565 Suzuki T et al. (2020)
c.445G>A p.Gly149Arg missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.908C>T p.Ser303Leu missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.7328C>T p.Pro2443Leu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.5387C>A p.Ala1796Asp missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.7546C>A p.Leu2516Met missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.972-1G>T - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.4915del p.Thr1639ProfsTer6 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

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.

7/1/2020
2
icon
2

Score remained at 2

Description

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

Reports Added
[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

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

Decreased from 3 to 3

Description

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

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

Increased from to 3

Description

De novo missense variants in the WDFY4 gene have been identified in four probands with ASD (Iossifov et al., 2014; Yuen et al., 2016; Yuen et al., 2017) and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified WDFY4 as a gene with an excess of missense variants (false discovery rata < 5%, count >1); WDFY4 was similarly identified as a gene with an excess of de novo missense variants (false discovery rata < 5%, count >1) following analysis of 5,624 cases with a primary diagnosis of ASD (Coe et al., 2018).

Krishnan Probability Score

Score 0.47560107230917

Ranking 8561/25841 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
Sanders TADA Score

Score 0.94554151576874

Ranking 16511/18665 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 0.007773966940073

Ranking 8437/20870 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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