Human Gene Module / Chromosome 1 / WDR26

WDR26WD repeat domain 26

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
5 / 10
Rare Variants / Common Variants
32 / 0
Aliases
WDR26, CDW2,  GID7,  MIP2
Associated Syndromes
Skraban-Deardorff syndrome, DD
Chromosome Band
1q42.11-q42.12
Associated Disorders
DD/NDD, ID, ASD
Relevance to Autism

De novo loss-of-function or missense variants in the WDR26 gene were identified in 15 individuals, all of whom presented with developmental delay/intellectual disability, seizures, gait abnormalities, and distinctive facial features; 5/9 individuals additionally presented with autistic and/or repetitive behaviors or posturing (Skraban et al., 2017). An ASD proband from the Simons Simplex Collection had previously been identified with a novel de novo WDR26 missense variant that was predicted to be damaging (Iossifov et al., 2014).

Molecular Function

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. The protein encoded by this gene may be involved in MAPK pathways.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to WDR26 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary WDR26 Haploinsufficiency Causes a Recognizable Syndrome of Intellectual Disability, Seizures, Abnormal Gait, and Distinctive Facial Features Skraban CM , et al. (2017) No Autistic behavior, repetitive behaviors
3 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
4 Support The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders Jiao Q , et al. (2019) No DD, ID
5 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Microcephaly
6 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Support - Spataro N et al. (2023) No Autistic features
9 Support - Sanchis-Juan A et al. (2023) No -
10 Support - Erica Rosina et al. (2024) No -
Rare Variants   (32)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain De novo - - 36980980 Spataro N et al. (2023)
c.1371+1G>A - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.-142del - frameshift_variant De novo - Simplex 31674007 Wu H , et al. (2019)
c.137C>A p.Ser46Ter stop_gained De novo - - 28686853 Skraban CM , et al. (2017)
c.943C>T p.Arg315Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.983C>T p.Pro328Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.835C>T p.Arg279Ter stop_gained De novo - - 28686853 Skraban CM , et al. (2017)
c.1371+2dup - splice_site_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.1031C>T p.Pro344Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1040C>T p.Thr347Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1759G>A p.Ala587Thr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1276G>T p.Glu426Ter stop_gained De novo - - 28686853 Skraban CM , et al. (2017)
c.1284G>A p.Trp428Ter stop_gained De novo - - 28686853 Skraban CM , et al. (2017)
c.1570C>T p.Gln524Ter stop_gained De novo - - 28686853 Skraban CM , et al. (2017)
c.1101_1110+1del - frameshift_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.514T>A p.Trp172Arg missense_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.644T>C p.Leu215Pro missense_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.762T>G p.Ser254Arg missense_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.850G>A p.Asp284Asn missense_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.580G>A p.Ala194Thr missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.896G>A p.Arg299Gln missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.863-1G>A - splice_site_variant Unknown Not paternal - 36980980 Spataro N et al. (2023)
c.1130C>G p.Thr377Arg missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.725C>T p.Pro242Leu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.192_198del p.Ser65ProfsTer8 frameshift_variant De novo - - 30945278 Jiao Q , et al. (2019)
c.574dup p.Ile192AsnfsTer32 frameshift_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.1409del p.Val470GlufsTer9 frameshift_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.929A>G p.Glu310Gly missense_variant Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
c.916C>T p.Arg306Trp missense_variant Familial Maternal Simplex 33004838 Wang T et al. (2020)
c.904_905del p.Gln302AspfsTer22 frameshift_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.1161_1162del p.His389ProfsTer6 frameshift_variant De novo - - 28686853 Skraban CM , et al. (2017)
c.1217A>G p.Tyr406Cys missense_variant Familial Maternal Multiplex 38041506 Erica Rosina et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

De novo loss-of-function or missense variants in the WDR26 gene were identified in 15 individuals, all of whom presented with developmental delay/intellectual disability, seizures, gait abnormalities, and distinctive facial features; 5/9 individuals additionally presented with autistic and/or repetitive behaviors or posturing (Skraban et al., 2017). An ASD proband from the Simons Simplex Collection had previously been identified with a novel de novo WDR26 missense variant that was predicted to be damaging (Iossifov et al., 2014).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

10/1/2020
S
icon
S

Score remained at S

Description

De novo loss-of-function or missense variants in the WDR26 gene were identified in 15 individuals, all of whom presented with developmental delay/intellectual disability, seizures, gait abnormalities, and distinctive facial features; 5/9 individuals additionally presented with autistic and/or repetitive behaviors or posturing (Skraban et al., 2017). An ASD proband from the Simons Simplex Collection had previously been identified with a novel de novo WDR26 missense variant that was predicted to be damaging (Iossifov et al., 2014).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

De novo loss-of-function or missense variants in the WDR26 gene were identified in 15 individuals, all of whom presented with developmental delay/intellectual disability, seizures, gait abnormalities, and distinctive facial features; 5/9 individuals additionally presented with autistic and/or repetitive behaviors or posturing (Skraban et al., 2017). An ASD proband from the Simons Simplex Collection had previously been identified with a novel de novo WDR26 missense variant that was predicted to be damaging (Iossifov et al., 2014).

Reports Added
[Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
4/1/2019
S
icon
S

Score remained at S

Description

De novo loss-of-function or missense variants in the WDR26 gene were identified in 15 individuals, all of whom presented with developmental delay/intellectual disability, seizures, gait abnormalities, and distinctive facial features; 5/9 individuals additionally presented with autistic and/or repetitive behaviors or posturing (Skraban et al., 2017). An ASD proband from the Simons Simplex Collection had previously been identified with a novel de novo WDR26 missense variant that was predicted to be damaging (Iossifov et al., 2014).

Reports Added
[The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.2019]
Krishnan Probability Score

Score 0.49496630238446

Ranking 3308/25841 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 0.99967739101451

Ranking 852/18225 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 0.71502729123381

Ranking 1258/18665 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 0.55605813771844

Ranking 222/20870 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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