Human Gene Module / Chromosome 9 / WDR5

WDR5WD repeat domain 5

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
1 / 3
Rare Variants / Common Variants
9 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
9q34.2
Associated Disorders
-
Relevance to Autism

Snijders Blok et al., 2022 described 11 unrelated individuals with six different rare de novo germline missense variants in the WDR5 gene who presented with a neurodevelopmental syndrome characterized by speech/language delay, intellectual disability, epilepsy, autism spectrum disorder or autistic features, abnormal growth parameters, and overlapping facial features, including a bulbous nasal tip, low-set, posteriorly rotated, and/or dysplastic ears, ptosis, and thin upper lip vermillion; additional three-dimensional protein structure analysis indicated that all of the residues affected by these variants were clustered on the surface of one side of the WDR5 protein. Eising et al., 2019 had previously reported a de novo missense variant in the WDR5 gene in a proband with childhood apraxia of speech.

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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
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Reports related to WDR5 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Eising E et al. (2019) No -
2 Primary - Snijders Blok L et al. (2022) No ASD, ADHD
3 Support - Wang J et al. (2023) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.742-2del - splice_site_variant De novo - - 36408368 Snijders Blok L et al. (2022)
c.671C>A p.Pro224Gln missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.623C>T p.Thr208Met missense_variant De novo - Simplex 29463886 Eising E et al. (2019)
c.505C>G p.Ala169Pro missense_variant De novo - - 36408368 Snijders Blok L et al. (2022)
c.586C>T p.Arg196Cys missense_variant De novo - - 36408368 Snijders Blok L et al. (2022)
c.602C>T p.Ala201Val missense_variant De novo - - 36408368 Snijders Blok L et al. (2022)
c.623C>T p.Thr208Met missense_variant De novo - - 36408368 Snijders Blok L et al. (2022)
c.637G>A p.Asp213Asn missense_variant De novo - - 36408368 Snijders Blok L et al. (2022)
c.734A>G p.Lys245Arg missense_variant De novo - - 36408368 Snijders Blok L et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

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."

Krishnan Probability Score

Score 0.32764002797211

Ranking 25218/25841 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 0.99870216011753

Ranking 1134/18225 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 0.92305264436774

Ranking 9698/18665 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 0.33442383807336

Ranking 2220/20870 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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