Human Gene Module / Chromosome 6 / WASF1

WASF1WAS protein family member 1

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
2 / 5
Rare Variants / Common Variants
11 / 0
Aliases
WASF1, SCAR1,  WAVE,  WAVE1
Associated Syndromes
-
Chromosome Band
6q21
Associated Disorders
-
Relevance to Autism

Ito et al., 2018 identified five unrelated individuals with de novo truncating variants in the WASF1 gene, all of whom presented with intellectual disability, autistic features, and seizures.

Molecular Function

The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to WASF1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures Ito Y , et al. (2018) No -
2 Recent Recommendation - Srivastava S et al. (2021) Yes DD
3 Support - Shimojima Yamamoto K et al. (2021) No -
4 Support - Sanchis-Juan A et al. (2023) No -
5 Support - Yasser Al-Sarraj et al. (2024) Yes Epilepsy/seizures
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1516C>T p.Arg506Ter stop_gained De novo - - 29961568 Ito Y , et al. (2018)
c.1558C>T p.Gln520Ter stop_gained De novo - - 29961568 Ito Y , et al. (2018)
c.1516C>T p.Arg506Ter stop_gained De novo - - 34356165 Srivastava S et al. (2021)
c.481T>A p.Trp161Arg missense_variant De novo - - 34356165 Srivastava S et al. (2021)
c.483G>T p.Trp161Cys missense_variant De novo - - 34356165 Srivastava S et al. (2021)
c.514A>G p.Lys172Glu missense_variant De novo - - 34356165 Srivastava S et al. (2021)
c.1558C>T p.Gln520Ter stop_gained Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
- - copy_number_loss De novo - Multiplex (monozygotic twins) 34356165 Srivastava S et al. (2021)
c.215G>A p.Arg72His missense_variant De novo - Simplex 38572415 Yasser Al-Sarraj et al. (2024)
c.1516C>T p.Arg506Ter stop_gained De novo - Simplex 34845217 Shimojima Yamamoto K et al. (2021)
c.1482delinsGCCAGG p.Ile494MetfsTer23 frameshift_variant De novo - - 29961568 Ito Y , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Ito et al., 2018 identified five unrelated individuals with de novo truncating variants in the WASF1 gene, all of whom presented with intellectual disability, autistic features, and seizures.

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."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Ito et al., 2018 identified five unrelated individuals with de novo truncating variants in the WASF1 gene, all of whom presented with intellectual disability, autistic features, and seizures.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.56683586817855

Ranking 1200/25841 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 0.91436988704024

Ranking 3095/18225 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 0.93166687086352

Ranking 11763/18665 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 0.59100379480013

Ranking 108/20870 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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