Human Gene Module / Chromosome 2 / VIL1

VIL1Villin 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
18 / 0
Aliases
VIL1, D2S1471,  VIL
Associated Syndromes
-
Chromosome Band
2q35
Associated Disorders
-
Relevance to Autism

This gene was identified in an ASD whole-exome sequencing study and subsequent TADA (transmission and de novo association) analysis as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (De Rubeis et al., 2014).

Molecular Function

This gene encodes a member of a family of calcium-regulated actin-binding proteins. This protein represents a dominant part of the brush border cytoskeleton which functions in the capping, severing, and bundling of actin filaments.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to VIL1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Macrocephaly
4 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (18)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.75+1G>C - splice_site_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.614G>A p.Arg205His missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.603G>T p.Glu201Asp missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.839T>C p.Leu280Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1390G>A p.Val464Ile missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1514G>A p.Arg505Gln missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.749A>C p.Lys250Thr splice_site_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.567+1G>A - splice_site_variant Familial Paternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.128G>A p.Gly43Asp missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1671G>A p.Trp557Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.839T>C p.Leu280Pro missense_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1388C>T p.Ala463Val missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.1858C>T p.Arg620Trp missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2051C>T p.Thr684Ile missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.2223del p.Thr742LeufsTer31 frameshift_variant Familial Maternal Simplex 31674007 Wu H , et al. (2019)
c.749A>C p.Lys250Thr splice_site_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
c.712dup p.Ala238GlyfsTer23 frameshift_variant Familial Paternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.456+1G>A - splice_site_variant Familial Maternal Multiplex (monozygotic twins) 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo missense variants that are predicted to be damaging were identified in unrelated ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified VIL1 as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760).

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two de novo missense variants that are predicted to be damaging were identified in unrelated ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified VIL1 as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760).

Reports Added
[Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Two de novo missense variants that are predicted to be damaging were identified in unrelated ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified VIL1 as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene (PMID 25363760).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2014
icon
3

Increased from to 3

Description

Two de novo missense variants that are predicted to be damaging were identified in unrelated ASD probands from the Autism Sequencing Consortium (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified VIL1 as a gene meeting high statistical significance with a 0.05

Krishnan Probability Score

Score 0.4121355073873

Ranking 22201/25841 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 1.2127822249729E-5

Ranking 14132/18225 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 0.13176470910457

Ranking 78/18665 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
Larsen Cumulative Evidence Score

Score 23

Ranking 87/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.3876799085096

Ranking 18242/20870 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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