Human Gene Module / Chromosome 11 / GAS2

GAS2Growth arrest-specific 2

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 1
Rare Variants / Common Variants
0 / 2
Aliases
GAS2, MGC32610
Associated Syndromes
-
Genetic Category
Genetic Association
Chromosome Band
11p14.3
Associated Disorders
-
Relevance to Autism

In an association study (Weiss et al., 2009), TDT of the initial scan identified two SNPs in the GAS2 gene (rs12293188 and rs16910194) that showed association with ASD in the discovery stage (P=1.2E-05 and 4.2E-05, respectively); combination of case-control association analysis with TDT data resulted in P values of 1.1E-06 and 3.7E-06, respectively. However, neither SNP showed association in the replication stage. Meta-analysis of the combined cohorts yielded P-values of 3.0E-03 and 2.8E-04 for the two SNPs in the GAS2 gene.

Molecular Function

The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity.

Reports related to GAS2 (1 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A genome-wide linkage and association scan reveals novel loci for autism. Weiss LA , et al. (2009) Yes -
Rare Variants  

No rare variants reported.

Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.724-4432G>A - intron_variant - - - 19812673 Weiss LA , et al. (2009)
c.724-13970G>A - intron_variant - - - 19812673 Weiss LA , et al. (2009)
SFARI Gene score
3

Suggestive Evidence

In an association study involving cases and controls from AGRE and other sources (Weiss et al., 2009), TDT of the initial scan identified two SNPs in the GAS2 gene (rs12293188 and rs16910194) that showed association with ASD in the discovery stage (P=1.2E-05 and 4.2E-05, respectively); combination of case-control association analysis with TDT data resulted in P values of 1.1E-06 and 3.7E-06, respectively. However, neither SNP showed association in the replication stage. Meta-analysis of the combined cohorts yielded P-values of 3.0E-03 and 2.8E-04 for the two SNPs in the GAS2 gene.

Score Delta: Decreased from 4 to 3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

In an association study involving cases and controls from AGRE and other sources (Weiss et al., 2009), TDT of the initial scan identified two SNPs in the GAS2 gene (rs12293188 and rs16910194) that showed association with ASD in the discovery stage (P=1.2E-05 and 4.2E-05, respectively); combination of case-control association analysis with TDT data resulted in P values of 1.1E-06 and 3.7E-06, respectively. However, neither SNP showed association in the replication stage. Meta-analysis of the combined cohorts yielded P-values of 3.0E-03 and 2.8E-04 for the two SNPs in the GAS2 gene.

Reports Added
[New Scoring Scheme]
7/1/2015
icon
4

Increased from to 4

Description

In an association study involving cases and controls from AGRE and other sources (Weiss et al., 2009), TDT of the initial scan identified two SNPs in the GAS2 gene (rs12293188 and rs16910194) that showed association with ASD in the discovery stage (P=1.2E-05 and 4.2E-05, respectively); combination of case-control association analysis with TDT data resulted in P values of 1.1E-06 and 3.7E-06, respectively. However, neither SNP showed association in the replication stage. Meta-analysis of the combined cohorts yielded P-values of 3.0E-03 and 2.8E-04 for the two SNPs in the GAS2 gene.

Krishnan Probability Score

Score 0.48988431099725

Ranking 6337/25841 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.
ExAC Score

Score 0.026289765504636

Ranking 9162/18225 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
Sanders TADA Score

Score 0.93491671570401

Ranking 12715/18665 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).
Larsen Cumulative Evidence Score

Score 2

Ranking 386/461 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.
Zhang D Score

Score -0.54187178255382

Ranking 19566/20870 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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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