Human Gene Module / Chromosome 4 / G3BP2

G3BP2G3BP stress granule assembly factor 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
9 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
4q21.1
Associated Disorders
-
Relevance to Autism

Two de novo missense variants in the G3BP2 gene have been identified in ASD probands (a p.Leu209Pro missense variant in an ASD proband from the Simons Simplex Collection, and a p.Arg13Trp missense variant in the ASD proband from the Autism Sequencing Consortium) (Iossifov et al., 2014; Satterstrom et al., 2020), while a de novo splice-site variant in this gene was identified in an ASD proband from the MSSNG cohort (Yuen et al., 2017). Enrichment analysis for de novo protein-altering variants in 40,853 probands with neurodevelopmental disorders, including 9,228 individuals with a primary diagnosis of ASD, in Jia et al., 2022 demonstrated that G3BP2 showed an excess of de novo missense variants with a false discovery rate (FDR) less than or equal to 0.01; subsequent functional analysis of G3BP2 missense variants used in this analysis found that three missense variants, including the ASD-associated p.Leu209Pro and p.Arg13Trp missense variants, resulted in significantly fewer stress granule formations under stress conditions compared with wild-type in transfected G3BP2 KO HeLa cells.

Molecular Function

Enables RNA binding activity. Involved in positive regulation of stress granule assembly and protein homooligomerization. Located in cytoplasmic stress granule and cytosol.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to G3BP2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
3 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
4 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
5 Support - Kaplanis J et al. (2020) No -
6 Recent Recommendation - Jia X et al. (2022) Yes -
7 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.451G>A p.Asp151Asn missense_variant De novo - - 28135719 et al. (2017)
c.1222A>G p.Lys408Glu missense_variant De novo - - 28135719 et al. (2017)
c.472G>A p.Glu158Lys missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.1197A>C p.Glu399Asp missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.1312C>T p.Arg438Cys missense_variant De novo - - 33057194 Kaplanis J et al. (2020)
c.178-2A>G - splice_site_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.37C>T p.Arg13Trp missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.1238G>C p.Arg413Thr missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.626T>C p.Leu209Pro missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

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.

1/1/2023
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2

Increased from to 2

Krishnan Probability Score

Score 0.57841117593766

Ranking 608/25841 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 0.98314541730523

Ranking 2040/18225 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 0.92766683128686

Ranking 10726/18665 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 0.41593175101081

Ranking 1276/20870 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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