Human Gene Module / Chromosome 19 / EIF3G

EIF3Geukaryotic translation initiation factor 3 subunit G

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
6 / 0
EAGLE Score
1.5
Limited Learn More
Aliases
EIF3G, EIF3-P42,  EIF3S4,  eIF3-delta,  eIF3-p44
Associated Syndromes
-
Chromosome Band
19p13.2
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

De novo variants in the EIF3G gene, including a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator, have been identified in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 5.02E-04 (Takata et al., 2016).

Molecular Function

The protein encoded by this gene is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis.

External Links
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SFARI Genomic Platforms
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Reports related to EIF3G (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Primary De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
3 Recent Recommendation De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia Takata A , et al. (2016) No -
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 - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.580G>C p.Glu194Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - downstream_gene_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.142C>T p.Leu48= synonymous_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.847G>A p.Ala283Thr missense_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.701G>A p.Arg234Lys missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.577A>G p.Lys193Glu missense_variant De novo - Multiplex 31981491 Satterstrom FK et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

4/1/2022
3
icon
1

Decreased from 3 to 1

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

De novo variants in the EIF3G gene, including a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator, have been identified in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 5.02E-04 (Takata et al., 2016).

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

De novo variants in the EIF3G gene, including a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator, have been identified in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 5.02E-04 (Takata et al., 2016).

Reports Added
[New Scoring Scheme]
4/1/2016
icon
4

Increased from to 4

Description

De novo variants in the EIF3G gene, including a missense variant and a synonymous variant predicted in PMID 26938441 to affect splicing regulation by altering an exonic splicing regulator, have been identified in ASD probands from the Simons Simplex Collection (O'Roak et al., 2012; Iossifov et al., 2012). Evaluation of the statistical significance of observing multiple functional de novo variants in this gene, taking into account gene length and local sequence context to determine the expected number of variants, generated a p-value of 5.02E-04 (Takata et al., 2016).

Krishnan Probability Score

Score 0.48749234229363

Ranking 6960/25841 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 0.98342249155956

Ranking 2028/18225 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 0.698449269431

Ranking 1147/18665 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 -0.29083307448232

Ranking 17074/20870 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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