Human Gene Module / Chromosome 4 / EIF4E

EIF4Eeukaryotic translation initiation factor 4E

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 12
Rare Variants / Common Variants
4 / 3
EAGLE Score
3.6
Limited Learn More
Aliases
EIF4E, CBP,  EIF4F,  EIF4E1,  EIF4EL1,  MGC111573,  EIF4E
Associated Syndromes
-
Chromosome Band
4q23
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Relevance to Autism

Rare variants in the EIF4E gene have been identified with autism (Neves-Pereira et al., 2009).

Molecular Function

Translation initiation factor involved in directing ribosomes to the cap structure of mRNAs

Reports related to EIF4E (12 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Tumstatin, an endothelial cell-specific inhibitor of protein synthesis Maeshima Y , et al. (2002) No -
2 Highly Cited The translational repressor Pumilio regulates presynaptic morphology and controls postsynaptic accumulation of translation factor eIF-4E Menon KP , et al. (2004) No -
3 Recent Recommendation eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans Syntichaki P , et al. (2007) No -
4 Recent Recommendation Role of the phosphoinositide 3-kinase-Akt-mammalian target of the rapamycin signaling pathway in long-term potentiation and trace fear conditioning memory in rat medial prefrontal cortex Sui L , et al. (2008) No -
5 Primary Deregulation of EIF4E: a novel mechanism for autism Neves-Pereira M , et al. (2009) Yes -
6 Support High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism Kelleher RJ 3rd , et al. (2012) Yes -
7 Recent Recommendation Exaggerated translation causes synaptic and behavioural aberrations associated with autism Santini E , et al. (2012) No -
8 Positive Association Common EIF4E variants modulate risk for autism spectrum disorders in the high-functioning range Waltes R , et al. (2014) Yes -
9 Support Genome-wide characteristics of de novo mutations in autism Yuen RK et al. (2016) Yes -
10 Highly Cited Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function Pause A , et al. (1994) No -
11 Highly Cited The mRNA 5' cap-binding protein eIF4E and control of cell growth Sonenberg N and Gingras AC (1998) No -
12 Highly Cited Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism Hara K , et al. (1998) No -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo NA Simplex 19556253 Neves-Pereira M , et al. (2009)
c.540-10T>G - intron_variant - - Multiplex 22558107 Kelleher RJ 3rd , et al. (2012)
c.194A>T p.Lys65Met missense_variant De novo NA Simplex 27525107 Yuen RK et al. (2016)
c.-25insC - 2KB_upstream_variant Familial Paternal Multiplex 19556253 Neves-Pereira M , et al. (2009)
Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.282-319C>T;c.222-319C>T;c.306-319C>T - intron_variant - - - 24818597 Waltes R , et al. (2014)
c.185+4194T>G;c.125+4194T>G;c.209+4194T>G - intron_variant - - - 24818597 Waltes R , et al. (2014)
c.186-3048A>G;c.126-3048A>G;c.210-3048A>G - intron_variant - - - 24818597 Waltes R , et al. (2014)
SFARI Gene score
2

Strong Candidate

Region of linkage and rare mutations in several families associated with promoter activity.

Score Delta: Decreased from 4 to 3

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.

10/1/2021
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

7/1/2021
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

4/1/2021
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

1/1/2021
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

10/1/2020
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

7/1/2020
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

4/1/2020
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

1/1/2020
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Region of linkage and rare mutations in several families associated with promoter activity.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

4/1/2019
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

1/1/2019
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

10/1/2018
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

10/1/2017
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

10/1/2016
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

7/1/2016
4
icon
4

Decreased from 4 to 4

Description

Region of linkage and rare mutations in several families associated with promoter activity.

10/1/2015
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

10/1/2014
4
icon
3

Decreased from 4 to 3

Description

Region of linkage and rare mutations in several families associated with promoter activity.

7/1/2014
No data
icon
4

Increased from No data to 4

Description

Region of linkage and rare mutations in several families associated with promoter activity.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Region of linkage and rare mutations in several families associated with promoter activity.

Krishnan Probability Score

Score 0.50105149707727

Ranking 2043/25841 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 0.98357334219433

Ranking 2026/18225 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 0.90900448393809

Ranking 7398/18665 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 8

Ranking 223/461 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 -0.19531061482038

Ranking 15317/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ANGEL1 angel homolog 1 (Drosophila) Human Protein Binding 23357 Q9UNK9
CYFIP1 Cytoplasmic FMR1-interacting protein 1 Mouse Protein Binding 20430 Q7TMB8
EIF4EBP2 eukaryotic translation initiation factor 4E binding protein 2 Human Protein Binding 1979 Q13542
EIF4EBP3 eukaryotic translation initiation factor 4E binding protein 3 Human Protein Binding 8637 O60516
KANK2 KN motif and ankyrin repeat domains 2 Human Protein Binding 25959 Q63ZY3
MKNK1 MAP kinase interacting serine/threonine kinase 1 Human Protein Modification 8569 Q9BUB5
park park Fruit Fly Protein Binding 40336 Q7KTX7
STUB1 STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase Human Protein Modification 10273 Q9UNE7
TDO2 tryptophan 2,3-dioxygenase Human Protein Binding 6999 P48775
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