Human Gene Module / Chromosome 4 / EIF4E

EIF4Eeukaryotic translation initiation factor 4E

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 12
Rare Variants / Common Variants
4 / 3
Aliases
EIF4E, CBP,  EIF4F,  EIF4E1,  EIF4EL1,  MGC111573,  EIF4E
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
4q23
Associated Disorders
-
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... 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 - Simplex 19556253 Neves-Pereira M , et al. (2009)
c.540-10T>G - intron_variant - - Multiplex 22558107 Kelleher RJ 3rd , et al. (2012)
c.-25insC - 2KB_upstream_variant Familial Paternal Multiplex 19556253 Neves-Pereira M , et al. (2009)
c.194A>T;c.254A>T p.Lys65Met;p.Lys85Met missense_variant De novo - Simplex 27525107 Yuen RK , et al. (2016)
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
3

Suggestive Evidence

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

Score Delta: Score remained at 4

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.

7/1/2016
4
icon
4

Score remained at 4

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
Submit New Gene

Report an Error