Human Gene Module / Chromosome 20 / EEF1A2

EEF1A2Eukaryotic translation elongation factor 1 alpha 2

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 23
Rare Variants / Common Variants
56 / 0
Aliases
EEF1A2, EEF1AL,  EF-1-alpha-2,  EF1A,  HS1,  STN,  STNL
Associated Syndromes
Atypical Rett syndrome
Chromosome Band
20q13.33
Associated Disorders
ASD
Relevance to Autism

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

Molecular Function

This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to EEF1A2 (23 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Diagnostic exome sequencing in persons with severe intellectual disability de Ligt J , et al. (2012) No Autistic features
2 Support Exome sequencing reveals new causal mutations in children with epileptic encephalopathies Veeramah KR , et al. (2013) No -
3 Primary De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy Nakajima J , et al. (2014) No Autistic features
4 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
5 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
6 Support Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability Lam WW , et al. (2016) No -
7 Support Mutations in elongation factor EF-1 alpha affect the frequency of frameshifting and amino acid misincorporation in Saccharomyces cerevisiae Sandbaken MG and Culbertson MR (1988) No -
8 Support Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants Lecoquierre F , et al. (2019) No -
9 Support Whole exome sequencing reveals a de novo missense variant in EEF1A2 in a Rett syndrome-like patient Kaur S , et al. (2020) No Stereotypy
10 Support Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy Carvill GL et al. (2020) No Stereotypy, autistic features
11 Support The diagnostic yield of intellectual disability: combined whole genome low-coverage sequencing and medical exome sequencing Wang J et al. (2020) No -
12 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
13 Support - Hiraide T et al. (2021) No -
14 Support - Zou D et al. (2021) No -
15 Support - Mitani T et al. (2021) No -
16 Support - Chen Y et al. (2021) No -
17 Support - Zhou X et al. (2022) Yes -
18 Support - et al. () No ASD
19 Support - et al. () Yes -
20 Support - et al. () No ASD
21 Support - et al. () No DD
22 Support - et al. () No ASD, ADHD
23 Support - et al. () No -
Rare Variants   (56)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.71C>T p.Thr24Met missense_variant De novo - - 38355961 et al. ()
c.208G>A p.Gly70Ser missense_variant De novo - - 38355961 et al. ()
c.271G>A p.Asp91Asn missense_variant De novo - - 38355961 et al. ()
c.287G>A p.Arg96His missense_variant De novo - - 38355961 et al. ()
c.289G>A p.Asp97Asn missense_variant De novo - - 38355961 et al. ()
c.479C>T p.Pro160Leu missense_variant Unknown - - 38003033 et al. ()
c.311C>G p.Thr104Arg missense_variant De novo - - 38355961 et al. ()
c.364G>A p.Glu122Lys missense_variant De novo - - 38355961 et al. ()
c.370G>A p.Glu124Lys missense_variant De novo - - 38355961 et al. ()
c.754G>C p.Asp252His missense_variant De novo - - 38355961 et al. ()
c.889G>A p.Glu297Lys missense_variant De novo - - 38355961 et al. ()
c.610C>T p.Pro204Ser missense_variant Unknown - - 38438125 et al. ()
c.1084G>A p.Asp362Asn missense_variant De novo - - 38355961 et al. ()
c.1141C>T p.Arg381Trp missense_variant De novo - - 38355961 et al. ()
c.1259C>T p.Pro420Leu missense_variant De novo - - 38355961 et al. ()
c.1295C>T p.Thr432Met missense_variant De novo - - 38355961 et al. ()
c.1309G>T p.Val437Phe missense_variant De novo - - 38355961 et al. ()
c.364G>A p.Glu122Lys missense_variant De novo - Simplex 38328757 et al. ()
c.286C>T p.Arg96Cys missense_variant Familial Paternal - 38355961 et al. ()
c.364G>A p.Glu122Lys missense_variant Unknown - - 34145886 Zou D et al. (2021)
c.208G>A p.Gly70Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1066G>A p.Gly356Ser missense_variant Familial Maternal - 38355961 et al. ()
c.796C>T p.Arg266Trp missense_variant De novo - - 32429945 Wang J et al. (2020)
c.370G>A p.Glu124Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.913G>A p.Gly305Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.208G>A p.Gly70Ser missense_variant De novo - - 27441201 Lam WW , et al. (2016)
c.211A>C p.Ile71Leu missense_variant De novo - - 27441201 Lam WW , et al. (2016)
c.271G>A p.Asp91Asn missense_variant De novo - - 27441201 Lam WW , et al. (2016)
c.292T>C p.Phe98Leu missense_variant De novo - - 27441201 Lam WW , et al. (2016)
c.271G>A p.Asp91Asn missense_variant De novo - - 31893083 Kaur S , et al. (2020)
c.1314C>G p.Ile438Met missense_variant De novo - - 33004838 Wang T et al. (2020)
c.364G>A p.Glu122Lys missense_variant De novo - - 27441201 Lam WW , et al. (2016)
c.370G>A p.Glu124Lys missense_variant De novo - - 27441201 Lam WW , et al. (2016)
c.363C>T p.Gly121%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1267C>T p.Arg423Cys missense_variant De novo - - 27441201 Lam WW , et al. (2016)
c.49G>C p.Asp17His missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.208G>A p.Gly70Ser missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.271G>A p.Asp91Asn missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.293T>G p.Phe98Cys missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.364G>A p.Glu122Lys missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.374C>A p.Ala125Glu missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.796C>T p.Arg266Trp missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.1150G>C p.Gly384Arg missense_variant De novo - - 32196822 Carvill GL et al. (2020)
c.26A>C p.Asn9Thr missense_variant De novo - Simplex 34582790 Mitani T et al. (2021)
c.364G>A p.Glu122Lys missense_variant De novo - Simplex 35873028 Chen Y et al. (2021)
c.364G>A p.Glu122Lys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.370G>A p.Glu124Lys missense_variant De novo - - 31036916 Lecoquierre F , et al. (2019)
c.271G>A p.Asp91Asn missense_variant De novo - Simplex 33644862 Hiraide T et al. (2021)
c.208G>A p.Gly70Ser missense_variant De novo - Simplex 23033978 de Ligt J , et al. (2012)
c.435G>A p.Val145%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1145G>A p.Arg382His missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.364G>A p.Glu122Lys missense_variant De novo - Simplex 24697219 Nakajima J , et al. (2014)
c.754G>C p.Asp252His missense_variant De novo - Simplex 24697219 Nakajima J , et al. (2014)
c.1295C>T p.Thr432Met missense_variant Familial Maternal - 32196822 Carvill GL et al. (2020)
c.364G>A p.Glu122Lys missense_variant Unknown Not paternal - 32196822 Carvill GL et al. (2020)
c.271G>A p.Asp91Asn missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

1/1/2021
S
icon
S

Score remained at S

Description

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

Reports Added
[Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing2021]
10/1/2020
S
icon
S

Score remained at S

Description

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
4/1/2020
S
icon
S

Score remained at S

Description

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

Reports Added
[Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy2020] [The diagnostic yield of intellectual disability: combined whole genome low-coverage sequencing and medical exome sequencing2020]
1/1/2020
S
icon
S

Score remained at S

Description

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

Reports Added
[Whole exome sequencing reveals a de novo missense variant in EEF1A2 in a Rett syndrome-like patient.2020]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

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

Score remained at S

Description

Heterozygous variants in the EEF1A2 gene are associated with a form of early infantile epileptic encephalopathy (EIEE33; OMIM 616409) and a form of autosomal dominant intellectual disability (MRD38; OMIM 616393), a less severe disorder with overlapping features. De Ligt et al., 2012 and Nakajima et al., 2014 identifed de novo missense variants in the EEF1A2 gene in three unrelated patients presenting with intellectual disability, epilepsy, and autistic features. Additional de novo missense variants in this gene were identified in patients presenting with intellectual disability and epilepsy in Lam et al., 2016. A novel de novo missense variant in this gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; however, this variant was reportedly predicted to be benign in Sanders et al., 2015.

Reports Added
[Variantrecurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense v...2019]
Krishnan Probability Score

Score 0.49723556980358

Ranking 2427/25841 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 0.96413145424868

Ranking 2465/18225 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 0.93364690002733

Ranking 12331/18665 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 0.33432482699127

Ranking 2223/20870 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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