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EEF1A2
eukaryotic translation elongation factor 1 alpha 2
EEF1A2 encodes a translation elongation factor critical for protein synthesis in the brain and muscle, with variants linked to severe neurological conditions. The EEF1A2 gene provides instructions for making a protein that helps cells build other proteins by delivering amino acids during translation.
EEF1A2 is located on the long (q) arm of chromosome 20, at band 20q13.33. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 20 in the library →Overview
EEF1A2 (eukaryotic translation elongation factor 1 alpha 2) encodes one of two closely related translation elongation factors in human cells. Whilst the related protein EEF1A1 is expressed widely throughout the body, EEF1A2 shows highly restricted expression, predominantly in brain tissue and skeletal muscle. This tissue-specific distribution reflects the particularly demanding protein synthesis requirements of neurons and muscle fibres.
The gene is located on chromosome 20 and produces a 463-amino-acid protein that plays an essential role in delivering aminoacyl-tRNA molecules to the ribosome during protein synthesis. Pathogenic variants in EEF1A2 are associated with severe neurodevelopmental conditions, particularly early-onset epilepsy and intellectual disability. The gene follows an autosomal dominant inheritance pattern, meaning a single altered copy can cause disease.
What the gene does
The EEF1A2 protein functions as a key component of the cellular machinery that translates genetic information into functional proteins. During translation elongation, this factor binds to aminoacyl-tRNA molecules and escorts them to the ribosome, where they are incorporated into growing protein chains. After delivering its cargo, the protein releases the tRNA and is recycled in a GTP-dependent manner, allowing the cycle to continue.
Beyond its canonical role in translation, research suggests EEF1A2 may participate in additional cellular processes including the organisation of the cytoskeleton and the bundling of actin filaments. The protein's particularly high expression in post-mitotic neurons - cells that no longer divide - appears essential for maintaining the substantial protein synthesis demands of mature brain tissue. In muscle cells, EEF1A2 similarly supports the production of contractile proteins and other components required for muscle function.
The tissue-restricted expression pattern of EEF1A2 means that neurons and muscle cells cannot adequately compensate using the ubiquitously expressed EEF1A1 protein, making these tissues especially vulnerable when EEF1A2 function is disrupted.
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Chromosome location
EEF1A2 is located on the long arm of chromosome 20 at position 20q13.33. This chromosomal region lies near the telomere of chromosome 20. The gene comprises multiple exons that encode the 463-amino-acid protein product.
Protein structure
The EEF1A2 protein contains a GTP-binding domain (G domain characteristic of translation factors) spanning amino acids 5-242, which mediates the nucleotide binding and hydrolysis essential for the protein's function. Within this domain, five conserved regions (G1 through G5) are positioned at amino acids 14-21, 70-74, 91-94, 153-156, and 194-196 respectively. These G-box motifs form the structural framework for GTP binding and the conformational changes that occur during the GTP hydrolysis cycle.
The C-terminal portion of the protein includes a disordered region spanning amino acids 444-463. Such intrinsically disordered regions often mediate protein-protein interactions and may contribute to the additional non-translational functions attributed to EEF1A2, including cytoskeletal organisation.
Key variants
Pathogenic variants in EEF1A2 typically arise de novo, meaning they occur as new mutations rather than being inherited from parents. The majority of disease-causing variants are missense changes that alter single amino acids within the protein sequence, particularly affecting the GTP-binding domain, though other variant types including nonsense changes and deletions have been reported. These alterations disrupt the protein's ability to cycle properly between GTP-bound and GDP-bound states, impairing its role in translation elongation.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1150G>C | p.Gly384Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Developmental and epileptic encephalopathy, 33 |
c.1267C>T | p.Arg423Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Developmental and epileptic encephalopathy, 33 |
c.1295C>T | p.Thr432Met | Pathogenic/Likely pathogenic | ★★☆☆ | Intellectual disability, autosomal dominant 38 |
c.205C>T | p.Arg69Cys | Pathogenic | ★★☆☆ | Developmental and epileptic encephalopathy, 33 |
c.208G>A | p.Gly70Ser | Pathogenic | ★★☆☆ | Intellectual disability, autosomal dominant 38 |
c.271G>A | p.Asp91Asn | Pathogenic | ★★☆☆ | Intellectual disability, autosomal dominant 38 |
c.289G>A | p.Asp97Asn | Pathogenic/Likely pathogenic | ★★☆☆ | EEF1A2-related disorder |
c.364G>A | p.Glu122Lys | Pathogenic/Likely pathogenic | ★★☆☆ | EEF1A2-related disorder |
c.370G>A | p.Glu124Lys | Pathogenic/Likely pathogenic | ★★☆☆ | EEF1A2-related disorder |
c.754G>A | p.Asp252Asn | Pathogenic/Likely pathogenic | ★★☆☆ | EEF1A2-related disorder |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in EEF1A2 are associated with a spectrum of severe neurodevelopmental disorders characterised by early-onset epilepsy and intellectual disability. Affected individuals typically present in infancy or early childhood with seizures that may be difficult to control with standard anti-epileptic medications. Developmental delay is usually evident from the first year of life, with most individuals experiencing significant intellectual disability.
Additional features may include hypotonia (reduced muscle tone), movement disorders, and structural brain abnormalities visible on neuroimaging. The severity of symptoms can vary between individuals, even among those carrying variants affecting the same amino acid position, suggesting that additional genetic or environmental factors may influence disease presentation.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic EEF1A2 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
EEF1A2 is included on several NHS England Genomic Medicine Service panels. The gene holds green classification status on the DDG2P (Developmental Disorders Genotype-Phenotype Database) panel, indicating definitive evidence for its role in developmental conditions. It is also listed on the Early Onset or Syndromic Epilepsy panel and the Intellectual Disability panel, both with green status, reflecting its established clinical relevance for these presentations in the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
There are currently no evidence-based lifestyle modifications specific to EEF1A2 variants.
Supplement considerations
There are currently no evidence-based dietary supplements specific to EEF1A2 variants.
Frequently asked questions
Why does EEF1A2 primarily affect the brain despite being expressed in muscle too?
Whilst EEF1A2 is expressed in both brain and muscle tissue, the neurological features tend to dominate the clinical picture because neurons have particularly high protein synthesis demands and limited regenerative capacity. Muscle symptoms, when present, are typically milder than the neurological manifestations.
Can EEF1A2 variants be inherited from parents?
Most pathogenic EEF1A2 variants occur de novo, meaning they arise as new mutations in the affected individual rather than being passed down from parents. However, if a parent carries a pathogenic variant, there is a 50% chance of passing it to each child, following an autosomal dominant pattern.
Are there treatments available for EEF1A2-related conditions?
Treatment is currently focused on managing symptoms, particularly controlling seizures with anti-epileptic medications and providing supportive therapies such as physiotherapy and speech therapy. There are no gene-specific therapies available at present, though research into the underlying mechanisms continues.