EEF1A2
Chr 20eukaryotic translation elongation factor 1 alpha 2
Also known as: DEE33, EEF1AL, EF-1-alpha-2, EF1A, EIEE33, HS1, MRD38, STN
The protein catalyzes the enzymatic delivery of aminoacyl tRNAs to the ribosome as part of the elongation factor-1 complex and is specifically expressed in brain, heart, and skeletal muscle. Loss-of-function mutations cause developmental and epileptic encephalopathy 33 and autosomal dominant intellectual developmental disorder 38 through an autosomal dominant inheritance pattern. The high intolerance to loss-of-function variants (pLI 0.996, LOEUF 0.186) reflects the protein's essential role in translation elongation during protein synthesis.
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
452 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 5 | 33 | 0 | 38 |
Likely Pathogenic | 0 | 19 | 10 | 0 | 29 |
VUS | 7 | 128 | 34 | 3 | 172 |
Likely Benign | 0 | 3 | 68 | 106 | 177 |
Benign | 0 | 1 | 12 | 6 | 19 |
Conflicting | — | 11 | |||
| Total | 7 | 156 | 157 | 115 | 446 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
EEF1A2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Italian Digital Primary Cardiovascular Prevention Study
ACTIVE NOT RECRUITINGStatin Therapy in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study
RECRUITINGMyGeneRank: A Digital Platform for Next-Generation Genetic Studies
RECRUITINGAtorvastatin for Preventing Disease Metastasis in Patients With Resected High-Risk Stage IIA, IIB, or IIIA Melanoma
ACTIVE NOT RECRUITINGMulti-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis
ACTIVE NOT RECRUITINGEffect of Breastfeeding on Lipid Profile and Cardiovascular Risk Markers in Women With Familial Hypercholesterolemia
ACTIVE NOT RECRUITINGPolygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention
ENROLLING BY INVITATIONCognitive Decline and Underlying Mechanisms in Symptomatic Intracranial Artery Stenosis Patients: A Cohort Study
RECRUITINGNPC1L1 Gene Polymorphism and the Efficacy and Safety of Hybutimibe
NOT YET RECRUITINGMRI Functional Imaging Characteristics and Fat Quantification of CT-fat-free Renal Neoplasms: Relationships With Histological Classifications and Molecular Markers
ACTIVE NOT RECRUITINGStatin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)
RECRUITINGCholesterol Lowering and Residual Risk in Diabetes, Type 1
RECRUITINGExternal Resources
Links to major genomics databases and tools