EEF1A2

Chr 20AD

eukaryotic translation elongation factor 1 alpha 2

NCBI Gene: 1917ENSG00000101210UniProt: Q05639

Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (By similarity). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (By similarity)

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 33MIM #616409
AD
Intellectual developmental disorder, autosomal dominant 38MIM #616393
AD
544
ClinVar variants
82
Pathogenic / LP
1.00
pLI score· haploinsufficient
12
Active trials
Clinical Summary— EEF1A2
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
82 Pathogenic / Likely Pathogenic· 159 VUS of 544 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 0.996
Z-score 3.71
OE 0.00 (0.00–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.82Z-score
OE missense 0.23 (0.18–0.28)
69 obs / 306.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.23 (0.18–0.28)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 0 / 16.0Missense obs/exp: 69 / 306.2Syn Z: 0.83

ClinVar Variant Classifications

544 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic33
VUS159
Likely Benign235
Benign48
Conflicting20
49
Pathogenic
33
Likely Pathogenic
159
VUS
235
Likely Benign
48
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
6
43
0
49
Likely Pathogenic
0
23
10
0
33
VUS
3
109
45
2
159
Likely Benign
0
6
85
144
235
Benign
0
1
37
10
48
Conflicting
—20
Total3145220156544

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.

Gene2Phenotype Curations

EEF1A2-related infantile epileptic encephalopathy

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 33

MIM #616409

Molecular basis of disorder known

Autosomal dominant

Intellectual developmental disorder, autosomal dominant 38

MIM #616393

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expansion of the neurodevelopmental phenotype of individuals with EEF1A2 variants and genotype-phenotype study.
Paulet A et al.·Eur J Hum Genet
2024
Hypoxia-induced circ-CDYL-EEF1A2 transcriptional complex drives lung metastasis of cancer stem cells from hepatocellular carcinoma.
Kong R et al.·Cancer Lett
2023
Mild epileptic phenotype associates with de novo eef1a2 mutation: Case report and review.
De Rinaldis M et al.·Brain Dev
2020Review
Analysis of the Expression and Subcellular Distribution of eEF1A1 and eEF1A2 mRNAs during Neurodevelopment.
Wefers Z et al.·Cells
2022
Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis.
Kashyap VK et al.·Cells
2024Review
eEF1A2 and neuronal degeneration.
Abbott CM et al.·Biochem Soc Trans
2009
Analysis of eEF1A2 gene expression and copy number in cervical carcinoma.
Zheng W et al.·Medicine (Baltimore)
2023
Ac4C modification of lncRNA SIMALR promotes nasopharyngeal carcinoma progression through activating eEF1A2 to facilitate ITGB4/ITGA6 translation.
Gong S et al.·Oncogene
2024
EEF1A2 pathogenic variant presenting in an infant with failure to thrive and frequent apneas requiring respiratory support.
Vogt LM et al.·Am J Med Genet A
2022Case report
RNA-Binding Protein DHX9 Enhances Radioresistance in Metastatic Hepatocellular Carcinoma by Activation of the PI3K/Akt Pathway Through Enhanced EEF1A2 mRNA Stability.
Wang H et al.·J Biochem Mol Toxicol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cardiovascular Diseases

Personalised Hyperlipidaemia Therapies Guided by Pharmacogenomics

NOT YET RECRUITING
NCT06217523Phase NANational University of SingaporeStarted 2024-04
Pharmacogenomics-directed Hyperlipidaemia Management
Type 1 Diabetes

Cholesterol Lowering and Residual Risk in Diabetes, Type 1

RECRUITING
NCT05641753Phase PHASE4NYU Langone HealthStarted 2022-12-06
Evolocumab CartridgeAtorvastatin Calcium TabletsEzetimibe Tablets
Hypercholesterolemia, FamilialHypercholesterolemia, Familial, 1Hypercholesterolemia, Familial, 2

Genetic Testing and Motivational Counseling for FH

ACTIVE NOT RECRUITING
NCT04656028Phase NANational Medical Research Center for Therapy and Preventive MedicineStarted 2020-06-15
Genetic TestingMotivational CounselingLipid analysis
Heart Diseases

MyGeneRank: A Digital Platform for Next-Generation Genetic Studies

RECRUITING
NCT03277365Phase NAScripps Translational Science InstituteStarted 2017-09-26
Receive genetic risk information
Cirrhosis

Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis

ACTIVE NOT RECRUITING
NCT03654053Phase PHASE3VA Office of Research and DevelopmentStarted 2020-10-02
Placebo Oral TabletSimvastatin 40mg
Kidney Neoplasms

MRI Functional Imaging Characteristics and Fat Quantification of CT-fat-free Renal Neoplasms: Relationships With Histological Classifications and Molecular Markers

ACTIVE NOT RECRUITING
NCT06126159Phase NAChang Gung Memorial HospitalStarted 2019-02-11
multiparametric and fat-detection magnetic resonance imaging (MRI)
Preeclampsia (PE)Intrauterine Growth Restriction (IUGR)Placental Insufficiency

Statin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)

RECRUITING
NCT07098975Phase PHASE2Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauStarted 2026-01-14
Pravastatin 40 mgPlacebo
Pathologic Stage IIIA Cutaneous Melanoma AJCC v8Pathologic Stage IIA Cutaneous Melanoma AJCC v8Pathologic Stage IIB Cutaneous Melanoma AJCC v8

Atorvastatin for Preventing Disease Metastasis in Patients With Resected High-Risk Stage IIA, IIB, or IIIA Melanoma

RECRUITING
NCT06157099Phase PHASE2OHSU Knight Cancer InstituteStarted 2024-09-01
AtorvastatinPlacebo AdministrationComputed Tomography
Intracranial AtherosclerosisCognitive ImpairmentCerebrovascular Event

Cognitive Decline and Underlying Mechanisms in Symptomatic Intracranial Artery Stenosis Patients: A Cohort Study

RECRUITING
NCT06336174Anhui Medical UniversityStarted 2022-11-01
Aspirin Tablet, Clopidogrel Bisulfate Tablets and AtorvastatinEndovascular therapy,Aspirin Tablet, Clopidogrel Bisulfate Tablets and Atorvastatin
Gene PolymorphismASCVD

NPC1L1 Gene Polymorphism and the Efficacy and Safety of Hybutimibe

NOT YET RECRUITING
NCT06641661Qianfoshan HospitalStarted 2024-11-01
Hybutimibe 10mg QD
PRS-based Primary Prevention of CVD

Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

ENROLLING BY INVITATION
NCT06820086Phase PHASE4Mikk JÜRISSONStarted 2025-04
Rosuvastatin 20mg
Primary Sclerosing CholangitisInflammatory Bowel Diseases

Statin Therapy in Primary Sclerosing Cholangitis (PSC): a Multi-omics Study

RECRUITING
NCT05912387Phase EARLY_PHASE1Stanford UniversityStarted 2023-05-31
Rosuvastatin

External Resources

Links to major genomics databases and tools