EEF1A2

Chr 20AD

eukaryotic translation elongation factor 1 alpha 2

Also known as: DEE33, EEF1AL, EF-1-alpha-2, EF1A, EIEE33, HS1, MRD38, STN

NCBI Gene: 1917 ENSG00000101210 UniProt: Q05639 OMIM: 602959

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This isoform (alpha 2) is expressed in brain, heart and skeletal muscle, and the other isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas. This gene may be critical in the development of ovarian cancer. [provided by RefSeq, Mar 2014]

OMIM ResearchGenerating clinical summary…

GOFmechanismADLOEUF 0.192 OMIM phenotypes

Clinical Summary— EEF1A2

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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ClinVar Variants

48 unique Pathogenic / Likely Pathogenic· 204 VUS of 665 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.19)

0≤0.351.4

Missense OE?0.23 (0.18–0.28)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 0 / 16.0Missense obs/exp: 69 / 306.2Syn Z: 0.83

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongEEF1A2-related infantile epileptic encephalopathyGOFAD

This gene — mechanism propensity

0.4587th %ile

GOF

0.4381th %ile

LOF

0.72top 10%

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.

LOFprediction above median · 1 literature citation · LOEUF 0.19

GOF1 literature citation · 85% of P/LP are missense

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

GOFRecapitulation of the EEF1A2 D252H neurodevelopmental disorder-causing missense mutation in mice reveals a toxic gain of function.1

LOFPathogenic variants appear to act via a haploinsufficiency mechanism, disrupting both the protein synthesis and integrated stress response functions of EEF1A2.2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

ClinVar Variant Classifications

665 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic34

VUS204

Likely Benign328

Benign52

Conflicting27

Pathogenic

Likely Pathogenic

204

VUS

328

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	8	6	0	14
Likely Pathogenic	1	33	0	0	34
VUS	10	167	24	3	204
Likely Benign	0	10	113	205	328
Benign	0	1	40	11	52
Conflicting	—				27
Total	11	219	183	219	659

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

61 pathogenic / likely-pathogenic (of 90) ClinVar copy-number / structural variants overlap EEF1A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

EEF1A2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

PRS-based Primary Prevention of CVD

Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

ACTIVE NOT RECRUITING

NCT06820086Phase PHASE4Mikk JÜRISSONStarted 2025-03-26

Rosuvastatin 20mg

Healthy Population

Italian Digital Primary Cardiovascular Prevention Study

ACTIVE NOT RECRUITING

NCT05339841Phase NACentro Cardiologico MonzinoStarted 2022-06-10

Mobile health application

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)

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

Primary Sclerosing CholangitisInflammatory Bowel Diseases

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

RECRUITING

NCT05912387Phase EARLY_PHASE1Stanford UniversityStarted 2023-05-31