EEF2

Chr 19AD

eukaryotic translation elongation factor 2

Also known as: EEF-2, EF-2, EF2, SCA26

NCBI Gene: 1938ENSG00000167658UniProt: P13639

This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome. This protein is completely inactivated by EF-2 kinase phosporylation. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Spinocerebellar ataxia 26MIM #609306
AD
477
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— EEF2
⚡
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
13 Pathogenic / Likely Pathogenic· 237 VUS of 477 total submissions

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.
0.17LOEUF
pLI 1.000
Z-score 5.31
OE 0.05 (0.02–0.17)
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.
4.88Z-score
OE missense 0.42 (0.38–0.47)
235 obs / 559.8 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.0.05 (0.02–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.42 (0.38–0.47)
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.1.53
0≤1.21.6
LoF obs/exp: 2 / 36.7Missense obs/exp: 235 / 559.8Syn Z: -6.67

ClinVar Variant Classifications

477 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic5
VUS237
Likely Benign178
Benign45
Conflicting4
8
Pathogenic
5
Likely Pathogenic
237
VUS
178
Likely Benign
45
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
7
0
8
Likely Pathogenic
1
3
1
0
5
VUS
11
188
29
9
237
Likely Benign
0
0
82
96
178
Benign
0
0
34
11
45
Conflicting
—4
Total12192153116477

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

View in ClinVar →

Protein Context — Lollipop Plot

EEF2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EEF2-related developmental disorder

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Spinocerebellar ataxia 26

MIM #609306

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mechanisms of ketamine action as an antidepressant.
Zanos P et al.·Mol Psychiatry
2018Review
Diphthamide - a conserved modification of eEF2 with clinical relevance.
Schaffrath R et al.·Trends Mol Med
2024Review
Gelation of cytoplasmic expanded CAG RNA repeats suppresses global protein synthesis.
Pan Y et al.·Nat Chem Biol
2023
Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression.
Jana S et al.·Cancer Cell
2023
The role of eEF2 kinase in the rapid antidepressant actions of ketamine.
Suzuki K et al.·Adv Pharmacol
2020Review
Diagnosis of hereditary ataxias: a real-world single center experience.
Meli A et al.·J Neurol
2025
Convergent Mechanisms Underlying Rapid Antidepressant Action.
Zanos P et al.·CNS Drugs
2018Review
New insights into tumor microenvironment and HPV integrations in cervical cancer pathogenesis revealed by single-cell transcriptome data.
Zeng X et al.·Hum Mol Genet
2025
Cell Death Signaling Pathway Induced by Cholix Toxin, a Cytotoxin and eEF2 ADP-Ribosyltransferase Produced by Vibrio cholerae.
Ogura K et al.·Toxins (Basel)
2020Review
Expanding the Phenotypic Spectrum Associated with DPH5-Related Diphthamide Deficiency.
Politano D et al.·Genes (Basel)
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools