EEF2

Chr 19AD

eukaryotic translation elongation factor 2

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

NCBI Gene: 1938 ENSG00000167658 UniProt: P13639 OMIM: 130610

This protein catalyzes the GTP-dependent ribosomal translocation step during translation elongation, moving tRNA molecules and mRNA through the ribosome during protein synthesis. Mutations cause spinocerebellar ataxia 26, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.17), reflecting the essential nature of this translation factor.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.171 OMIM phenotype

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

6 unique Pathogenic / Likely Pathogenic· 251 VUS of 577 total submissions

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?

0.17LOEUF

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?

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?

LoF OE?0.05 (0.02–0.17)

0≤0.351.4

Missense OE?0.42 (0.38–0.47)

0≤0.61.4

Synonymous OE?1.53

0≤1.21.6

LoF obs/exp: 2 / 36.7Missense obs/exp: 235 / 559.8Syn Z: -6.67

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedEEF2-related developmental disorderLOFAD

This gene — mechanism propensity

0.4190th %ile

GOF

0.4973th %ile

LOF

0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 33% of P/LP variants are LoF · LOEUF 0.17

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

577 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic4

VUS251

Likely Benign212

Benign73

Conflicting9

Pathogenic

Likely Pathogenic

251

VUS

212

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	2	2	0	0	4
VUS	13	206	22	10	251
Likely Benign	0	1	85	126	212
Benign	0	0	36	37	73
Conflicting	—				9
Total	15	211	143	173	551

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap EEF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →