EEF2

Chr 19

eukaryotic translation elongation factor 2

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

NCBI Gene: 1938 ENSG00000167658 UniProt: P13639

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpinocerebellar ataxia 26

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · spinocerebellar ataxia type 26 · AD · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

108

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in EEF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

930 rare PASS variants

Rare truncating (LoF)

1 in 450

66 rare PASS variants

Rare synonymous (reference)

1 in 33

786 rare PASS variants

Rare missense and truncating variants are carried at similar rates in EEF2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 470
South Asian	~43k	1 in 89	1 in 610
Remaining (unassigned)	~30k	1 in 150	1 in 650
European (Finnish)	~27k	1 in 150	1 in 660
Admixed American	~22k	1 in 78	1 in 300
African / African American	~21k	1 in 89	1 in 190
East Asian	~20k	1 in 130	1 in 2,600
Ashkenazi Jewish	~13k	1 in 250	1 in 1,700
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 15 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 15.? see exons ↓