EEF1A2

Chr 20

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

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 33

UniProtIntellectual developmental disorder, autosomal dominant 38

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · complex neurodevelopmental disorder · AD · ClinGen 2019

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

GOF*

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?

0.19LOEUF

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

Background carrier burden — how many people carry a rare variant somewhere in EEF1A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 810

230 rare PASS variants

Rare truncating (LoF)

1 in 22,000

14 rare PASS variants

Rare synonymous (reference)

1 in 120

303 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EEF1A2. 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 1,100	1 in 77,000
South Asian	~43k	1 in 460	1 in 7,400
Remaining (unassigned)	~30k	1 in 930	none seen
European (Finnish)	~26k	1 in 900	≈ 1 in 25,000
Admixed American	~22k	1 in 790	none seen
African / African American	~21k	1 in 1,100	≈ 1 in 21,000
East Asian	~20k	1 in 870	1 in 2,600
Ashkenazi Jewish	~13k	1 in 1,300	none seen
Middle Eastern	~2,884	≈ 1 in 720	none seen

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 7.? see exons ↓