EIF2A

Chr 3

eukaryotic translation initiation factor 2A

Also known as: CDA02, EIF-2A, MST089, MSTP004, MSTP089

NCBI Gene: 83939 ENSG00000144895 UniProt: Q9BY44

This gene encodes a eukaryotic translation initiation factor that catalyzes the formation of puromycin-sensitive 80 S preinitiation complexes and the poly(U)-directed synthesis of polyphenylalanine at low concentrations of Mg2+. This gene should not be confused with eIF2-alpha (EIF2S1, Gene ID: 1965), the alpha subunit of the eIF2 translation initiation complex. Although both of these proteins function in binding initiator tRNA to the 40 S ribosomal subunit, the encoded protein does so in a codon-dependent manner, whereas eIF2 complex requires GTP. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.88

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.09

OE 0.59 (0.41–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.10Z-score

OE missense 0.82 (0.73–0.91)

229 obs / 280.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.41–0.88)

0≤0.351.4

Missense OE?0.82 (0.73–0.91)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 18 / 30.4Missense obs/exp: 229 / 280.8Syn Z: 1.31

Background carrier burden — how many people carry a rare variant somewhere in EIF2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

667 rare PASS variants

Rare truncating (LoF)

1 in 1,100

165 rare PASS variants

Rare synonymous (reference)

1 in 480

221 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EIF2A. 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 120	1 in 1,500
South Asian	~43k	1 in 95	1 in 400
Remaining (unassigned)	~30k	1 in 80	1 in 400
European (Finnish)	~27k	1 in 280	≈ 1 in 8,200
Admixed American	~22k	1 in 85	1 in 1,100
African / African American	~21k	1 in 96	1 in 970
East Asian	~20k	1 in 180	1 in 790
Ashkenazi Jewish	~13k	1 in 790	none seen
Middle Eastern	~2,884	1 in 110	≈ 1 in 1,400

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): 13 of 14 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 14.? see exons ↓