EIF2A

Chr 3

eukaryotic translation initiation factor 2A

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

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]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.88
Clinical SummaryEIF2A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 VUS of 84 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.88LOEUF
pLI 0.000
Z-score 2.09
OE 0.59 (0.410.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.10Z-score
OE missense 0.82 (0.730.91)
229 obs / 280.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.59 (0.410.88)
00.351.4
Missense OE?0.82 (0.730.91)
00.61.4
Synonymous OE?0.83
01.21.6
LoF obs/exp: 18 / 30.4Missense obs/exp: 229 / 280.8Syn Z: 1.31

This gene — mechanism propensity

DN
0.6743th %ile
GOF
0.3392th %ile
LOF
0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

84 submitted variants in ClinVar

Classification Summary

VUS63
Likely Benign2
63
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
63
0
0
63
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0650065

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap EIF2A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

EIF2A · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →