EIF2AK2

Chr 2

eukaryotic translation initiation factor 2 alpha kinase 2

Also known as: PKR, PPP1R83, PRKR

NCBI Gene: 5610ENSG00000055332UniProt: P19525

The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses. [provided by RefSeq, Jul 2021]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukoencephalopathy, developmental delay, and episodic neurologic regression syndrome
UniProtDystonia 33

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
59
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.52
LOEUF
Multiple*
Mechanism· predicted
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GeneReview available — EIF2AK2
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.52LOEUF
pLI 0.018
Z-score 3.61
OE 0.30 (0.18–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.28Z-score
OE missense 0.79 (0.70–0.88)
222 obs / 282.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.30 (0.18–0.52)
0≤0.351.4
Missense OE?0.79 (0.70–0.88)
0≤0.61.4
Synonymous OE?1.05
0≤1.21.6
LoF obs/exp: 9 / 30.5Missense obs/exp: 222 / 282.3Syn Z: -0.37

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

EIF2AK2 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients