# EIF2AK3

Source: https://onco.cc/targets/eif2ak3/  
OnCo record `eif2ak3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

EIF2AK3 (Eukaryotic translation initiation factor 2-alpha kinase 3) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. In the public catalogues the evidence so far is association rather than a proven role.

## Summary

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognises and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming.

Open Targets scores its association with cancer at 0.54 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.83, animal model 0.48, genetic association 0.08).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: eukaryotic translation initiation factor 2 alpha kinase 3; Eukaryotic translation initiation factor 2-alpha kinase 3
- Tags: cancer-genes-wave
- Symbol: EIF2AK3
- Class: kinase
- Biology: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognises and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation. EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming. The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes. In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites. In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2. Location: Endoplasmic reticulum membrane (UniProt). Locus 2p11.2 (HGNC).

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: none stated by the sources. Evidence tier "association-only" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:3255: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3255
- UniProt Q9NZJ5: https://www.uniprot.org/uniprotkb/Q9NZJ5/entry
- NCBI Gene 9451: https://www.ncbi.nlm.nih.gov/gene/9451
- Ensembl ENSG00000172071: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000172071

## Connected records

- collections: [Open Targets Platform](https://onco.cc/collections/open-targets/)

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