{"entity":{"id":"eif2ak3","kind":"target","name":"EIF2AK3","aka":["eukaryotic translation initiation factor 2 alpha kinase 3","Eukaryotic translation initiation factor 2-alpha kinase 3"],"tldr":"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.\n\nOpen 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).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:3255","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3255"},{"label":"UniProt Q9NZJ5","url":"https://www.uniprot.org/uniprotkb/Q9NZJ5/entry"},{"label":"NCBI Gene 9451","url":"https://www.ncbi.nlm.nih.gov/gene/9451"},{"label":"Ensembl ENSG00000172071","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000172071"}],"tags":["cancer-genes-wave"],"related":["open-targets"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"EIF2AK3","role":[],"evidenceTier":"association-only","sources":[{"label":"HGNC HGNC:3255","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3255","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9NZJ5","url":"https://www.uniprot.org/uniprotkb/Q9NZJ5/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000172071","url":"https://platform.opentargets.org/target/ENSG00000172071/associations","note":"association with cancer (MONDO_0004992) 0.54;  (GraphQL API, CC0)"}],"hgnc":"HGNC:3255","ensembl":"ENSG00000172071","uniprot":"Q9NZJ5","entrez":"9451","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).","whereFound":[],"targetClass":"kinase","prevalence":[]},"route":"/targets/eif2ak3/","neighbours":{"collection":[{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}]}}