{"entity":{"id":"irak1","kind":"target","name":"IRAK1","aka":["interleukin 1 receptor associated kinase 1","Interleukin-1 receptor-associated kinase 1","pelle"],"tldr":"IRAK1 (Interleukin-1 receptor-associated kinase 1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target and a tumour suppressor, and an approved or late-stage drug is recorded against it. Tied to Myeloproliferative neoplasms and Multiple myeloma.","summary":"Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signalling pathways. Is rapidly recruited by MYD88 to the receptor-signalling complex upon TLR activation.\n\nOpen Targets scores its association with cancer at 0.66 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.00, somatic mutation 0.61, clinical 0.91). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Plasma Cell Myeloma. In OnCo, 1 product record names it (Pacritinib).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6112","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6112"},{"label":"UniProt P51617","url":"https://www.uniprot.org/uniprotkb/P51617/entry"},{"label":"NCBI Gene 3654","url":"https://www.ncbi.nlm.nih.gov/gene/3654"},{"label":"Ensembl ENSG00000184216","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000184216"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["myeloproliferative-neoplasms","multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["pacritinib"],"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: Open Targets known-drug datatype score 0.91; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier \"approved-drug\" 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":"IRAK1","role":["drug-target","tumour-suppressor"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:6112","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6112","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P51617","url":"https://www.uniprot.org/uniprotkb/P51617/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000184216","url":"https://platform.opentargets.org/target/ENSG00000184216/associations","note":"association with cancer (MONDO_0004992) 0.66; per-cancer scores at or above 0.5: myeloproliferative neoplasm 0.58 (GraphQL API, CC0)"},{"label":"IntOGen IRAK1","url":"https://www.intogen.org/search?gene=IRAK1","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 1 medicine aimed at it (Pacritinib) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA IRAK1: RNA low tissue specificity; high antibody staining in 10 normal tissues; highest cancer staining carcinoid (1 of 4 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Multiple myeloma); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas IRAK1 tissue","url":"https://www.proteinatlas.org/ENSG00000184216-IRAK1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000184216 associations","url":"https://platform.opentargets.org/target/ENSG00000184216/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:6112","ensembl":"ENSG00000184216","uniprot":"P51617","entrez":"3654","firstDescribed":1996,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Cao et al, Science, 1996, \"IRAK: a kinase associated with the interleukin-1 receptor\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8599092/","biology":"Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signalling pathways. Is rapidly recruited by MYD88 to the receptor-signalling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. Location: Cytoplasm; Nucleus; Lipid droplet (UniProt). Locus Xq28 (HGNC).","whereFound":["Myeloproliferative neoplasms: Open Targets association 0.58 with myeloproliferative neoplasm (MONDO_0020076)","Multiple myeloma: IntOGen driver in 1 cohort (PCM)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/irak1/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"}],"drug":[{"id":"pacritinib","kind":"drug","name":"Pacritinib","route":"/drugs/pacritinib/"}]}}