{"entity":{"id":"keap1","kind":"target","name":"KEAP1","aka":["kelch like ECH associated protein 1","Kelch-like ECH-associated protein 1","KIAA0132","MGC10630","MGC1114","MGC20887","MGC4407","MGC9454","INrf2","KLHL19"],"tldr":"KEAP1 (Kelch-like ECH-associated protein 1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Lung cancer, Hepatocellular carcinoma, Nasopharyngeal carcinoma and 3 more.","summary":"Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes.\n\nCIViC holds 6 clinical evidence items and 0 assertions across 2 variants, naming Cisplatin/Pembrolizumab/Pemetrexed Regimen, Chemotherapy, Palliative Radiation Therapy and Durvalumab Regimen and others. Open Targets scores its association with cancer at 0.76 (direct and indirect evidence; datatypes clinical 0.14, literature 0.99, genetic association 0.18, somatic mutation 0.96, animal model 0.37). IntOGen calls it a driver in 14 cohorts (7 activating, 7 loss-of-function), covering Cholangiocarcinoma, Hepatocellular Carcinoma, Lung Adenocarcinoma, Lung Squamous Cell Carcinoma, Nasopharyngeal Carcinoma, Non-Small Cell Lung Cancer.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:23177","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:23177"},{"label":"UniProt Q14145","url":"https://www.uniprot.org/uniprotkb/Q14145/entry"},{"label":"NCBI Gene 9817","url":"https://www.ncbi.nlm.nih.gov/gene/9817"},{"label":"Ensembl ENSG00000079999","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000079999"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["lung-cancer","hcc","nasopharyngeal","neuroendocrine","nsclc","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["hepatocellular-carcinoma-signalling","keap1-nrf2"],"terms":[],"trials":["nct05276726","nct06008093"],"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 0.14; IntOGen calls it an activating (Act) driver in 7 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 7 cohorts; CIViC holds 6 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" 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":"KEAP1","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:23177","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:23177","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q14145","url":"https://www.uniprot.org/uniprotkb/Q14145/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene KEAP1","url":"https://civicdb.org/features/7777","note":"6 evidence items, 0 assertions, 2 variants; diseases: Lung Non-small Cell Carcinoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000079999","url":"https://platform.opentargets.org/target/ENSG00000079999/associations","note":"association with cancer (MONDO_0004992) 0.76; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.69, neuroendocrine neoplasm 0.52, lung cancer 0.72 (GraphQL API, CC0)"},{"label":"IntOGen KEAP1","url":"https://www.intogen.org/search?gene=KEAP1","note":"driver in 14 cohorts (Act 7, LoF 7); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:23177","ensembl":"ENSG00000079999","uniprot":"Q14145","entrez":"9817","biology":"Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes. In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2. The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation. The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome. Location: Cytoplasm; Nucleus (UniProt). Locus 19p13.2 (HGNC).","whereFound":["Lung cancer: Open Targets association 0.72 with lung cancer (MONDO_0008903)","Hepatocellular carcinoma: IntOGen driver in 2 cohorts (HCC)","Nasopharyngeal carcinoma: IntOGen driver in 1 cohort (NPC)","Neuroendocrine tumours: Open Targets association 0.52 with neuroendocrine neoplasm (MONDO_0019496)","Non-small-cell lung cancer: Open Targets association 0.69 with non-small cell lung carcinoma (MONDO_0005233); CIViC evidence names this disease","Biliary tract cancer: IntOGen driver in 1 cohort (CHOL)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/keap1/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nasopharyngeal","kind":"cancer","name":"Nasopharyngeal carcinoma","route":"/cancers/nasopharyngeal/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"pathway":[{"id":"hepatocellular-carcinoma-signalling","kind":"pathway","name":"Hepatocellular carcinoma (KEGG map)","route":"/pathways/hepatocellular-carcinoma-signalling/"},{"id":"keap1-nrf2","kind":"pathway","name":"KEAP1-NRF2 antioxidant pathway","route":"/pathways/keap1-nrf2/"}],"trial":[{"id":"nct05276726","kind":"trial","name":"A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1","route":"/trials/nct05276726/"},{"id":"nct06008093","kind":"trial","name":"A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic NSCLC Patients With Non-squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS","route":"/trials/nct06008093/"}]}}