Loading
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. This dossier gathers the 0 products (0 approved), 0 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of 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).
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 11-18% | Inactivating mutation | cBioPortal: 400 of 2,653, 15.1%, in luad_mskcc_2023_met_organotropism; 153 of 915, 16.7%, in lung_msk_2017; 102 of 566, 18.0%, in luad_tcga_pan_can_atlas_2018; 40 of 230, 17.4%, in luad_tcga_pub; 12 of 110, 10.9%, in luad_cptac_2020; 197 of 2,621, 7.5%, in nsclc_ctdx_msk_2022; 13 of 302, 4.3%, in luad_oncosg_2020; 1 of 232, 0.4%, in lung_nci_2022. In the immunotherapy cohort, 53 of 240, 22.1% (cBioPortal nsclc_pd1_msk_2018); deleterious KEAP1 mutations were 231 of 1,202 assessable patients, 19.2% (Ricciuti 2022). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
No product in the corpus is aimed at this target yet.
No trial in the corpus names this target or one of its products.
No recorded escape route names this target.
No pathway diagram carries this target as a node.
No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"KEAP1" OR ABSTRACT:"KEAP1" OR TITLE:"kelch like ECH associated protein 1" OR ABSTRACT:"kelch like ECH associated protein 1" OR TITLE:"Kelch-like ECH-associated protein 1" OR ABSTRACT:"Kelch-like ECH-associated protein 1" OR TITLE:"KIAA0132" OR ABSTRACT:"KIAA0132" OR TITLE:"MGC10630" OR ABSTRACT:"MGC10630" OR TITLE:"MGC1114" OR ABSTRACT:"MGC1114") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about KEAP1, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/keap1.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/keap1.json. Licence CC BY-NC 4.0.