# KEAP1

Source: https://onco.cc/targets/keap1/  
OnCo record `keap1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: kelch like ECH associated protein 1; Kelch-like ECH-associated protein 1; KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19
- Tags: cancer-genes-wave
- Symbol: KEAP1
- Class: tumor-suppressor
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:23177: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:23177
- UniProt Q14145: https://www.uniprot.org/uniprotkb/Q14145/entry
- NCBI Gene 9817: https://www.ncbi.nlm.nih.gov/gene/9817
- Ensembl ENSG00000079999: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000079999

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Nasopharyngeal carcinoma](https://onco.cc/cancers/nasopharyngeal/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- pathways: [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [KEAP1-NRF2 antioxidant pathway](https://onco.cc/pathways/keap1-nrf2/)
- trials: [A Study of JAB-21822 in Advanced or Metastatic NSCLC With KRAS p.G12C and STK11 Co-mutation and Wild-type KEAP1](https://onco.cc/trials/nct05276726/), [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](https://onco.cc/trials/nct06008093/)

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