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NFE2L2 (Nuclear factor erythroid 2-related factor 2) is a protein that switches other genes on and off. 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, Head and neck squamous cell carcinoma and 5 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.
Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralising reactive electrophiles. In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex. In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerisation with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes. The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes. The NFE2L2/NRF2 pathway is also activated during the unfolded protein response (UPR), contributing to redox homeostasis and cell survival following endoplasmic reticulum stress. May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region. Location: Cytoplasm, cytosol; Nucleus (UniProt). Locus 2q31.2 (HGNC).
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 12-15% | Hotspot mutation in the KEAP1-binding degrons | cBioPortal: 72 of 484, 14.9%, in lusc_tcga_pan_can_atlas_2018; 27 of 178, 15.2%, in lusc_tcga_pub; 13 of 108, 12.0%, in lusc_cptac_2021; 84 of 1,144, 7.3%, in the combined nsclc_tcga_broad_2016; against 18 of 566, 3.2%, in lung adenocarcinoma. The mutations cluster tightly in the two motifs KEAP1 grips: E79Q (7 records), R34G (6), G31A (5), R34Q (5), D29H (5), R34P (5), D29N (5) and L30F (4) in lusc_tcga_pan_can_atlas_2018. | 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:"NFE2L2" OR ABSTRACT:"NFE2L2" OR TITLE:"NFE2 like bZIP transcription factor 2" OR ABSTRACT:"NFE2 like bZIP transcription factor 2" OR TITLE:"Nuclear factor erythroid 2-related factor 2" OR ABSTRACT:"Nuclear factor erythroid 2-related factor 2" OR TITLE:"NRF2" OR ABSTRACT:"NRF2" OR TITLE:"NRF-2" OR ABSTRACT:"NRF-2") 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 NFE2L2, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/nfe2l2.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/nfe2l2.json. Licence CC BY-NC 4.0.