NFE2L1 (Nuclear Factor, Erythroid 2 Like 1)
A key transcription factor regulating oxidative stress response, proteostasis, and metabolic homeostasis.
Gene Information Card
| Symbol | NFE2L1 |
|---|---|
| Full Name | Nuclear Factor, Erythroid 2 Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.32 |
| NCBI Gene ID | 4779 ncbi.nlm.nih.gov/gene/4779 |
| Ensembl ID | ENSG00000100030 |
| UniProt ID | Q14494 |
| OMIM ID | 163260 |
| HGNC ID | 7781 |
| Aliases | NRF1, TCF11, LCR-F1, HBZ17 |
Description
NFE2L1 (also known as NRF1) encodes a basic leucine zipper (bZIP) transcription factor that belongs to the cap'n'collar (CNC) family. It is a master regulator of proteasome subunit gene expression and plays a critical role in maintaining cellular redox homeostasis, lipid metabolism, and mitochondrial function. Unlike its paralog NFE2L2 (NRF2), NFE2L1 is constitutively expressed and is essential for embryonic development. It is activated by proteolytic cleavage in response to proteasome dysfunction and translocates to the nucleus to induce expression of antioxidant and proteostasis genes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Dysregulation of NFE2L1 alters proteasome activity and oxidative stress response, promoting tumor survival and chemoresistance. | COSMIC; PubMed studies |
| Neurodegenerative disorders | Impaired NFE2L1 function leads to proteotoxic stress and accumulation of damaged proteins, implicated in Parkinson's and Alzheimer's disease. | ClinVar; PubMed |
| Metabolic syndrome | NFE2L1 regulates lipid and glucose metabolism; variants are associated with insulin resistance and non-alcoholic fatty liver disease. | OMIM; PubMed |
| Proteasome-associated autoinflammatory syndromes | Loss-of-function mutations in NFE2L1 cause impaired proteasome assembly, leading to immune dysregulation. | ClinVar; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 9.8 | Medium |
| Brain | 7.2 | Medium |
| Heart | 6.1 | Medium |
| Lung | 5.4 | Low |
| Skeletal Muscle | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.3 | Hepatocellular carcinoma cell line |
| HEK293 | 11.0 | Embryonic kidney cells |
| SH-SY5Y | 8.5 | Neuroblastoma cell line |
| HeLa | 7.8 | Cervical cancer cells |
| A549 | 6.2 | Lung adenocarcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1246C>T (p.Arg416*) | Nonsense | <0.1% | Loss of function; truncated protein |
| c.823G>A (p.Glu275Lys) | Missense | 0.2% | Reduced DNA-binding affinity |
| c.1450_1452del (p.Lys484del) | In-frame deletion | <0.1% | Impaired nuclear translocation |
| c.1765C>T (p.Pro589Ser) | Missense | 0.3% | Altered transactivation activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the bZIP domain or disrupt nuclear localization signal (NLS) result in loss of transcriptional activity.
Gain of Function (GOF)
Missense mutations in the N-terminal domain that enhance protein stability or nuclear import may lead to constitutive activation, observed in some cancers.
Dominant Negative (DN)
Mutations that retain DNA-binding but lack transactivation domain can compete with wild-type NFE2L1, reducing target gene expression.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Proteasome (Reactome: R-HSA-1234176)
• NRF2-ARE signaling (KEGG: hsa05208)
• Cellular response to stress (Reactome: R-HSA-2262752)
• Metabolism of lipids (Reactome: R-HSA-556833)
Protein Summary
NFE2L1 is a 741-amino acid protein with a conserved CNC-bZIP domain. It is synthesized as an endoplasmic reticulum (ER) membrane-bound precursor that undergoes N-glycosylation and retrotranslocation to the cytosol. Upon proteasome impairment, it is cleaved by the protease DDI2, releasing an active N-terminal fragment that translocates to the nucleus. There, it heterodimerizes with small Maf proteins (e.g., MAFF, MAFG, MAFK) and binds to antioxidant response elements (ARE) to drive expression of proteasome subunits, antioxidant enzymes, and lipid metabolism genes. NFE2L1 is essential for maintaining proteostasis and is implicated in cancer, neurodegeneration, and metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFE2L1 Knockout HEK293 Cell Line | EDJ-KQ2298 | Human | 4779 | Details Get a Quote |
| NFE2L1 Knockout HeLa Cell Line | EDJ-KQ21339 | Human | 4779 | Details Get a Quote |
| NFE2L1 Knockout A-549 Cell Line | EDJ-KQ22665 | Human | 4779 | Details Get a Quote |
| NFE2L1 Knockout HCT 116 Cell Line | EDJ-KQ22666 | Human | 4779 | Details Get a Quote |
