NFE2 Gene: Nuclear Factor, Erythroid 2
A master regulator of erythroid and megakaryocytic gene expression
Gene Information Card
| Symbol | NFE2 |
|---|---|
| Full Name | Nuclear Factor, Erythroid 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.2 |
| NCBI Gene ID | 4778 ncbi.nlm.nih.gov/gene/4778 |
| Ensembl ID | ENSG00000123405 |
| UniProt ID | Q16621 |
| OMIM ID | 601490 |
| HGNC ID | 7778 |
| Aliases | NF-E2, p45 NF-E2 |
Description
NFE2 encodes a basic leucine zipper (bZIP) transcription factor that forms heterodimers with small Maf proteins (MAFF, MAFG, MAFK). It is essential for erythroid and megakaryocytic differentiation, regulating genes involved in hemoglobin synthesis, platelet production, and heme metabolism. NFE2 binds to the NF-E2 DNA motif (GCTGA(G/C)TCA) in the beta-globin locus control region and other target genes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Beta-thalassemia | Altered NFE2 binding to beta-globin LCR reduces globin expression | ClinVar, OMIM |
| Myeloproliferative neoplasms (MPN) | NFE2 overexpression or gain-of-function mutations drive megakaryocyte hyperplasia | COSMIC, PubMed |
| Erythroleukemia | Dysregulated NFE2 activity contributes to blocked erythroid differentiation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 45.2 | High |
| Spleen | 22.8 | Medium |
| Liver | 8.5 | Low |
| Whole Blood | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (erythroleukemia) | 78.3 | High expression; used in erythroid differentiation studies |
| HEL (erythroleukemia) | 65.1 | High expression; megakaryocytic lineage |
| HepG2 (hepatocellular) | 12.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.871C>T (p.Arg291Trp) | Missense | <0.1% | Reduced DNA binding; associated with beta-thalassemia |
| c.997_999dup (p.Lys333dup) | In-frame insertion | <0.1% | Gain-of-function; linked to MPN |
| c.1A>G (p.Met1Val) | Start loss | <0.1% | Loss of function; rare |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the bZIP domain (e.g., p.Arg291Trp) impair DNA binding and transactivation, reducing globin gene expression.
Gain of Function (GOF)
In-frame duplications (e.g., p.Lys333dup) enhance NFE2 stability and transcriptional activity, promoting megakaryocyte proliferation.
Dominant Negative (DN)
Not well documented; some bZIP mutants may interfere with heterodimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Erythropoiesis (Reactome: R-HSA-983231)
• Megakaryocyte development and platelet production (Reactome: R-HSA-983189)
• Transcriptional regulation by small Maf proteins (KEGG: hsa04630)
Protein Summary
NFE2 (p45 NF-E2) is a 373-amino acid transcription factor with a bZIP domain that dimerizes with small Maf proteins. It is predominantly expressed in hematopoietic tissues and is critical for erythroid and megakaryocytic gene expression. The protein activates beta-globin, porphobilinogen deaminase, and platelet factor 4. Mutations in NFE2 are associated with beta-thalassemia and myeloproliferative neoplasms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFE2L1 Knockout HEK293 Cell Line | EDJ-KQ2298 | Human | 4779 | Details Get a Quote |
| NFE2 Knockout HEK293 Cell Line | EDJ-KQ5334 | Human | 4778 | Details Get a Quote |
| NFE2L3 Knockout HEK293 Cell Line | EDJ-KQ6652 | Human | 9603 | Details Get a Quote |
| NFE2L2 Knockout HEK293 Cell Line | EDC90189 | Human | 4780 | Details Get a Quote |
| NFE2L2 Knockout A-549 Cell Line | EDC90777 | Human | 4780 | Details Get a Quote |
| NFE2L3 Knockout A-549 Cell Line | EDJ-KQ30940 | Human | 9603 | Details Get a Quote |
| NFE2L3 Knockout HCT 116 Cell Line | EDJ-KQ30941 | Human | 9603 | Details Get a Quote |
| NFE2L3 Knockout HeLa Cell Line | EDJ-KQ30942 | Human | 9603 | Details Get a Quote |
| NFE2L2 Knockout HCT 116 Cell Line | EDJ-KQ44611 | Human | 4780 | Details Get a Quote |
| NFE2L2 Knockout HeLa Cell Line | EDJ-KQ44612 | Human | 4780 | 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 |
| NFE2L2 Knockout Hep-G2 Cell Line | EDJ-KZ361 | Human | 4780 | Details Get a Quote |
| Nfe2l2 Knockout RAW 264.7 Cell Line | EDJ-KZ362 | Mouse | 18024 | Details Get a Quote |
