NFKB1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the NFKB1 gene, its protein product, associated diseases, and expression patterns.
Gene Information Card
| Symbol | NFKB1 |
|---|---|
| Full Name | Nuclear factor kappa B subunit 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 4790 ncbi.nlm.nih.gov/gene/4790 |
| Ensembl ID | ENSG00000109320 |
| UniProt ID | P19838 |
| OMIM ID | 164011 |
| HGNC ID | 7794 |
| Aliases | NF-kB1, p105, p50, CVID12 |
Description
The NFKB1 gene encodes a 105 kDa protein (p105) that undergoes proteolytic processing to generate the p50 subunit of the NF-kappa-B transcription factor complex. NF-kappa-B is a key regulator of immune responses, inflammation, cell survival, and proliferation. The p50 subunit forms homo- or heterodimers with other NF-kappa-B family members (e.g., RelA/p65) and binds to kappa-B sites in DNA to modulate gene expression. NFKB1 is widely expressed and its dysregulation is linked to inflammatory diseases, immunodeficiencies, and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Common variable immunodeficiency (CVID) | Loss-of-function mutations in NFKB1 lead to haploinsufficiency, impairing NF-kappa-B signaling and antibody production. | ClinVar, OMIM |
| Inflammatory bowel disease (IBD) | NFKB1 variants are associated with altered NF-kappa-B activity, contributing to chronic intestinal inflammation. | ClinVar, literature |
| Rheumatoid arthritis | NFKB1 polymorphisms may influence susceptibility and severity through dysregulated inflammatory responses. | ClinVar, literature |
| Cancer (various types) | NFKB1 can act as an oncogene or tumor suppressor depending on context; mutations and altered expression affect cell survival and proliferation. | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | 12.5 | High |
| Spleen | 10.2 | High |
| Lymph node | 9.8 | High |
| Bone marrow | 8.5 | Medium |
| Lung | 6.3 | Medium |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.0 | High expression |
| HeLa (cervical cancer) | 12.0 | High expression |
| A549 (lung cancer) | 8.5 | Medium expression |
| MCF7 (breast cancer) | 6.0 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.748C>T (p.Arg250Ter) | Nonsense | Rare | Loss of function, leading to haploinsufficiency |
| c.959G>A (p.Arg320Gln) | Missense | Rare | Impaired DNA binding and transcriptional activity |
| c.1244G>A (p.Arg415Gln) | Missense | Rare | Reduced protein stability and function |
| c.1655C>T (p.Pro552Leu) | Missense | Rare | Altered dimerization and signaling |
Mutation functional classification
Loss of Function (LOF)
Most NFKB1 mutations are loss-of-function, leading to reduced p50 protein levels and impaired NF-kappa-B signaling, as seen in CVID.
Gain of Function (GOF)
Gain-of-function mutations are rare but may occur in certain cancers, leading to constitutive NF-kappa-B activation and enhanced cell survival.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming non-functional dimers that interfere with wild-type NF-kappa-B activity.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • protein dimerization activity |
| • regulation of inflammatory response | • apoptotic process |
| • immune response | • cell proliferation |
Pathways
• NF-kappa B signaling pathway
• Toll-like receptor signaling pathway
• Cytokine-cytokine receptor interaction
• Apoptosis
Protein Summary
The NFKB1 gene encodes a 105 kDa protein (p105) that is processed to generate the p50 subunit. p50 contains a Rel homology domain (RHD) responsible for DNA binding and dimerization. It lacks a transactivation domain, so p50 homodimers can repress transcription, while heterodimers with p65 (RelA) activate transcription. The protein is involved in the canonical NF-kappa-B pathway, where it is sequestered in the cytoplasm by I-kappa-B proteins and translocates to the nucleus upon stimulation. Post-translational modifications, such as phosphorylation and ubiquitination, regulate its processing and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFKB1 Knockout HEK293 Cell Line | EDJ-KQ17887 | Human | 4790 | Details Get a Quote |
| NFKB1 Knockout HeLa Cell Line | EDJ-KQ18032 | Human | 4790 | Details Get a Quote |
| NFKB1 Knockout A-549 Cell Line | EDJ-KQ18985 | Human | 4790 | Details Get a Quote |
| NFKB1 Knockout HCT 116 Cell Line | EDJ-KQ18986 | Human | 4790 | Details Get a Quote |
| NFKB1 Knockout U-87MG ATCC Cell Line | EDJ-KZ364 | Human | 4790 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
