NFKBIB: A Key Regulator of NF-κB Signaling
Comprehensive genomic and functional analysis of the NFKB inhibitor beta gene
Gene Information Card
| Symbol | NFKBIB |
|---|---|
| Full Name | NFKB inhibitor beta |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 4793 ncbi.nlm.nih.gov/gene/4793 |
| Ensembl ID | ENSG00000104825 |
| UniProt ID | Q15653 |
| OMIM ID | 604495 |
| HGNC ID | 7798 |
| Aliases | IKBB, TRIP9, I-kappa-B-beta |
Description
The NFKBIB gene encodes I-kappa-B-beta (IκBβ), a member of the IκB family of proteins that inhibit the NF-κB transcription factor. IκBβ sequesters NF-κB complexes in the cytoplasm, preventing nuclear translocation and transcriptional activation. Phosphorylation and degradation of IκBβ in response to stimuli release NF-κB to regulate genes involved in immune response, inflammation, cell survival, and proliferation. NFKBIB is essential for fine-tuning NF-κB signaling and its dysregulation is linked to inflammatory diseases and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inflammatory bowel disease | Altered IκBβ expression disrupts NF-κB regulation, promoting chronic intestinal inflammation | PMID: 12163380 |
| Rheumatoid arthritis | Increased NFKBIB expression correlates with sustained NF-κB activation in synovial tissue | PMID: 15657137 |
| Multiple myeloma | Mutations in NFKBIB impair IκBβ function, leading to constitutive NF-κB activity and tumor growth | COSMIC: NFKBIB |
| Breast cancer | Loss of IκBβ expression enhances NF-κB signaling, promoting metastasis | PMID: 21804531 |
| Hodgkin lymphoma | NFKBIB deletions or mutations contribute to constitutive NF-κB activation in Hodgkin/Reed-Sternberg cells | COSMIC: NFKBIB |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Lung | 7.1 | Low |
| Colon | 6.5 | Low |
| Breast | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney, high expression |
| HeLa | 12.8 | Cervical carcinoma, moderate |
| K-562 | 18.4 | Leukemia, high expression |
| MCF7 | 7.6 | Breast cancer, low expression |
| A549 | 9.1 | Lung carcinoma, moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | 0.01% | Loss of start codon, likely loss of function |
| c.256C>T (p.Arg86Trp) | Missense | 0.02% | Alters IκBβ structure, impairs NF-κB binding |
| c.487_489del (p.Lys163del) | Deletion | 0.005% | In-frame deletion, reduced stability |
| c.700G>A (p.Glu234Lys) | Missense | 0.01% | Gain-of-function? Enhanced degradation |
| c.1000C>T (p.Arg334*) | Nonsense | 0.003% | Premature stop, loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that truncate or destabilize IκBβ (e.g., p.Met1?, p.Arg334*) reduce its ability to inhibit NF-κB, leading to constitutive NF-κB activation.
Gain of Function (GOF)
Mutations that enhance IκBβ degradation (e.g., p.Glu234Lys) may paradoxically increase NF-κB activity by reducing IκBβ levels.
Dominant Negative (DN)
Mutations that produce a stable but non-functional IκBβ (e.g., p.Arg86Trp) can sequester NF-κB without inhibiting it, blocking normal IκBα/IκBβ function.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004871 - signal transducer activity | • GO:0005515 - protein binding |
| • GO:0005737 - cytoplasm | • GO:0007250 - activation of NF-kappaB-inducing kinase activity |
| • GO:0010468 - regulation of gene expression | • GO:0032481 - negative regulation of type I interferon production |
| • GO:0043123 - positive regulation of I-kappaB kinase/NF-kappaB signaling | • GO:0051092 - positive regulation of NF-kappaB transcription factor activity |
Pathways
• NF-kappa B signaling pathway (KEGG: hsa04064)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• TNF signaling pathway (KEGG: hsa04668)
• B cell receptor signaling pathway (KEGG: hsa04662)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
Protein Summary
The NFKBIB gene encodes IκBβ (I-kappa-B-beta), a 356-amino-acid protein with ankyrin repeat domains that mediate binding to NF-κB dimers. IκBβ preferentially interacts with p50/c-Rel and p50/RelA complexes, retaining them in the cytoplasm. Unlike IκBα, IκBβ is resistant to signal-induced degradation and can be partially degraded via the proteasome after phosphorylation by IKKβ. IκBβ also contains a nuclear export sequence and can shuttle between nucleus and cytoplasm, contributing to dynamic regulation of NF-κB activity. Post-translational modifications include phosphorylation at Ser19 and Ser23, and ubiquitination at Lys21 and Lys22.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFKBIB Knockout HEK293 Cell Line | EDJ-KQ5337 | Human | 4793 | Details Get a Quote |
| NFKBIB Knockout HeLa Cell Line | EDJ-KQ27203 | Human | 4793 | Details Get a Quote |
| NFKBIB Knockout A-549 Cell Line | EDJ-KQ28431 | Human | 4793 | Details Get a Quote |
| NFKBIB Knockout HCT 116 Cell Line | EDJ-KQ28432 | Human | 4793 | Details Get a Quote |
| NFKBIB Knockout HAP1 Cell Line | EDC08264 | Human | 4793 | Details Get a Quote |
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