NFKB2: A Key Regulator of Immune and Inflammatory Responses
Comprehensive genomic and functional analysis of the NFKB2 gene, its role in immunodeficiency, autoimmunity, and cancer.
Gene Information Card
| Symbol | NFKB2 |
|---|---|
| Full Name | Nuclear factor kappa B subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 4791 ncbi.nlm.nih.gov/gene/4791 |
| Ensembl ID | ENSG00000077150 |
| UniProt ID | Q00653 |
| OMIM ID | 164012 |
| HGNC ID | 7795 |
| Aliases | p100, p52, LYT10, CVID10, H2TF1, NF-kB2 |
Description
NFKB2 encodes the p100 subunit of the NF-κB transcription factor complex. p100 is processed to p52, which heterodimerizes with RelB to regulate gene expression in immune responses, inflammation, cell survival, and lymphoid organ development. Mutations in NFKB2 cause common variable immunodeficiency (CVID) with autoimmunity, and are implicated in B-cell malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Common variable immunodeficiency 10 (CVID10) | Loss-of-function or dominant-negative mutations impair NF-κB signaling, leading to defective B-cell maturation and antibody production. | ClinVar, OMIM |
| Autoimmune lymphoproliferative syndrome-like disease | Dominant-negative mutations disrupt NF-κB2 processing, causing lymphoproliferation and autoimmunity. | OMIM, PubMed |
| B-cell non-Hodgkin lymphoma | Gain-of-function rearrangements (e.g., t(10;14)) produce truncated p100 that constitutively activates NF-κB. | COSMIC, PubMed |
| Multiple myeloma | NFKB2 rearrangements and amplifications contribute to NF-κB activation and tumor growth. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 28.5 | High |
| Spleen | 25.3 | High |
| Bone marrow | 18.7 | High |
| Lung | 8.2 | Medium |
| Colon | 6.1 | Medium |
| Brain | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Raji (Burkitt lymphoma) | 32.1 | High expression |
| K562 (leukemia) | 15.4 | Moderate expression |
| HeLa (cervical cancer) | 7.8 | Low expression |
| HEK293 (embryonic kidney) | 5.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2564delA (p.Lys855Argfs*5) | Frameshift | Rare | Loss of function; causes CVID10 |
| c.2557C>T (p.Arg853*) | Nonsense | Rare | Loss of function; causes CVID10 |
| c.2565_2566insA (p.Arg856Thrfs*4) | Frameshift | Rare | Loss of function; causes CVID10 |
| c.2567G>A (p.Arg856Gln) | Missense | Rare | Dominant negative; impairs p100 processing |
| t(10;14)(q24;q32) | Translocation | Rare | Gain of function; truncates p100, constitutive NF-κB activation in B-cell lymphoma |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the C-terminal ankyrin repeat domain, preventing p100 processing and nuclear translocation.
Gain of Function (GOF)
Chromosomal rearrangements (e.g., t(10;14)) that remove the C-terminal domain, producing a constitutively active p52 that drives oncogenic NF-κB signaling.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg856Gln) that disrupt p100 processing and inhibit wild-type NF-κB2 function, leading to immunodeficiency.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NF-kappa B signaling pathway (KEGG hsa04064)
• TNF signaling pathway (KEGG hsa04668)
• B cell receptor signaling pathway (KEGG hsa04662)
• Toll-like receptor signaling pathway (KEGG hsa04620)
Protein Summary
NFKB2 encodes the p100 protein (UniProt Q00653), a member of the NF-κB family. p100 contains an N-terminal Rel homology domain (RHD) for DNA binding and dimerization, and a C-terminal ankyrin repeat domain that inhibits nuclear translocation. Upon IKK-mediated phosphorylation, p100 is partially proteolyzed to p52, which translocates to the nucleus as a heterodimer with RelB. This complex regulates genes involved in immunity, inflammation, and cell survival. Aberrant processing or mutation of NFKB2 leads to immunodeficiency and lymphoproliferative disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFKB2 Knockout HEK293 Cell Line | EDJ-KQ579 | Human | 4791 | Details Get a Quote |
| NFKB2 Knockout A-549 Cell Line | EDJ-KQ18988 | Human | 4791 | Details Get a Quote |
| NFKB2 Knockout HCT 116 Cell Line | EDJ-KQ18989 | Human | 4791 | Details Get a Quote |
| NFKB2 Knockout HeLa Cell Line | EDJ-KQ18990 | Human | 4791 | Details Get a Quote |
