Affinage

NFKB2

Nuclear factor NF-kappa-B p100 subunit · UniProt Q00653

Length
900 aa
Mass
96.7 kDa
Annotated
2026-06-10
89 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFKB2 encodes a bifunctional NF-κB precursor, p100, whose N-terminal Rel homology domain confers κB-site DNA binding while its C-terminal ankyrin repeats act as an intramolecular and intermolecular IκB-like inhibitor (PMID:1760839, PMID:8413211). In its full-length cytoplasmic form, p100 (identical to the MHC class I enhancer factor H2TF1) sequesters NF-κB subunits including c-Rel, p50, and RelA/p65, both by direct Rel-domain dimerization and by capturing preformed dimers through its ankyrin repeats—the basis of its bona fide IκBδ activity within high-molecular-weight complexes that restrain all NF-κB isoforms (PMID:8413211, PMID:8360178, PMID:7478612, PMID:19524538). Signal-dependent processing removes the ankyrin domain to release the active p52 subunit: p52 has no intrinsic transactivation and homodimers repress transcription, but p52/RelA heterodimers bind κB sites with high affinity and strongly activate transcription (PMID:8441377, PMID:8108136). Processing proceeds via cotranslational proteasomal cleavage gated by a glycine-rich region (PMID:10597218) and is controlled by C-terminal phosphorylation (including Ser866) that licenses GSK3-dependent, SCF(Fbw7)-mediated ubiquitination and degradation of the inhibitory C-terminus (PMID:22708077, PMID:24888602). p52 also represses the NFKB2 promoter, forming a negative feedback loop that opposes RelA-driven transactivation of the gene (PMID:7541912). Two distinct classes of disease-causing mutation illustrate this architecture: C-terminal truncating or phosphorylation-site mutations that block processing generate degradation-resistant p100 "super-repressors" which inhibit RelA and ablate both canonical and noncanonical signaling (PMID:18025196, PMID:24140114, PMID:33107914), whereas Rel-domain nonsense mutations remove the ankyrin domain to yield constitutively nuclear, transcriptionally active species (PMID:7651435, PMID:28778864). NFKB2 mutations cause common variable immunodeficiency, and the IκBδ activity of degradation-resistant p100 in nonhematopoietic cells—including thymic stroma and pituitary corticotroph progenitors—drives autoimmunity and the endocrine features of DAVID syndrome (PMID:24140114, PMID:33107914, PMID:39607428).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1991 High

    Established the domain logic of NFKB2: an N-terminal Rel DNA-binding domain held in check by C-terminal ankyrin repeats, answering how one gene product could be both a transcription factor and an inhibitor.

    Evidence cDNA cloning and in vitro EMSA with domain deletions; translocation-derived ankyrin-less fusion

    PMID:1760839

    Open questions at the time
    • Did not resolve how the ankyrin domain is removed in cells
    • No in vivo processing mechanism
  2. 1993 High

    Defined p100 as a cytoplasmic IκB-like sequestering molecule and identified it as the MHC class I enhancer factor H2TF1, reconciling its inhibitory and DNA-binding identities.

    Evidence Subcellular fractionation, co-IP, EMSA, affinity purification with peptide sequencing and KD determination in HeLa cells

    PMID:8360178 PMID:8413211

    Open questions at the time
    • Did not define the signal that releases sequestered dimers
    • Endogenous complex stoichiometry unresolved
  3. 1993 High

    Showed that processed p52 acquires activating function only through heterodimerization, distinguishing repressive homodimers from transactivating p52/RelA complexes.

    Evidence Scatchard analysis, in vitro transcription, recombinant binding assays

    PMID:8441377

    Open questions at the time
    • In vitro affinities not linked to cellular target gene selectivity
  4. 1994 High

    Demonstrated that signal-induced processing converts cytoplasmic p100 to nuclear p52, and that tumor-derived C-terminal truncations abolish repression while remaining DNA-binding—linking ankyrin loss to oncogenic constitutive activity.

    Evidence Immunofluorescence, EMSA, reporter assays, tumor-derived constructs (HUT78 p84/85)

    PMID:8036016 PMID:8108136 PMID:8208540

    Open questions at the time
    • Processing protease and signaling input not yet identified
    • Mechanism of constitutive nuclear retention undefined
  5. 1994 Medium

    Connected viral oncogenesis to NFKB2, showing HTLV-I Tax associates with p100 and drives its processing to sustain constitutive NF-κB activity.

    Evidence Co-IP, immunoblotting, EMSA in Tax-expressing cells

    PMID:8108127

    Open questions at the time
    • Correlative processing data, single lab
    • Direct Tax-induced cleavage not reconstituted
  6. 1995 Medium

    Identified the NFKB2 promoter negative feedback loop—RelA activates the gene while p52 represses it—explaining homeostatic control of pathway output.

    Evidence EMSA and CAT reporter co-transfection with NF-κB effectors

    PMID:7541912

    Open questions at the time
    • Single lab promoter-reporter assays
    • In vivo relevance of feedback not tested
  7. 1999 High

    Defined the cis-determinants of inefficient p100 processing, showing a glycine-rich region directs cotranslational proteasomal cleavage and flanking sequences limit p52 yield.

    Evidence p100/p105 chimeras, proteasome inhibitors, in vitro translation

    PMID:10597218

    Open questions at the time
    • Did not identify the E3 ligase or signal that triggers processing
  8. 2009 High

    Resolved the biochemical basis of IκBδ activity, showing p100 forms high-MW complexes binding NF-κB via two modes (Rel dimerization and ankyrin capture of preformed dimers) that regulate all isoforms.

    Evidence Endogenous complex characterization, recombinant reconstitution, gel filtration, IP

    PMID:19524538

    Open questions at the time
    • Structural model of the complex not determined
    • Dynamics of release upon signaling not captured
  9. 2007 High

    Established in vivo that unprocessable p100 acts as a super-repressor of RelA, demonstrating p100 inhibits canonical as well as noncanonical signaling and is required for lymphoid organ development.

    Evidence Nfkb2 processing-deficient knock-in mouse, histology, signaling assays

    PMID:18025196

    Open questions at the time
    • Phosphorylation/degron details of the block not molecularly mapped
  10. 2012 High

    Identified SCF(Fbw7) as the GSK3-dependent E3 ligase governing p100 degradation, closing the loop from C-terminal phosphorylation to proteasomal turnover.

    Evidence Fbw7-null cells, ubiquitination assays, rescue with WT vs mutant Fbw7, T cell conditional knockout

    PMID:22708077

    Open questions at the time
    • Precise phosphodegron residues recognized by Fbw7 not fully enumerated
    • Kinase upstream of GSK3 priming not defined here
  11. 2013 High

    Established NFKB2 C-terminal mutations as a genetic cause of common variable immunodeficiency by showing they block p100 phosphorylation, processing, and p52 nuclear translocation.

    Evidence Exome sequencing, immunoblot and immunofluorescence of patient B cells

    PMID:24140114

    Open questions at the time
    • Tissue-specific contributions to disease not dissected in patients
  12. 2014 Medium

    Pinpointed Ser866 as the critical regulatory phosphorylation site, with missense and frameshift mutations abolishing its phosphorylation to block processing and cause B-cell deficiency.

    Evidence Western blot, immunophenotyping, Sanger sequencing of patient cells (D865G; D865Vfs*17)

    PMID:24888602 PMID:25237204

    Open questions at the time
    • Single-lab patient analyses
    • Kinase phosphorylating Ser866 not identified
  13. 2017 High

    Distinguished a second mutational class—Rel-domain nonsense mutations—that produce constitutively nuclear gain-of-function proteins activating both pathways, contrasting with C-terminal loss-of-function super-repressors.

    Evidence Reporter assays, immunoblot, IHC, cytokine assays in HEK293T and patient PBMCs (E418X, R635X)

    PMID:28778864

    Open questions at the time
    • Clinical penetrance differences between mutation classes not fully resolved
  14. 2021 High

    Established that degradation-resistant p100, not p52 loss, drives autoimmunity, acting through IκB function in nonhematopoietic cells and causing thymic medullary hypoplasia.

    Evidence Graded degron-mutant mouse allelic series, thymic histology, TCR repertoire, bone marrow transplantation

    PMID:33107914

    Open questions at the time
    • Specific thymic stromal targets of p100 IκB activity not enumerated
  15. 2021 High

    Showed noncanonical Nfkb2 signaling amplifies canonical RelA-driven inflammation by supplying latent NF-κB dimers, providing a crosstalk mechanism in intestinal epithelium.

    Evidence Intestinal epithelial cell-specific conditional mouse colitis model with epistasis analysis

    PMID:34155144

    Open questions at the time
    • Quantitative contribution of dimer supplementation to human disease unknown
  16. 2024 High

    Demonstrated a direct, cell-autonomous role for NFKB2 in human pituitary corticotroph development, explaining the endocrine features of DAVID syndrome.

    Evidence CRISPR-edited DAVID-mutant hiPSC pituitary organoids, gene expression analysis

    PMID:39607428

    Open questions at the time
    • Direct transcriptional targets of NFKB2 in corticotrophs not mapped
  17. 2025 Medium

    Linked NFKB2 to tumor immune evasion, showing TRAIL/DR5/caspase-8 signaling engages the noncanonical pathway to drive chemokine production and neutrophil recruitment in TNBC.

    Evidence RNAseq, siRNA knockdown, chemotaxis assays, TNBC xenografts, immunoblot

    PMID:40187604

    Open questions at the time
    • Single-lab study
    • Direct NFKB2-driven chemokine gene occupancy not shown
  18. 2026 Medium

    Identified B3GNT3 as a noncatalytic interactor that promotes p100 phosphorylation and processing, defining a new upstream activator of noncanonical signaling in cancer.

    Evidence Reciprocal co-IP/MS, catalytic-inactive B3GNT3 mutant, NFKB2 knockout rescue, xenografts

    PMID:41838238

    Open questions at the time
    • Single lab; mechanism by which B3GNT3 promotes phosphorylation undefined
    • Reciprocal validation in physiological context limited

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the kinase that phosphorylates Ser866 to prime SCF(Fbw7) recognition, and the structural basis of p100 IκBδ high-MW complexes, remain unresolved.
  • Ser866 kinase not identified in the corpus
  • No structural model of the p100–NF-κB inhibitory complex
  • Tissue-specific nonhematopoietic target genes incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 4 GO:0140313 molecular sequestering activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3
Partners
B3GNT3FBXW7NFKB1RELRELARELB
Complex memberships
H2TF1NF-κB p52/RelA heterodimerp100 IκBδ high-molecular-weight complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 The LYT-10 (NFKB2) protein contains an N-terminal rel (DNA-binding) domain homologous to NF-κB p50, a poly-G region, and C-terminal ankyrin-like repeat domains. The ankyrin domain inhibits DNA binding in vitro; removal of the ankyrin domain activates DNA binding to κB sequences. Chromosomal translocation-generated LYT-10–Cα1 fusion retains the rel domain, lacks the ankyrin domain, and binds κB sequences constitutively. cDNA cloning, in vitro DNA-binding assay (EMSA), domain deletion analysis Cell High 1760839
1993 NF-κB p100 (NFKB2/Lyt-10) functions as an IκB-like molecule: it is localized in the cytoplasm of HeLa cells where it associates with c-Rel, p50, and p65 (RelA), and its overexpression sequesters p65 in the cytoplasm, reducing nuclear p65 DNA-binding activity. p100 is also a component of the MHC class I transcription factor H2TF1. Subcellular fractionation, immunoblotting, EMSA, transient transfection reporter assay Molecular and cellular biology High 8413211
1993 H2TF1, the ubiquitous MHC class I κB enhancer-binding factor, is the full-length p100 product (NF-κB2 p100) encoded by nfkb2. Purified H2TF1 binds the MHC κB site with high affinity (KD = 3 × 10⁻¹¹ M), contradicting earlier reports that p100 did not bind DNA. Affinity chromatography purification, peptide sequencing, specific antiserum reactivity, in vitro DNA-binding assay The Journal of biological chemistry High 8360178
1993 NFKB2 p49/p52 forms a heterodimer with RelA (p65) that binds the HIV κB site with ~6-fold higher affinity (KD = 11.8 pM) than p49 homodimer alone (KD = 69.1 pM). The p49/p65 heterodimer stimulates in vitro transcription 18-fold. IκB-α (MAD-3) inhibits DNA binding of p49/p65 and p50/p65 heterodimers but stimulates binding of p49 or p50 alone. Scatchard analysis, in vitro transcription assay, recombinant protein binding assays, transient transfection Molecular and cellular biology High 8441377
1994 C-terminal truncations of NFKB2 found in lymphoid malignancies (p84/85 in HUT78 T-cell lymphoma) result in constitutive nuclear localization of the unprocessed protein, altered NF-κB complex composition, and loss of transcriptional repressor function; the truncated proteins bind κB sites but cannot repress NF-κB-mediated transcription. Northern blot, immunoprecipitation, EMSA, immunofluorescence, transient co-transfection reporter assay Oncogene High 8036016 8208540
1994 NFKB2 p100 is constitutively cytoplasmic; TPA-induced NF-κB activation causes cytoplasmic-to-nuclear translocation of the processed p52 form. p52 alone preferentially binds H2/HLA-κB sites over HIV/IgK-κB sites, but efficiently binds both when heterodimerized with RelA (p65). p52 homodimers have no intrinsic transactivation; they down-regulate p65-driven transcription, whereas p65/p52 heterodimers stimulate it. Immunofluorescence, EMSA, transient co-transfection reporter assay Oncogene High 8108136
1994 In HTLV-I–infected and Tax-expressing cells, NFKB2 (p100) is overexpressed and physically associated with c-Rel and with the Tax protein. Tax-dependent processing of p100 to p52 correlates with constitutive nuclear NF-κB activity, suggesting Tax drives NFKB2 processing as a mechanism of constitutive NF-κB activation. Co-immunoprecipitation, immunoblotting, EMSA Oncogene Medium 8108127
1995 Tumor-associated NFKB2 mutants (p85 and lyt-10Cα) lacking the ankyrin domain are constitutively nuclear, bind κB sites in unprocessed form, activate transcription via heterodimerization with RelA/p65, and have lost the transcriptional repression activity of normal p52. They can independently transactivate κB reporter genes in a manner not further stimulated by Bcl-3. Immunofluorescence, UV-crosslinking immunoprecipitation of DNA-protein adducts, transient co-transfection reporter assay Molecular and cellular biology High 7651435
1995 Overexpressed p100 (NFKB2) in human breast cancer cells sequesters p50/p65 heterodimers in the cytoplasm via co-immunoprecipitation, acting as a cytoplasmic IκB-like inhibitor; most p65 is complexed with p100 rather than IκB-α in high-p100 cells. Co-immunoprecipitation, immunoblotting, subcellular fractionation Oncogene Medium 7478612
1995 The NFKB2 promoter contains six κB sites (five capable of binding NF-κB complexes in vitro). RelA transactivates the NFKB2 promoter in a dose-dependent manner, while NF-κB p52 acts as a repressor of its own gene promoter, establishing a negative feedback regulatory circuit. EMSA, transient transfection with CAT reporter, co-transfection with NF-κB effector plasmids Nucleic acids research Medium 7541912
1999 p52 is generated principally by cotranslational proteasomal processing of p100, dependent on a glycine-rich region (GRR) upstream of the p52 C-terminus; repositioning the GRR alters the site of proteasome cleavage. Sequences downstream of the GRR, flanking the processing site, confer the characteristically inefficient p52 generation from p100 compared to the balanced p50/p105 processing of NFKB1. p100/p105 chimera constructs, proteasome inhibitor experiments, immunoblotting, in vitro translation Oncogene High 10597218
2009 p100 assembles into high-molecular-weight complexes in the cytoplasm that bind NF-κB subunits in two modes: (1) direct dimerization via Rel homology domains and (2) interaction of p100 ankyrin repeats with preformed NF-κB dimers, thereby mediating bona fide IκBδ activity. These complexes regulate all NF-κB isoforms. Biochemical characterization of endogenous cytoplasmic complexes, purified recombinant protein reconstitution, gel filtration, immunoprecipitation Molecular cell High 19524538
2007 A point mutation in Nfkb2 that prevents processing of p100 to p52 generates a 'super-repressor' phenotype: signaling through the noncanonical pathway is ablated due to p52 absence, causing disorganized splenic architecture and disrupted B cell development. Furthermore, the unprocessed p100 interacts with RelA, preventing RelA dimer activation in response to both canonical and noncanonical stimuli, resulting in defective lymph node formation and altered bone homeostasis. Mouse genetic model (knock-in point mutation), immunoblotting, histological analysis, signaling assays Journal of immunology High 18025196
2012 SCF(Fbw7) is the E3 ubiquitin ligase that governs ubiquitination and proteasomal destruction of NFkB2/p100 in a GSK3-dependent manner. In Fbw7-null cells, elevated p100 reduces NFkB signaling and increases TNFα-induced cell death; reintroduction of wild-type but not disease-derived mutant Fbw7 rescues NFkB activity. T cell-specific Fbw7 depletion reduces NFkB activity and perturbs T cell differentiation. Genetic knockout cells (Fbw7-/-), immunoblotting, ubiquitination assay, T cell-specific conditional knockout mouse model Cell reports High 22708077
2013 Heterozygous C-terminal frameshift and nonsense mutations in NFKB2 (p.Lys855Serfs*7 and p.Arg853*) affect phosphorylation and proteasomal processing of p100, blocking p52 nuclear translocation. This establishes the noncanonical NF-κB signaling pathway as a genetic cause of common variable immunodeficiency. Exome sequencing, immunoblot analysis, immunofluorescence microscopy of patient B cells American journal of human genetics High 24140114
2014 A missense mutation (D865G) in NFKB2 causes failure of p100 phosphorylation, blocking its processing to p52 and disrupting both canonical and noncanonical NF-κB pathways; this leads to severe mature and transitional B-cell deficiency. Western blotting, immunophenotyping, patient-derived cells Blood Medium 25237204
2014 An 8 bp C-terminal frameshift deletion in NFKB2 (p.Asp865Valfs*17) mutates Ser866 to Arg, leaving p100 unphosphorylated at this critical regulatory position, thereby abrogating p100 processing and nuclear translocation of p52. Western blot, Sanger sequencing, flow cytometry (B cell immunophenotyping), patient cell analysis Journal of clinical immunology Medium 24888602
2015 NF-κB2/p52 directly transcriptionally activates EZH2 expression in melanoma cells. Inhibition of the noncanonical NF-κB pathway by targeting NF-kB2/p52 or the upstream kinase NIK decreases EZH2, restoring the senescence program. Overexpression of NF-kB2/p52 in normal melanocytes prevents stress- and oncogene-induced senescence. siRNA knockdown, overexpression, mouse xenograft models, ChIP/transcriptional activation assays (implied by direct transcriptional activation claim) Oncogene Medium 26364600
2017 Novel nonsense NFKB2 mutations within the Rel homology domain (E418X and R635X) cause constitutive nuclear localization of truncated proteins and activation of both canonical and noncanonical NF-κB pathways, distinct from C-terminal mutations that produce unprocessable p100 super-repressor. Flow cytometry, immunoblotting, immunohistochemistry, luciferase reporter assay, real-time PCR, multiplex cytokine assay in transfected HEK293T cells and patient PBMCs Blood High 28778864
2021 Nfkb2-mediated noncanonical signaling in intestinal epithelial cells escalates the RelA-driven proinflammatory gene response by supplementing latent NF-κB dimers to the canonical module, exacerbating inflammatory cell infiltration and colon pathologies. Cell-autonomous Nfkb2 signaling increases available latent NF-κB dimers, linking noncanonical signaling to canonical RelA-driven inflammation. Mouse model of experimental colitis, conditional intestinal epithelial cell-specific genetic manipulation, mechanistic studies of latent dimer supplementation Proceedings of the National Academy of Sciences High 34155144
2021 Severe p100-degradation resistance (due to mutations in the p100 degron required for signal-dependent degradation) causes thymic medullary hypoplasia and autoimmune disease, while absence of both p100 and p52 does not. Autoimmunity arises from the IκB function of degradation-resistant p100 in nonhematopoietic cells, not from p52 deficiency. Mouse genetic models with graded degron mutations, thymic histology, T cell receptor repertoire analysis, bone marrow transplantation The Journal of experimental medicine High 33107914
2024 NFKB2 mutations directly impair human pituitary corticotroph development: pituitary organoids derived from CRISPR/Cas9-edited hiPSCs harboring DAVID patient NFKB2 mutations show changes in pituitary progenitor genes (HESX1, PITX1, LHX3), hypothalamic secreted factors (BMP4, FGF8, FGF10), lineage precursor genes (TBX19, POU1F1), and corticotroph terminal differentiation markers (PCSK1, POMC), with drastic reduction in corticotroph numbers. CRISPR/Cas9-edited human iPSC-derived pituitary organoids, gene expression analysis eLife High 39607428
2026 B3GNT3 physically interacts with NFKB2/p100 and facilitates its phosphorylation, processing into p52, and nuclear accumulation, thereby activating noncanonical NF-κB signaling. This interaction is independent of B3GNT3 glycosyltransferase activity. Genetic ablation of NFKB2 reverses the oncogenic effects of B3GNT3. Co-immunoprecipitation coupled with mass spectrometry, co-IP, catalytic inactive mutant of B3GNT3, NFKB2 knockout, immunoblotting, xenograft models Cellular oncology Medium 41838238
2025 TRAIL-induced cytokine production (CXCLs 1, 2, 3, 8, 11 and IL-6) in triple negative breast cancer cells is mediated predominantly through death receptor 5, caspase-8, and the noncanonical NFKB2 pathway. These cytokines promote neutrophil chemotaxis and immune suppression. In vivo TRAIL treatment activates the NFkB2 pathway, elevates cytokine production, and increases neutrophil tumor recruitment. RNAseq, siRNA knockdown, in vitro neutrophil chemotaxis assays, TNBC xenograft mouse models, immunoblotting Cancer letters Medium 40187604

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. Cell 403 1760839
2013 Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency. American journal of human genetics 197 24140114
2009 The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes. Molecular cell 132 19524538
1993 Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3). Molecular and cellular biology 128 8441377
1995 Highly-expressed p100/p52 (NFKB2) sequesters other NF-kappa B-related proteins in the cytoplasm of human breast cancer cells. Oncogene 122 7478612
1993 NF-kappa B p100 (Lyt-10) is a component of H2TF1 and can function as an I kappa B-like molecule. Molecular and cellular biology 121 8413211
2019 Clinical and Immunological Phenotype of Patients With Primary Immunodeficiency Due to Damaging Mutations in NFKB2. Frontiers in immunology 118 30941118
1993 Structural alterations of the NF-kappa B transcription factor lyt-10 in lymphoid malignancies. Oncogene 117 8378093
1999 The generation of nfkb2 p52: mechanism and efficiency. Oncogene 91 10597218
1994 Heterogeneous chromosomal aberrations generate 3' truncations of the NFKB2/lyt-10 gene in lymphoid malignancies. Blood 90 7949142
1995 Structural and functional characterization of the promoter regions of the NFKB2 gene. Nucleic acids research 83 7541912
2014 Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood 82 25237204
1994 Rearrangement and altered expression of the NFKB-2 gene in human cutaneous T-lymphoma cells. Oncogene 80 8036016
1994 Overproduction of NFKB2 (lyt-10) and c-Rel: a mechanism for HTLV-I Tax-mediated trans-activation via the NF-kappa B signalling pathway. Oncogene 77 8108127
1995 Rearranged NFKB-2 genes in lymphoid neoplasms code for constitutively active nuclear transactivators. Molecular and cellular biology 76 7651435
2012 SCF(Fbw7) modulates the NFkB signaling pathway by targeting NFkB2 for ubiquitination and destruction. Cell reports 75 22708077
2007 A novel mutation in the Nfkb2 gene generates an NF-kappa B2 "super repressor". Journal of immunology (Baltimore, Md. : 1950) 69 18025196
2014 Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies. BMC medical genetics 67 25524009
2014 Novel NFKB2 mutation in early-onset CVID. Journal of clinical immunology 64 24888602
1994 Rearranged NFKB2 gene in the HUT78 T-lymphoma cell line codes for a constitutively nuclear factor lacking transcriptional repressor functions. Oncogene 62 8208540
2017 Novel nonsense gain-of-function NFKB2 mutations associated with a combined immunodeficiency phenotype. Blood 60 28778864
2014 Combined immune deficiency in a patient with a novel NFKB2 mutation. Journal of clinical immunology 53 25205549
1994 Mechanism of expression and role in transcriptional control of the proto-oncogene NFKB-2/LYT-10. Oncogene 50 8108136
2021 An epithelial Nfkb2 pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module. Proceedings of the National Academy of Sciences of the United States of America 49 34155144
2005 High levels of p105 (NFKB1) and p100 (NFKB2) proteins in HPV16-transformed keratinocytes: role of E6 and E7 oncoproteins. Virology 47 15629778
2016 NFKB2 mutation in common variable immunodeficiency and isolated adrenocorticotropic hormone deficiency: A case report and review of literature. Medicine 46 27749582
1992 Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2. Genomics 45 1612589
2015 NF-kB2 induces senescence bypass in melanoma via a direct transcriptional activation of EZH2. Oncogene 44 26364600
1992 Chromosomal localization of the genes encoding the p50/p105 subunits of NF-kappa B (NFKB2) and the I kappa B/MAD-3 (NFKBI) inhibitor of NF-kappa B to 4q24 and 14q13, respectively. Genomics 44 1427874
1997 Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is tumorigenic in murine fibroblasts. Oncogene 40 9150386
1996 The involvement of the candidate proto-oncogene NFKB2/lyt-10 in lymphoid malignancies. Leukemia & lymphoma 30 9021684
2010 Myc suppression of Nfkb2 accelerates lymphomagenesis. BMC cancer 28 20598117
1998 Regulation of p100 (NFKB2) expression in human monocytes in response to inflammatory mediators and lymphokines. Leukemia 26 9529131
1993 Purification of the major histocompatibility complex class I transcription factor H2TF1. The full-length product of the nfkb2 gene. The Journal of biological chemistry 26 8360178
2019 Novel Heterozygous Mutation in NFKB2 Is Associated With Early Onset CVID and a Functional Defect in NK Cells Complicated by Disseminated CMV Infection and Severe Nephrotic Syndrome. Frontiers in pediatrics 25 31417880
1997 Identification of a novel gene, PSD, adjacent to NFKB2/lyt-10, which contains Sec7 and pleckstrin-homology domains. Genomics 25 9417912
2021 Nfkb2 variants reveal a p100-degradation threshold that defines autoimmune susceptibility. The Journal of experimental medicine 24 33107914
2022 NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications. The Journal of allergy and clinical immunology 22 36509151
1995 bcl-1, bcl-2, p53, c-myc, and lyt-10 analysis in cutaneous lymphomas. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer 22 7597296
2022 Targeting TKI-Activated NFKB2-MIF/CXCLs-CXCR2 Signaling Pathways in FLT3 Mutated Acute Myeloid Leukemia Reduced Blast Viability. Biomedicines 21 35625776
2020 NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors: Results from the REPAIR consortium. Scientific reports 20 32152480
2019 NFKB2 regulates human Tfh and Tfr pool formation and germinal center potential. Clinical immunology (Orlando, Fla.) 19 31751612
2017 A Case Report of Hypoglycemia and Hypogammaglobulinemia: DAVID Syndrome in a Patient With a Novel NFKB2 Mutation. The Journal of clinical endocrinology and metabolism 18 28472507
2010 Role of NFKB2 on the early myeloid differentiation of CD34+ hematopoietic stem/progenitor cells. Differentiation; research in biological diversity 18 20708837
2017 Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype. Oncogene 17 28368397
2000 Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes. Oncogene 17 10713675
2023 IRP1 mediated ferroptosis reverses temozolomide resistance in glioblastoma via affecting LCN2/FPN1 signaling axis depended on NFKB2. iScience 16 37520713
2021 NFKB2 inhibits NRG1 transcription to affect nucleus pulposus cell degeneration and inflammation in intervertebral disc degeneration. Mechanisms of ageing and development 15 34023356
2019 Fatal Enteroviral Encephalitis in a Patient with Common Variable Immunodeficiency Harbouring a Novel Mutation in NFKB2. Journal of clinical immunology 15 30927119
2024 Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review. Journal of clinical immunology 14 38990428
1997 Germline configuration of nfkb2, c-rel and bcl3 in childhood acute lymphoblastic leukemia (ALL). Leukemia 14 9264393
2019 Severe Facial Herpes Vegetans and Viremia in NFKB2-Deficient Common Variable Immunodeficiency. Frontiers in pediatrics 13 30941333
2020 A Nonsense N -Terminus NFKB2 Mutation Leading to Haploinsufficiency in a Patient with a Predominantly Antibody Deficiency. Journal of clinical immunology 11 32813180
2019 A Novel Monoallelic Nonsense Mutation in the NFKB2 Gene Does Not Cause a Clinical Manifestation. Frontiers in genetics 10 30863427
2018 TNFα-Induced Expression of Transport Protein Genes in HUVEC Cells Is Associated with Enhanced Expression of Transcription Factor Genes RELB and NFKB2 of the Non-Canonical NF-κB Pathway. Bulletin of experimental biology and medicine 10 29658079
1999 Genomic organization and chromosomal mapping of mouse nuclear factor kappa B 2 (NFKB2). Immunogenetics 10 10398801
2025 TRAIL induces cytokine production via the NFkB2 pathway promoting neutrophil chemotaxis and neutrophil-mediated immune-suppression in triple negative breast cancer cells. Cancer letters 9 40187604
2017 Effects of dried tofu supplementation during interval walking training on the methylation of the NFKB2 gene in the whole blood of older women. The journal of physiological sciences : JPS 9 29285709
2021 MiRNA-223-3p Affects Mantle Cell Lymphoma Development by Regulating the CHUK/NF-ƘB2 Signaling Pathway. OncoTargets and therapy 8 33688203
2019 Pathogenic NFKB2 variant in the ankyrin repeat domain (R635X) causes a variable antibody deficiency. Clinical immunology (Orlando, Fla.) 8 30953794
2017 Opposing roles of Nfkb2 gene products p100 and p52 in the regulation of breast cancer stem cells. Breast cancer research and treatment 8 28190248
2000 Normal structure of NFKB2, C-REL and BCL-3 gene loci in lymphoproliferative and myeloproliferative disorders. Leukemia & lymphoma 8 10830747
2022 Disseminated Coccidioidomycosis as the First Presentation of a C-Terminal NFKB2 Pathogenic Variant: A Case Report and Review of the Literature. The Pediatric infectious disease journal 7 34609106
2018 Early B cell developmental impairment with progressive B cell deficiency in NFKB2 mutated CVID disease without autoimmunity. Clinical immunology (Orlando, Fla.) 7 30500415
2022 Altered mRNA Expression of NFKB1 and NFKB2 Genes in Penile Lichen Sclerosus, Penile Cancer and Zoon Balanitis. Journal of clinical medicine 6 36555871
2019 ECCR1 and NFKB2 Polymorphisms as Potential Biomarkers of Non-small Cell Lung Cancer in a Polish Population. Anticancer research 6 31177178
2018 Analysis of NFKB2‑mediated regulation of mechanisms underlying the development of Hodgkin's lymphoma. Molecular medicine reports 6 29693141
2003 Refined physical map of the human PAX2/HOX11/NFKB2 cancer gene region at 10q24 and relocalization of the HPV6AI1 viral integration site to 14q13.3-q21.1. BMC genomics 6 12697057
2024 Type-Specific Impacts of Protein Defects in Pathogenic NFKB2 Variants: Novel Clinical Findings From 138 Patients. The journal of allergy and clinical immunology. In practice 5 39447838
1998 Interleukin-1 increases expression of the LYT-10 (NFkappaB2) proto-oncogene/transcription factor in renal cell carcinoma lines. The Journal of laboratory and clinical medicine 5 9523851
2025 Se-methylselenocysteine inhibits inflammatory response in an LPS-stimulated chicken HD11 macrophage-like cell model through the NFKB2 pathway. Frontiers in veterinary science 4 39846017
2024 Modeling corticotroph deficiency with pituitary organoids supports the functional role of NFKB2 in human pituitary differentiation. eLife 4 39607428
2019 Central Diabetes Insipidus in a Patient With NFKB2 Mutation: Expanding the Endocrine Phenotype in DAVID Syndrome. The Journal of clinical endocrinology and metabolism 4 31150062
2024 TRAIL-induced cytokine production via NFKB2 pathway promotes neutrophil chemotaxis and immune suppression in triple negative breast cancers. bioRxiv : the preprint server for biology 3 39091795
2024 A Novel Heterozygous NFKB2 Variant in a Multiplex Family with Common Variable Immune Deficiency and Autoantibodies Against Type I IFNs. Journal of clinical immunology 3 39579251
2021 Important role of Nfkb2 in the KrasG12D-driven carcinogenesis in the pancreas. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 3 33824054
1994 Isolation of a cDNA encoding the chicken p50B/p97 (Lyt-10) transcription factor. Gene 3 7510259
2025 A dataset on NFKB1/NFKB2 knockout Jurkat cells and primary CD4+ T cells generated by CRISPR/Cas9 mediated gene disruption. Data in brief 2 40027254
2024 Effects of high-pressure-processed rice intake during interval walking training on glycemic control and NFKB2 gene methylation in hyperglycemic older people. European journal of nutrition 2 39589533
2023 Case Report: Mycosis fungoides as an exclusive manifestation of common variable immunodeficiency in a family with a NFKB2 gene mutation. Frontiers in oncology 2 37781189
2022 Nfkb2 deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa. American journal of physiology. Gastrointestinal and liver physiology 2 35916405
2025 Intrinsic functional defects in B cells of patients with NFKB2 mutations. Clinical and experimental immunology 1 39405181
2025 Genetic and Functional Dissection of the NFKB2 Gene: Implications for Milk Fatty Acid Biosynthesis in Dairy Cattle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 40590069
2026 PLK1 stabilizes β-catenin to drive colorectal carcinogenesis through NFKB2-mediated transcriptional activation of USP2a and site-specific phosphorylation. Theranostics 0 41608586
2026 B3GNT3 facilitates NFKB2 processing and non-canonical NF-κB activation to drive lung adenocarcinoma progression. Cellular oncology (Dordrecht, Netherlands) 0 41838238
2025 Case report: novel NFKB2 variant associated with pediatric eosinophilic granulomatosis with polyangiitis (EGPA) in the COVID-19 pandemic. Pediatric rheumatology online journal 0 40165201
2025 Single-Cell Transcriptomic Analysis Highlights the Impact of NFKB2-Mediated MIF-CD44 Signaling Axis in Endometrioid Endometrial Cancer. International journal of women's health 0 41040843
2020 Correction to: A Nonsense N -Terminus NFKB2 Mutation Leading to Haploinsufficiency in a Patient with a Predominantly Antibody Deficiency. Journal of clinical immunology 0 32901356
2017 Erratum: NFKB2 mutation in common variable immunodeficiency and isolated adrenocorticotropic hormone deficiency: A case report and review of literature: Erratum. Medicine 0 31305727

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