NFKB2

Summary

NFKB2 (nuclear factor kappa B subunit 2, HGNC:7795) is a protein-coding gene on chromosome 10q24.32, encoding Nuclear factor NF-kappa-B p100 subunit (Q00653). NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cel….

This gene encodes a subunit of the transcription factor complex nuclear factor-kappa-B (NFkB). The NFkB complex is expressed in numerous cell types and functions as a central activator of genes involved in inflammation and immune function. The protein encoded by this gene can function as both a transcriptional activator or repressor depending on its dimerization partner. The p100 full-length protein is co-translationally processed into a p52 active form. Chromosomal rearrangements and translocations of this locus have been observed in B cell lymphomas, some of which may result in the formation of fusion proteins. There is a pseudogene for this gene on chromosome 18. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4791 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency, common variable, 10 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 751 total — 9 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 57
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Transcription factor: yes — 81 downstream targets (CollecTRI)
• MANE Select transcript: NM_001322934

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7795
Approved symbol	NFKB2
Name	nuclear factor kappa B subunit 2
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	LYT-10, p52, p105, NF-kB2, p49/p100
Ensembl gene	ENSG00000077150
Ensembl biotype	protein_coding
OMIM	164012
Entrez	4791

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 21 protein_coding, 10 retained_intron, 5 protein_coding_CDS_not_defined

ENST00000189444, ENST00000336486, ENST00000369966, ENST00000428099, ENST00000467116, ENST00000471698, ENST00000473400, ENST00000601386, ENST00000651907, ENST00000652277, ENST00000661543, ENST00000697881, ENST00000697882, ENST00000697883, ENST00000697884, ENST00000697916, ENST00000697917, ENST00000697918, ENST00000697919, ENST00000697920, ENST00000901568, ENST00000901569, ENST00000901570, ENST00000901571, ENST00000901572, ENST00000901573, ENST00000901574, ENST00000901575, ENST00000901576, ENST00000922218, ENST00000941742, ENST00000941743, ENST00000941744, ENST00000941745, ENST00000941746, ENST00000941747

RefSeq mRNA: 6 — MANE Select: NM_001322934 NM_001077494, NM_001261403, NM_001288724, NM_001322934, NM_001322935, NM_002502

CCDS: CCDS41564, CCDS41565

Canonical transcript exons

ENST00000661543 — 23 exons

Exon	Start	End
ENSE00000722730	102400080	102400194
ENSE00000722731	102400278	102400491
ENSE00000722732	102400655	102400824
ENSE00000722733	102400947	102401049
ENSE00000722734	102401180	102401331
ENSE00000722737	102401449	102401518
ENSE00000722739	102401745	102401917
ENSE00000722741	102402048	102402159
ENSE00001192799	102402252	102402524
ENSE00003507668	102396904	102397055
ENSE00003522392	102396725	102396823
ENSE00003544006	102398739	102398864
ENSE00003551043	102397981	102398085
ENSE00003559885	102396253	102396334
ENSE00003596816	102396449	102396489
ENSE00003607334	102398212	102398297
ENSE00003607610	102398385	102398523
ENSE00003631765	102399288	102399497
ENSE00003639580	102399577	102399718
ENSE00003666953	102397527	102397685
ENSE00003683065	102397302	102397408
ENSE00003848238	102395705	102395796
ENSE00003972019	102395888	102395980

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 96.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.8196 / max 3095.8935, expressed in 1817 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106700	18.8897	1791
106701	16.9431	1559
106696	16.1576	1566
106702	3.6732	486
106699	2.0646	1287
106697	0.8385	167
106703	0.7394	204
106710	0.2493	118
106709	0.1023	51
106708	0.0834	32

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.14	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.42	gold quality
spleen	UBERON:0002106	94.24	gold quality
lower esophagus mucosa	UBERON:0035834	94.19	gold quality
colonic epithelium	UBERON:0000397	93.42	gold quality
monocyte	CL:0000576	92.27	gold quality
lymph node	UBERON:0000029	92.05	gold quality
left uterine tube	UBERON:0001303	92.05	gold quality
upper lobe of left lung	UBERON:0008952	92.04	gold quality
gall bladder	UBERON:0002110	92.02	gold quality
sural nerve	UBERON:0015488	91.98	gold quality
omental fat pad	UBERON:0010414	91.81	gold quality
metanephros cortex	UBERON:0010533	91.80	gold quality
peritoneum	UBERON:0002358	91.72	gold quality
leukocyte	CL:0000738	91.67	gold quality
mononuclear cell	CL:0000842	91.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.47	gold quality
body of uterus	UBERON:0009853	91.30	gold quality
cartilage tissue	UBERON:0002418	91.25	gold quality
lower esophagus	UBERON:0013473	91.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.76	gold quality
endocervix	UBERON:0000458	90.75	gold quality
body of stomach	UBERON:0001161	90.52	gold quality
upper lobe of lung	UBERON:0008948	90.50	gold quality
sigmoid colon	UBERON:0001159	90.49	gold quality
apex of heart	UBERON:0002098	90.28	gold quality
minor salivary gland	UBERON:0001830	90.16	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.15	gold quality
right lobe of liver	UBERON:0001114	90.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.62

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

81 targets.

Target	Regulation
AIRE	Activation
AKR1B1	Activation
AP1
AQP2
AR
B2M	Unknown
BCL2	Unknown
BCL2L1	Activation
CCL19	Activation
CCL20	Activation
CCL21	Activation
CCL22	Repression
CCL5	Activation
CCND1	Unknown
CCND2	Activation
CD2
CD28
CD40
CD44
CD99
CDK6	Activation
CDKN1A
CHUK
CR2	Unknown
CRH
CSF2	Activation
CXCL13	Activation
CXCL8	Activation
DAPK1	Unknown
DMP1

JASPAR motifs

Motif	Name	Family
MA0778.1	NFKB2	NF-kappaB-related factors
MA0778.2	NFKB2	NF-kappaB-related factors

JASPAR matrix evidence (PMIDs): PMID:20066093

Upstream regulators (CollecTRI, top): AIP, ATF3, E2F4, FOXC1, JUN, NFKB1, NFKB2, NFKB, NOTCH1, PLCG2, RBPJ, REL, RELA, SP1, STAT2, TP53

miRNA regulators (miRDB)

22 targeting NFKB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-609	99.82	64.26	505
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-4259	95.68	65.25	582
HSA-MIR-1914-3P	95.07	63.37	762

Literature-anchored findings (GeneRIF, showing 40)

• Genetic evidence for the essential role of beta-transducin repeat-containing protein in the inducible processing of NF-kappa B2/p100 (PMID:11994270)
• interaction with S9 19S proteasome subunit (PMID:12185077)
• BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells (PMID:12352969)
• NF-kappa B2 p100 has I kappa B-independent apoptotic activity and a unique tumour suppressor role (PMID:12389034)
• LT-beta receptor agonists and LPS induce NF-kappaB/p100 processing to p52 at the level of the ribosome. (PMID:12524526)
• p52 NF-kappaB subunit associates with histone deacetylase 1 when p53 represses cyclin D1 transcription through down regulation of Bcl-3 (PMID:12808109)
• p50 and p52 homodimers can transactivate the bcl-2 promoter through association with Bcl-3; in breast cancer and leukemic cells (CLL), high NF-kappaB2/p100 expression was associated with high Bcl-2 expression (PMID:12835724)
• RelB has an effect on p100 processing, which is possibly regulated in a signal-dependent manner (PMID:12874295)
• Constitutive processing of C-terminal truncation mutants of p100 is associated with their active nuclear translocation. Mutation of the nuclear localization signal (NLS) of p100 abolishes its processing. (PMID:12894228)
• p100HB is a new mutant form of p100/NF-kappa B2 associated with deregulated NF-kappa B/Rel functions (PMID:12927781)
• LMP1 activation of these two NF-kappa B pathways, NFKB2 and I kappa B alpha, is shown here to require distinct regions of the LMP1 C-terminal cytoplasmic tail. (PMID:14532284)
• The mechanism of processing of the NFKB2 precursor is regulated by a unique pathway. (PMID:14676825)
• Induction of p100 processing by NF-kappaB-inducing kinase involves docking IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation (PMID:15140882)
• beta-transducin repeat-containing protein-dependent and -independent mechanisms contribute to Tax-deregulated p100 processing (PMID:15310758)
• the mechanism by which the different sequences within p100 work in concert to regulate its processing (PMID:15485830)
• IkappaB kinase alpha has an essential role in the constitutive processing of NF-kappaB2 p100 (PMID:15677466)
• Enhanced expression of NF-kappaB2/p52 and RelB-containing NF-kappaB DNA-binding activity in Epstein-Barr virus-negative Reed Sternberg cells. (PMID:15782119)
• (p52)2/Bcl-3P ternary complex, which is specifically induced in CD30-stimulated anaplastic large cell lymphoma, can modulate expression of apoptosis-related genes regulated by NF-kappaB. (PMID:16108830)
• studies define one important mechanism of NF-kappaB-inducing kinase (NIK) regulation and the central role of NIK stabilization in the induction of NF-kappaB2 precursor protein p100 processing (PMID:16223731)
• mutants of p53 may induce loss of drug sensitivity is via the NF-kappaB2 pathway (PMID:16260623)
• These data suggest that p100 processing involves its phosphorylation at specific terminal serines, which form a binding site for beta-TrCP thereby regulating p100 ubiquitination. (PMID:16303288)
• Stat3-mediated p100 processing to p52 requires activation of Stat3 by the acetyltransferase activity of cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300 (PMID:16651533)
• Data demonstrate an important role of NF-kappaB-1 and -2 pathways in mediating resistance to apoptosis and distinctive antiapoptotic downstream target gene profiles responsible for this effect. (PMID:16751281)
• HBx and NF-kappaB2/BCL3 mediated-cyclin D1 up-regulation might play an important role in the HBx-mediated HCC development and progression (PMID:16940298)
• p52 can regulate p53 function and influence p53-regulated decision-making following DNA damage and oncogene activation. (PMID:16990795)
• Novel interactions reveal of IKKepsilon in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65 are reported. (PMID:17003035)
• We herein report that STP-A11 activates non-canonical NF-kappaB pathway, resulting in p100 processing to p52. (PMID:17028057)
• Monarch-1 inhibits CD40-mediated activation of NFKB and processing of NFKB2 to p52. This inhibition stems from the ability of Monarch-1 to associate with and induce proteasome-mediated degradation of NF-kappaB inducing kinase. (PMID:17237370)
• Study reports that androgenic stimulation of LNCaP cells with the androgen analogue R1881 appears to positively regulate the non-canonical NF-kappaB pathway as p52 accumulates both in the cytoplasm and nucleus after 48-72 h of stimulation. (PMID:17292587)
• C-terminally truncated NF-kappaB2 precursors are endoproteolytically processed at kappaB-containing promoters (PMID:17363471)
• cell adhesion-mediated proteolysis of the NF-kappaB precursor, p100 (NF-kappaB2) resulted in the generation of active p52, which translocated to the nucleus in complex with p65 and RelB (PMID:17476277)
• NF-kappaB2/p100 acts as a late-acting negative-feedback signaling molecule in the TCR-mediated NF-kappaB pathway. (PMID:17548614)
• activation of NF-kappaB2/p100 plays a crucial role in the Tax1-mediated transformation of T cells (PMID:17715223)
• The findings demonstrate a key role for NF-kappaB2 in the regulation of RelA activation and suggest overlap in the function of NF-kappaB members in canonical and noncanonical pathway signaling. (PMID:18025196)
• demonstrated that human hepatocellular carcinomas almost universally overexpress Bcl-3 and preferentially express nuclear p52 and p50, with little evidence of p65 activation (PMID:18025803)
• These unique protein-protein contacts explain why RelB prefers p52 as its dimeric partner for transcriptional activity and is retained in the cytoplasm as an inhibited complex by p100. (PMID:18321863)
• NF-kappaB2 gene rearrangement may be a factor in the constitutive activation of NF-kappaB in ATL, and thereby playing a role in the ATL pathogenesis. (PMID:18377428)
• NFkappaB2 gene duplication is associated with fetal pyelectasis in partial trisomy 10q (10q24.1 –> qter). (PMID:18383001)
• RIG-1 - MAVS interacts with cytoplasmic 100-kDa NF-kappa B2 complexes via a novel retinoic acid-inducible gene-I - NF- kappa B-inducing kinase signaling pathway (PMID:18550535)
• Overexpression of NF-kappaB2/p52 protects androgen sensitive human prostate cancer cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. (PMID:18781579)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nfkb2	ENSMUSG00000025225
rattus_norvegicus	Nfkb2	ENSRNOG00000019311
drosophila_melanogaster	Dif	FBGN0011274
drosophila_melanogaster	dl	FBGN0260632

Paralogs (4): RELB (ENSG00000104856), NFKB1 (ENSG00000109320), REL (ENSG00000162924), RELA (ENSG00000173039)

Protein

Protein identifiers

Nuclear factor NF-kappa-B p100 subunit — Q00653 (reviewed: Q00653)

Alternative names: DNA-binding factor KBF2, H2TF1, Lymphocyte translocation chromosome 10 protein, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, Oncogene Lyt-10

All UniProt accessions (1): Q00653

UniProt curated annotations — full annotation on UniProt →

Function. NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5’-GGRNNYYCC-3’, located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer.

Subunit / interactions. Component of the NF-kappa-B RelB-p52 complex. Homodimer; component of the NF-kappa-B p52-p52 complex. Component of the NF-kappa-B p65-p52 complex. Component of the NF-kappa-B p52-c-Rel complex. NFKB2/p52 interacts with NFKBIE. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Directly interacts with MEN1.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p52 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing. Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing. Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain. Ubiquitinated by TRIM55; leading to processing by VCP and subsequent ubiquitin-dependent protein degradation by the proteasome.

Disease relevance. A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant. A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT). In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions. Immunodeficiency, common variable, 10 (CVID10) [MIM:615577] A primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B-cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation. The glycine-rich region (GRR) appears to be a critical element in the generation of p52.

Isoforms (3)

UniProt ID	Names	Canonical?
Q00653-1	1, p100	yes
Q00653-3	3, p49
Q00653-4	4

RefSeq proteins (6): NP_001070962, NP_001248332, NP_001275653, NP_001309863, NP_001309864, NP_002493 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000451	NFkB/Dor	Family
IPR000488	Death_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR002909	IPT_dom	Domain
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR011539	RHD_DNA_bind_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR030492	RHD_CS	Conserved_site
IPR030497	NFkB_p100_RHD_N	Domain
IPR032397	RHD_dimer	Domain
IPR033926	IPT_NFkappaB	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037059	RHD_DNA_bind_dom_sf	Homologous_superfamily

Pfam: PF00023, PF00531, PF00554, PF12796, PF16179

UniProt features (133 total): strand 29, helix 27, turn 13, sequence conflict 11, sequence variant 10, mutagenesis site 10, modified residue 9, repeat 7, region of interest 4, splice variant 3, chain 2, domain 2, compositionally biased region 2, site 2, short sequence motif 1, cross-link 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
1A3Q	X-RAY DIFFRACTION	2.1
8G8S	X-RAY DIFFRACTION	2.1
8G8Q	X-RAY DIFFRACTION	2.6
5ZMC	X-RAY DIFFRACTION	2.99
7CLI	X-RAY DIFFRACTION	3
7W7L	X-RAY DIFFRACTION	3
3DO7	X-RAY DIFFRACTION	3.05
7VUQ	X-RAY DIFFRACTION	3.1
4OT9	X-RAY DIFFRACTION	3.35
7VUP	X-RAY DIFFRACTION	3.4
2D96	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00653-F1	75.94	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 454–455 (cleavage (when cotranslationally processed)); 490–491 (breakpoint for translocation to form nfkb2-igha1 oncogene)

Post-translational modifications (10): 23, 161, 429, 713, 715, 717, 812, 866, 870, 855

Mutagenesis-validated functional residues (10):

Position	Phenotype
247–249	two-fold reduction in heterodimerization with rela.
399	no change in cleavage rate or products.
404	no change in cleavage rate or products.
405	no change in cleavage rate or products.
406	no change in cleavage rate or products.
713	loss of phosphorylation; when associated with a-715 and a-717.
715	loss of phosphorylation; when associated with g-713 and a-717.
717	loss of phosphorylation; when associated with g-713 and a-715.
866	decrease in map3k14-induced phosphorylation; no inducible processing occurs; when associated with a-869.
870	decrease in map3k14-induced phosphorylation; no inducible processing occurs; when associated with a-865.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-1810476	RIP-mediated NFkB activation via ZBP1
R-HSA-3134963	DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-448706	Interleukin-1 processing
R-HSA-4755510	SUMOylation of immune response proteins
R-HSA-5603029	IkBA variant leads to EDA-ID
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5676590	NIK–>noncanonical NF-kB signaling
R-HSA-844456	The NLRP3 inflammasome
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-9909649	Regulation of PD-L1(CD274) transcription

MSigDB gene sets: 505 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, CREL_01, MYAATNNNNNNNGGC_UNKNOWN, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_THE_NLRP3_INFLAMMASOME, GOBP_RESPONSE_TO_PEPTIDE, DORN_ADENOVIRUS_INFECTION_12HR_UP, REACTOME_INFLAMMASOMES, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, KEGG_MAPK_SIGNALING_PATHWAY, MODULE_522, MODULE_45

GO Biological Process (13): follicular dendritic cell differentiation (GO:0002268), germinal center formation (GO:0002467), regulation of DNA-templated transcription (GO:0006355), canonical NF-kappaB signal transduction (GO:0007249), extracellular matrix organization (GO:0030198), response to lipopolysaccharide (GO:0032496), response to cytokine (GO:0034097), non-canonical NF-kappaB signal transduction (GO:0038061), positive regulation of transcription by RNA polymerase II (GO:0045944), rhythmic process (GO:0048511), spleen development (GO:0048536), signal transduction (GO:0007165), intracellular signaling cassette (GO:0141124)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), Bcl3/NF-kappaB2 complex (GO:0033257), I-kappaB/NF-kappaB complex (GO:0033256)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
ZBP1(DAI) mediated induction of type I IFNs	1
Cytosolic sensors of pathogen-associated DNA	1
Chromatin modifying enzymes	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
Toll Like Receptor 3 (TLR3) Cascade	1
Interleukin-1 signaling	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
MyD88 cascade initiated on plasma membrane	1
Interleukin-1 family signaling	1
SUMO E3 ligases SUMOylate target proteins	1
Diseases associated with the TLR signaling cascade	1
CLEC7A (Dectin-1) signaling	1
TNFR2 non-canonical NF-kB pathway	1
Inflammasomes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
intracellular signaling cassette	2
regulation of transcription by RNA polymerase II	2
follicular dendritic cell activation	1
cell differentiation	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
anatomical structure formation involved in morphogenesis	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
extracellular structure organization	1
external encapsulating structure organization	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
response to peptide	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
biological_process	1
hematopoietic or lymphoid organ development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signal transduction	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1

Protein interactions and networks

STRING

3620 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFKB2	RELB	Q01201	988
NFKB2	REL	Q04864	987
NFKB2	RELA	Q04206	987
NFKB2	BCL3	P20749	985
NFKB2	NFKB1	P19838	984
NFKB2	CHUK	O15111	923
NFKB2	IKBKB	O14920	870
NFKB2	LTBR	P36941	857
NFKB2	IKBKG	Q9Y6K9	849
NFKB2	TNFRSF13C	Q96RJ3	831
NFKB2	TNFSF13B	Q9Y275	797
NFKB2	CXCL8	P10145	779
NFKB2	LTB	P78370	777
NFKB2	MAP3K14	Q99558	770
NFKB2	CD40	P25942	767

IntAct

193 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
MAP3K8	NFKB1	psi-mi:“MI:0914”(association)	0.930
NFKB2	NFKB1	psi-mi:“MI:0915”(physical association)	0.820
NFKB2	NFKB1	psi-mi:“MI:0914”(association)	0.820
NFKBIB	NFKB1	psi-mi:“MI:0914”(association)	0.820
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
NFKB1	IKBKB	psi-mi:“MI:0914”(association)	0.770
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.760
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
RELB	NFKBIE	psi-mi:“MI:0914”(association)	0.670
REL	NFKBIE	psi-mi:“MI:0914”(association)	0.670
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
NFKBIB	CHUK	psi-mi:“MI:0914”(association)	0.670
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
RELA	NFKBIE	psi-mi:“MI:0914”(association)	0.620
NFKB1	NFKBIE	psi-mi:“MI:2364”(proximity)	0.600
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
ALOX5	DDHD2	psi-mi:“MI:0914”(association)	0.530
DEF6	NFKB2	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (228): NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-RNA), NFKB2 (Affinity Capture-RNA), NFKB2 (Affinity Capture-Western), NFKB2 (Biochemical Activity), NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), NFKB2 (Affinity Capture-MS), NFKB2 (Proximity Label-MS), NFKB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2MDK8, A0PJX2, A2ACG1, D3ZBP4, E2RDP2, F1MH07, O08644, O75038, O75064, O75636, P0C0K7, P0DPD7, P0DPE0, P0DPE1, P52824, Q00653, Q0IID2, Q1LWV7, Q3SYT1, Q3U1Y4, Q4KM32, Q4R380, Q5NCQ5, Q5RKI3, Q62137, Q684M2, Q68DD2, Q6ZSI9, Q86TL0, Q86XP0, Q8BGV9, Q8BX80, Q8C9V1, Q8NFF5, Q8NFI3, Q8R5G7, Q8TDZ2, Q8VDP3, Q8WWN8, Q91ZJ0

Diamond homologs: A2ARS0, B2RXR6, C9JTQ0, L7XCU0, L7XDS4, O15084, O75762, O89019, P25799, Q00653, Q18297, Q2TB02, Q3EC11, Q3KP44, Q3SX00, Q4JHE0, Q4ULZ2, Q502K3, Q505D1, Q5F478, Q5R8C8, Q5U464, Q5ZLC8, Q61982, Q6JAN1, Q6RI86, Q810B6, Q86W74, Q8BLD6, Q8BTI7, Q8N8A2, Q8NB46, Q8UVC3, Q94B55, Q9R172, Q9UM47, Q9WTK5, Q9Y283, O00221, O54910

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
MAP3K14	“up-regulates activity”	NFKB2	phosphorylation
RBX1	up-regulates	NFKB2	ubiquitination
BCL3	up-regulates	NFKB2	binding
BCL3	up-regulates	NFKB2
TP53	up-regulates	NFKB2	binding
NFKB2	“up-regulates activity”	RELB	binding
SCF-betaTRCP	“up-regulates activity”	NFKB2	ubiquitination
TSC22D3	“down-regulates activity”	NFKB2	binding
GSK3B	“down-regulates activity”	NFKB2	phosphorylation
NOTCH1	“up-regulates quantity by expression”	NFKB2	“transcriptional regulation”
RBPJ	“down-regulates quantity by repression”	NFKB2	“transcriptional regulation”
CHUK	“up-regulates activity”	NFKB2	phosphorylation
FBXW7	“down-regulates quantity by destabilization”	NFKB2	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	NFKB2	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 164 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
MAP3K8 (TPL2)-dependent MAPK1/3 activation	10	52.5×	8e-15
RIP-mediated NFkB activation via ZBP1	8	39.5×	1e-10
Eukaryotic Translation Initiation	15	34.0×	2e-18
Cap-dependent Translation Initiation	15	34.0×	2e-18
SARS-CoV-1 modulates host translation machinery	15	34.0×	2e-18
Eukaryotic Translation Elongation	16	32.8×	3e-19
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	15	30.0×	2e-17
Selenoamino acid metabolism	19	27.5×	3e-21

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	9	49.6×	2e-11
protein refolding	7	28.6×	6e-07
cytoplasmic translation	23	27.8×	3e-24
canonical NF-kappaB signal transduction	10	23.9×	2e-09
ribosomal small subunit biogenesis	13	19.4×	3e-11
activation of innate immune response	5	15.7×	1e-03
translation	23	15.4×	3e-18
tumor necrosis factor-mediated signaling pathway	7	15.1×	5e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — DLBCLNOS, PLMESO.

Clinical variants and AI predictions

ClinVar

751 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	7
Uncertain significance	331
Likely benign	335
Benign	32

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1409384	NM_001322934.2(NFKB2):c.2602_2605dup (p.Gly869fs)	Pathogenic
155764	NM_001322934.2(NFKB2):c.2556_2563del (p.Arg853fs)	Pathogenic
2915458	NM_001322934.2(NFKB2):c.2596_2597del (p.Ser866fs)	Pathogenic
620553	NM_001322934.2(NFKB2):c.937C>T (p.Arg313Ter)	Pathogenic
65385	NM_001322934.2(NFKB2):c.2557C>T (p.Arg853Ter)	Pathogenic
65386	NM_001322934.2(NFKB2):c.2564del (p.Lys855fs)	Pathogenic
827730	NM_001322934.2(NFKB2):c.1469+1G>T	Pathogenic
827731	NM_001322934.2(NFKB2):c.1903C>T (p.Arg635Ter)	Pathogenic
871139	NM_001322934.2(NFKB2):c.2611C>T (p.Gln871Ter)	Pathogenic
2432214	NM_001322934.2(NFKB2):c.1359_1363dup (p.Gln455fs)	Likely pathogenic
2632365	NM_001322934.2(NFKB2):c.2173C>T (p.Arg725Ter)	Likely pathogenic
3340687	NM_001322934.2(NFKB2):c.1416_1417del (p.Leu473fs)	Likely pathogenic
421588	NM_001322934.2(NFKB2):c.2609G>A (p.Ser870Asn)	Likely pathogenic
572397	NM_001322934.2(NFKB2):c.2576_2580del (p.Thr859fs)	Likely pathogenic
935289	NM_001322934.2(NFKB2):c.2595_2596del (p.Asp865fs)	Likely pathogenic
982877	NM_001322934.2(NFKB2):c.104-1G>C	Likely pathogenic

SpliceAI

3401 predictions. Top by Δscore:

Variant	Effect	Δscore
10:102396445:CCA:C	acceptor_loss	1.0000
10:102396447:A:AG	acceptor_gain	1.0000
10:102396447:AGCT:A	acceptor_gain	1.0000
10:102396447:AGCTG:A	acceptor_loss	1.0000
10:102396448:G:GT	acceptor_gain	1.0000
10:102396448:GC:G	acceptor_gain	1.0000
10:102396448:GCT:G	acceptor_gain	1.0000
10:102396448:GCTG:G	acceptor_gain	1.0000
10:102396448:GCTGA:G	acceptor_gain	1.0000
10:102396486:GCAG:G	donor_gain	1.0000
10:102396488:AGG:A	donor_loss	1.0000
10:102396490:GTGA:G	donor_loss	1.0000
10:102396714:T:TA	acceptor_gain	1.0000
10:102396724:GAGA:G	acceptor_gain	1.0000
10:102396820:CAAGG:C	donor_loss	1.0000
10:102396821:AAGG:A	donor_loss	1.0000
10:102396822:AGG:A	donor_loss	1.0000
10:102396901:TAGAT:T	acceptor_loss	1.0000
10:102396902:A:AG	acceptor_gain	1.0000
10:102396903:G:GG	acceptor_gain	1.0000
10:102396903:GATCT:G	acceptor_gain	1.0000
10:102397051:GCCCA:G	donor_gain	1.0000
10:102397056:G:GG	donor_gain	1.0000
10:102397399:GGCCT:G	donor_gain	1.0000
10:102397525:A:AG	acceptor_gain	1.0000
10:102397526:G:GG	acceptor_gain	1.0000
10:102397976:CATA:C	acceptor_loss	1.0000
10:102397978:TA:T	acceptor_loss	1.0000
10:102397979:A:AG	acceptor_gain	1.0000
10:102397980:G:GC	acceptor_gain	1.0000

AlphaMissense

5765 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:102396482:C:A	P46H	1.000
10:102396731:T:C	F51L	1.000
10:102396732:T:C	F51S	1.000
10:102396733:C:A	F51L	1.000
10:102396733:C:G	F51L	1.000
10:102396737:T:C	F53L	1.000
10:102396738:T:C	F53S	1.000
10:102396738:T:G	F53C	1.000
10:102396739:T:A	F53L	1.000
10:102396739:T:G	F53L	1.000
10:102396779:G:C	G67R	1.000
10:102396780:G:A	G67D	1.000
10:102396812:C:T	P78S	1.000
10:102396813:C:A	P78H	1.000
10:102396813:C:G	P78R	1.000
10:102396819:T:A	V80D	1.000
10:102396926:C:A	A89D	1.000
10:102396944:T:A	L95Q	1.000
10:102396944:T:C	L95P	1.000
10:102396981:C:A	H107Q	1.000
10:102396981:C:G	H107Q	1.000
10:102396986:T:A	L109Q	1.000
10:102397304:T:C	F133S	1.000
10:102397313:T:C	L136P	1.000
10:102397324:C:G	H140D	1.000
10:102397596:G:C	R191P	1.000
10:102397599:T:A	L192Q	1.000
10:102397599:T:C	L192P	1.000
10:102397602:G:C	R193P	1.000
10:102397604:T:C	F194L	1.000

dbSNP variants (sampled 300 via entrez): RS1000302344 (10:102392566 C>T), RS1000805666 (10:102392155 T>C), RS1001578971 (10:102399770 G>A), RS1001922617 (10:102398205 C>G,T), RS1002569529 (10:102402438 A>G), RS1002695480 (10:102395492 C>G), RS1003159554 (10:102395206 A>C,G), RS1003223323 (10:102394591 C>T), RS1003575177 (10:102400905 G>A), RS1003750008 (10:102393970 G>C,T), RS1003904089 (10:102402009 C>T), RS1003930635 (10:102395111 G>A,C,T), RS1004053694 (10:102401175 C>G,T), RS1004599977 (10:102395514 G>A), RS1004758695 (10:102395612 G>C)

Disease associations

OMIM: gene MIM:164012 | disease phenotypes: MIM:615577, MIM:607594

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency, common variable, 10	Strong	Autosomal dominant
common variable immunodeficiency	Supportive	Autosomal dominant
deficiency in anterior pituitary function - variable immunodeficiency syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency, common variable, 10	Definitive	AD

Mondo (5): immunodeficiency, common variable, 10 (MONDO:0014260), common variable immunodeficiency (MONDO:0015517), immunodeficiency, common variable, 1 (MONDO:0011864), hereditary breast ovarian cancer syndrome (MONDO:0003582), deficiency in anterior pituitary function - variable immunodeficiency syndrome (MONDO:0017407)

Orphanet (3): OBSOLETE: Common variable immunodeficiency (Orphanet:1572), Late-onset combined immunodeficiency due to ICOS deficiency (Orphanet:695183), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000403	Recurrent otitis media
HP:0000651	Diplopia
HP:0000824	Decreased response to growth hormone stimulation test
HP:0001045	Vitiligo
HP:0001263	Global developmental delay
HP:0001325	Hypoglycemic coma
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001943	Hypoglycemia
HP:0001973	Autoimmune thrombocytopenia
HP:0001988	Recurrent hypoglycemia
HP:0002021	Pyloric stenosis
HP:0002099	Asthma
HP:0002110	Bronchiectasis
HP:0002121	Generalized non-motor (absence) seizure
HP:0002153	Hyperkalemia
HP:0002615	Hypotension
HP:0002720	Decreased circulating IgA concentration
HP:0002788	Recurrent upper respiratory tract infections
HP:0002837	Recurrent bronchitis
HP:0002850	Decreased circulating total IgM
HP:0002902	Hyponatremia
HP:0002920	Decreased circulating ACTH concentration
HP:0003765	Psoriasiform dermatitis
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0004315	Decreased circulating IgG concentration
HP:0004332	Abnormal lymphocyte morphology
HP:0004429	Recurrent viral infections
HP:0005215	Frequent Giardia lamblia infestation

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003045_28	Ulcerative colitis	3.000000e-07
GCST005956_50	Waist-to-hip ratio adjusted for BMI	8.000000e-06
GCST005958_15	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-06
GCST005962_36	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST009391_921	Metabolite levels	9.000000e-07
GCST010002_298	Refractive error	3.000000e-22

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010443	triacylglycerol 58:9 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D017074	Common Variable Immunodeficiency	C20.673.330
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094258 (PROTEIN COMPLEX GROUP), CHEMBL3003 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 562,806 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL15870	INDOPROFEN	4	22,854
CHEMBL2348780	VAMOROLONE	4	151
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL384467	DEXAMETHASONE	4	279,102
CHEMBL421	SULFASALAZINE	4	73,629
CHEMBL140	CURCUMIN	3	93,882
CHEMBL165	RESVERATROL	3	60,144
CHEMBL2141296	IXAZOMIB	3	6,022
CHEMBL4288984	WITHANOLIDE D	3	60
CHEMBL463763	TRIPTOLIDE	3	258
CHEMBL128988	FRENTIZOLE	2	189
CHEMBL15192	LAPACHONE	2	589
CHEMBL417799	SANGUINARIUM	2	8,822
CHEMBL129857	AS-602868	1	93
CHEMBL517080	WITHAFERIN A	1	3,891

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1056890	NFKB2, PSD		0.00	0
rs12772374	NFKB2		0.00	0
rs12769316	NFKB2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — NF-kappa B TF proteins

ChEMBL bioactivities

981 potent at pChembl≥5 of 1230 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.60	IC50	0.025	nM	CHEMBL5080827
10.37	Kd	0.043	nM	CHEMBL329415
10.22	IC50	0.06	nM	LIPOXIN A4
9.30	IC50	0.5	nM	DEXAMETHASONE
8.72	IC50	1.9	nM	CHEMBL5532458
8.52	IC50	3	nM	CHEMBL337665
8.21	IC50	6.2	nM	IXAZOMIB
8.10	IC50	8	nM	AS-602868
8.05	IC50	9	nM	CHEMBL3218828
8.05	IC50	9	nM	CHEMBL3218834
8.05	IC50	9	nM	CHEMBL3218836
8.05	EC50	9	nM	CHEMBL5279887
8.01	IC50	9.7	nM	BORTEZOMIB
8.00	IC50	10	nM	CHEMBL3218835
8.00	IC50	10	nM	TRIPTOLIDE
7.92	IC50	12	nM	CHEMBL3218824
7.92	IC50	12	nM	CHEMBL3218837
7.82	IC50	15	nM	CHEMBL4850374
7.77	IC50	17	nM	CHEMBL3218833
7.75	IC50	18	nM	CHEMBL3218831
7.70	IC50	20	nM	CHEMBL43549
7.66	IC50	22	nM	CHEMBL3218826
7.64	IC50	23	nM	CHEMBL3218823
7.60	IC50	25	nM	CHEMBL3218827
7.52	IC50	30	nM	CHEMBL552054
7.50	IC50	32	nM	CHEMBL3218825
7.50	IC50	32	nM	CHEMBL4848017
7.46	IC50	35	nM	CHEMBL85822
7.44	IC50	36	nM	WITHANOLIDE D
7.42	IC50	38	nM	CHEMBL3218829
7.41	IC50	39	nM	CHEMBL3218832
7.39	IC50	41	nM	CHEMBL4852942
7.35	IC50	45	nM	CHEMBL1269181
7.35	IC50	45	nM	CHEMBL86615
7.33	IC50	47	nM	WITHAFERIN A
7.30	IC50	50	nM	CHEMBL336546
7.30	IC50	50	nM	CHEMBL132495
7.30	IC50	50	nM	CHEMBL4869263
7.28	IC50	53	nM	CHEMBL3218843
7.26	IC50	55	nM	CHEMBL3234472
7.25	IC50	56	nM	CHEMBL3234471
7.23	IC50	59	nM	CHEMBL4859862
7.23	EC50	59	nM	CHEMBL1322308
7.23	EC50	59	nM	CHEMBL1384554
7.23	EC50	59	nM	CHEMBL3197844
7.23	EC50	59	nM	CHEMBL1452672
7.21	IC50	62	nM	CHEMBL3218821
7.21	IC50	62	nM	CHEMBL3218822
7.21	EC50	62	nM	CHEMBL1505937
7.20	IC50	63	nM	CHEMBL4857813

PubChem BioAssay actives

207 with measured affinity, of 1385 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
methyl (E,5S,6R)-5,6-dihydroxy-8-[3-[(1R)-1-hydroxyhexyl]quinoxalin-2-yl]oct-7-enoate	1817450: Inhibition of LPS-induced NF-kappaB activation in human THP-1 monocytes expressing luciferase gene pretreated for 30 mins followed by LPS stimulation and measured after 24 hrs by bioluminescence analysis	ic50	<0.0001	uM
methyl (E,5S,6R)-5,6-dihydroxy-8-[3-[(1S)-1-hydroxyhexyl]quinoxalin-2-yl]oct-7-enoate	1817450: Inhibition of LPS-induced NF-kappaB activation in human THP-1 monocytes expressing luciferase gene pretreated for 30 mins followed by LPS stimulation and measured after 24 hrs by bioluminescence analysis	ic50	<0.0001	uM
(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-trihydroxyicosa-7,9,11,13-tetraenoic acid	1817450: Inhibition of LPS-induced NF-kappaB activation in human THP-1 monocytes expressing luciferase gene pretreated for 30 mins followed by LPS stimulation and measured after 24 hrs by bioluminescence analysis	ic50	0.0001	uM
Dexamethasone	2131645: Inhibition of NF-kappaB (unknown origin)	ic50	0.0005	uM
N-methyl-N-[3-methyl-3-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]oxycyclobutyl]prop-2-enamide	2064208: Inhibition of NF-kappaB activation in human TMD8 cells assessed as reduction in nucleus translocation	ic50	0.0019	uM
1-[(6-methoxy-2-thiophen-2-ylquinazolin-4-yl)amino]-3-methylpyrrole-2,5-dione	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0030	uM
1-[(5-methoxy-2-thiophen-2-ylquinazolin-4-yl)amino]-3-methylpyrrole-2,5-dione	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0080	uM
1-N-[2-(4-phenoxyphenyl)ethyl]phthalazine-1,7-diamine	1922378: Inhibition of NFkappaB in human Jurkat cells incubated for 30 mins by bright-glo luciferase assay	ec50	0.0090	uM
(1S,2S,4S,5S,7R,8R,9S,11S,13S)-8-hydroxy-1-methyl-7-propan-2-yl-3,6,10,16-tetraoxaheptacyclo[11.7.0.02,4.02,9.05,7.09,11.014,18]icos-14(18)-en-17-one	2075668: Inhibition of NF-kappaB (unknown origin)	ic50	0.0100	uM
(1S,2R,6S,7R,9R,11S,12S,15R,16S)-15-[(1S)-1-[(2R)-5-ethyl-4-methyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-6-hydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0150	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-2-ylpyrimidine-5-carboxylate	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0200	uM
(1’S,3’R,5’S,7’R,10’R,12’R,14’R,15’S,18’R,19’R,22’S,23’R)-10’,22’-dihydroxy-14’-(hydroxymethyl)-7’,18’-dimethyl-19’-(5-oxo-2H-furan-3-yl)spiro[1,3-thiazolidine-2,9’-4,6,11-trioxahexacyclo[12.11.0.03,12.05,10.015,23.018,22]pentacosane]-4-one	1142307: Inhibition of NF-kappaB transactivation in TNF-alpha-stimulated human K562 cells preincubated for 2 hrs followed by TNF-alpha challenge measured after 6 hrs by dual luciferase reporter gene assay	ic50	0.0300	uM
[(1S,2R,6S,7S,9R,11S,12S,15S,16S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-6-yl] acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0320	uM
ethyl 4-ethyl-2-[methyl-(3-methyl-2,5-dioxopyrrol-1-yl)amino]pyrimidine-5-carboxylate	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0350	uM
(1S,2R,6S,7R,9R,11S,12S,15S,16S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-6-hydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0360	uM
(1S,2R,6S,7R,9R,11R,12R,16R)-15-[(1R)-1-[(2R,4S)-4,5-dimethyl-6-oxooxan-2-yl]-1-hydroxyethyl]-6,12-dihydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadeca-4,14-dien-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0410	uM
ethyl 2-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-4-(5-methylthiophen-2-yl)pyrimidine-5-carboxylate	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0450	uM
(1S,2R,6S,7R,9R,11S,12S,15R,16S)-6-hydroxy-15-[(1S)-1-[(2R)-5-(hydroxymethyl)-4-methyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0470	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-chloro-4-methylpyrimidine-5-carboxamide	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0500	uM
[(1S,2R,6S,7S,9R,11R,12S,13R,15S,16S)-6-acetyloxy-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-13-yl] acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0500	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxamide	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0500	uM
[(2R)-2-[(1S)-1-[(1S,2R,6S,7S,9R,11S,12S,15R,16S)-6-acetyloxy-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-15-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0550	uM
[(1S,2R,6S,7S,9R,11S,12S,15R,16S)-15-[(1S)-1-[(2R)-5-(hydroxymethyl)-4-methyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-6-yl] acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0560	uM
[(1S,2R,6R,7S,9R,11S,12S,15S,16S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-6-yl] acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0590	uM
[(2R)-2-[(1S)-1-[(1S,2R,7R,9R,11S,12S,14S,15R,16S)-6-hydroxy-2,14,16-trimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-15-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0630	uM
(1S,4S,7S,10S,13R,16R)-21-hydroxy-7-[(4-methoxyphenyl)methyl]-2,4,8,10,13,31-hexamethyl-23-oxa-2,5,8,11,14,31-hexazatetracyclo[14.13.2.118,22.124,28]tritriaconta-18(33),19,21,24,26,28(32)-hexaene-3,6,9,12,15,30-hexone	1772488: Inhibition of NF-kB (unknown origin) expressed in HEK293T cells transfected with pTK-Renilla reporter preincubated for 6 hrs followed by addition of TNF-alpha and measured after 8 hrs by Dual luciferase reporter assay	ic50	0.0650	uM
Vamorolone	2075668: Inhibition of NF-kappaB (unknown origin)	ic50	0.0659	uM
[(2R)-2-[(1S)-1-[(1S,2R,6S,7R,9R,11S,12S,15R,16S)-6-hydroxy-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-15-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0700	uM
(1S,2R,7R,9R,11S,12S,15S,16S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-6-hydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0710	uM
(1S,2R,6S,7R,9R,11S,12S,14S,15R,16S)-15-[(1R)-1-[(2R,4S,5R)-4,5-dimethyl-6-oxooxan-2-yl]-1-hydroxyethyl]-6,14-dihydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0740	uM
[(2R)-2-[(1S)-1-[(1S,2R,5S,6S,7R,9R,11S,12S,15R,16S)-5-acetyloxy-6-hydroxy-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadecan-15-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0800	uM
Bortezomib	1762748: Inhibition of TNFalpha-induced NFkappaB activation in HEK293 cells assessed as luciferase expression by luciferase reporter activity assay	ic50	0.0850	uM
[(2R)-2-[(1S)-1-[(8S,9S,10R,13S,14S,17R)-10,13-dimethyl-1,4-dioxo-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-17-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0950	uM
(1S,2S,3’R,4S,4’R,8S,10S,13S,14R,18S,19R,21R)-8,18-dihydroxy-3’,4’,8,10,14-pentamethylspiro[5,20-dioxahexacyclo[11.9.0.02,10.04,9.014,19.019,21]docos-16-ene-6,5’-oxolane]-2’,15-dione	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.0950	uM
1-[[5-benzoyl-4-(trifluoromethyl)pyrimidin-2-yl]amino]-3-methylpyrrole-2,5-dione	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.0980	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-phenylpyrimidine-5-carboxylate	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.1000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-thiophen-3-ylpyrimidine-5-carboxylate	95093: Inhibition of NF-kB mediated transcriptional activation in Jurkat T-cells	ic50	0.1000	uM
[(2R)-2-[(1S)-1-[(1S,2R,7S,9R,11S,12S,15R,16S)-6-acetyloxy-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-15-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.1020	uM
(1S,2R,7R,9R,11S,12S,14S,15R,16S)-6-hydroxy-15-[(1S)-1-[(2R)-5-(hydroxymethyl)-4-methyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-2,14,16-trimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.1270	uM
(1S,2R,6S,7R,9R,11S,12S,15R,16S)-15-[(1S)-1-[(2R,4S,5R)-4,5-dimethyl-6-oxooxan-2-yl]-1-hydroxyethyl]-6,15-dihydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.1330	uM
(1S,2R,7S,9R,11S,12S,15S,16S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.1460	uM
2-chloro-8-(trifluoromethyl)-6H-pyrimido[4,5-b][1,5]benzothiazepin-5-one	1178334: Inhibition of NF-kappaB-mediated transcriptional activation in human Jurkat cells by luciferase reporter gene assay	ic50	0.2000	uM
N-(6-benzoyl-1H-benzimidazol-2-yl)-2-(1-thieno[3,2-d]pyrimidin-4-ylpiperidin-4-yl)-1,3-thiazole-4-carboxamide	1864336: Inhibition of NF kappa B activation (unknown origin)	ic50	0.2000	uM
3-(2-methoxyphenyl)-2-[2-(methylamino)-4-phenyl-1,3-thiazol-5-yl]quinazolin-4-one	1178339: Inhibition of NF-kappaB-mediated transcriptional activation in HEK293 cells by luciferase reporter gene assay	ic50	0.2000	uM
3-methyl-1-[[5-(4-methyl-1,3-oxazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione	95093: Inhibition of NF-kB mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
3-methyl-1-[[5-(2-methyltetrazol-5-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]pyrrole-2,5-dione	95093: Inhibition of NF-kB mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-(5-methylthiophen-2-yl)pyrimidine-5-carboxylate	95093: Inhibition of NF-kB mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
1-[[5-(4,5-dihydro-1,3-oxazol-2-yl)-2-thiophen-2-ylpyrimidin-4-yl]amino]-3-methylpyrrole-2,5-dione	95093: Inhibition of NF-kB mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
ethyl 4-[(3-methyl-2,5-dioxopyrrol-1-yl)amino]-2-methylsulfanylpyrimidine-5-carboxylate	95093: Inhibition of NF-kB mediated transcriptional activation in Jurkat T-cells	ic50	0.2000	uM
(1S,2R,5S,6S,7R,9R,11S,12S,15R,16S)-6-hydroxy-15-[(1S)-1-[(2R)-5-(hydroxymethyl)-4-methyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-2,16-dimethyl-5-piperidin-1-yl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadecan-3-one	1771376: Inhibition of TNF-alpha stimulated NF-KappaB in human HEK293 cells transfected with NF-kappaB-Luc incubated for 5 hrs by luciferase reporter gene assay	ic50	0.2090	uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects localization, affects binding, increases reaction, affects cotreatment, increases abundance (+2 more)	5
Arsenic Trioxide	decreases reaction, increases expression, decreases expression	4
Lipopolysaccharides	affects response to substance, affects cotreatment, increases expression, increases cleavage	4
Bortezomib	decreases cleavage, decreases expression	3
Air Pollutants	affects expression, increases abundance, increases expression	3
Methotrexate	affects cotreatment, increases expression, affects response to substance	3
Ozone	affects expression, increases abundance, increases expression, increases reaction, affects cotreatment (+1 more)	3
Silicon Dioxide	increases expression	3
Asbestos, Crocidolite	affects expression, decreases expression, increases expression	3
Particulate Matter	increases abundance, increases expression	3
deoxynivalenol	affects binding, decreases reaction, increases expression	2
zinc sulfide	affects cotreatment, decreases expression, increases expression	2
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cannabidiol	decreases expression, affects cotreatment	2
Cisplatin	decreases expression, increases expression, affects cotreatment	2
Ellagic Acid	decreases expression	2
Estradiol	increases expression	2
Nickel	increases expression	2
Plant Extracts	decreases expression, increases expression	2
Zinc	decreases expression, increases expression	2
Cyclosporine	increases expression	2
Gold Compounds	affects cotreatment, increases expression, decreases methylation	2
aristolochic acid I	increases expression	1
Glupearl 19S	increases expression	1
FR900359	increases phosphorylation	1
NMS-873	decreases metabolic processing	1
2-anisidine	affects expression	1
triphenyl phosphate	affects expression	1

ChEMBL screening assays

230 unique, capped per target: 226 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613870	Functional	PUBCHEM_BIOASSAY: Name: High Throughput Screen to Identify Compounds that increase expression of NF-kB in Human Neuronal Cells - Dose Response. (Class of assay: confirmatory) [Related pubchem assays: 1239 ]	PubChem BioAssay data set
CHEMBL3223786	Binding	Inhibition of NFkappaB in human FRT-Jurkat cells expressing GFP assessed as reduction of TNF expression at 10 uM after 24 hrs by flow cytometry relative to control	Novel thalidomide analogues with potent NFB and TNF expression inhibition — Medchemcomm

Cellosaurus cell lines

11 cell lines: 10 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0C41	JK-6L	Cancer cell line	Male
CVCL_A5DY	JK-6L.31H	Cancer cell line	Male
CVCL_A5DZ	JK-6L.39L	Cancer cell line	Male
CVCL_B0ZQ	Abcam Hep-G2 NFKB2 KO	Cancer cell line	Male
CVCL_B1DW	Abcam HCT 116 NFKB2 KO	Cancer cell line	Male
CVCL_D7VS	Ubigene A-549 NFKB2 KO	Cancer cell line	Male
CVCL_D8R9	Ubigene HCT 116 NFKB2 KO	Cancer cell line	Male
CVCL_D9L9	Ubigene HEK293 NFKB2 KO	Transformed cell line	Female
CVCL_E0J2	Ubigene HeLa NFKB2 KO	Cancer cell line	Female
CVCL_TA60	HAP1 NFKB2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

93 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT01946906	PHASE4	COMPLETED	The Rifaximin Study in CVID
NCT05193552	PHASE4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00168012	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	PHASE3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00542997	PHASE3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143	PHASE3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	PHASE3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT01489618	PHASE2	TERMINATED	Prime Boost Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02579967	PHASE2	RECRUITING	Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
NCT03663933	PHASE2	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation
NCT04339777	PHASE2	RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
NCT04925375	PHASE2	RECRUITING	Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease
NCT05593588	PHASE2	ENROLLING_BY_INVITATION	Senolytics Treatment of Interstitial Lung Disease in Common Variable Immunodeficiency
NCT06897358	PHASE2	ACTIVE_NOT_RECRUITING	Leniolisib for Immune Dysregulation in CVID
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00263237	PHASE1	COMPLETED	STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT00004695	Not specified	COMPLETED	Randomized Study of Polyethylene-Glycol-Conjugated Interleukin 2 in Patients With Common Variable Immunodeficiency
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00015431	Not specified	COMPLETED	Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms
NCT00661401	Not specified	COMPLETED	Specific IgG Antibody in Patients With Primary Antibody Deficiencies Treated With Subcutaneous Immunoglobulin
NCT00943514	Not specified	RECRUITING	Natural History of Bronchiectasis