NFKB1

Summary

NFKB1 (nuclear factor kappa B subunit 1, HGNC:7794) is a protein-coding gene on chromosome 4q24, encoding Nuclear factor NF-kappa-B p105 subunit (P19838). 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 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. NFKB is a critical regulator of the immediate-early response to viral infection. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed.

Source: NCBI Gene 4790 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency, common variable, 12 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 62
• Clinical variants (ClinVar): 947 total — 99 pathogenic, 49 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 152 molecules with ChEMBL bioactivity
• Transcription factor: yes — 457 downstream targets (CollecTRI)
• MANE Select transcript: NM_003998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7794
Approved symbol	NFKB1
Name	nuclear factor kappa B subunit 1
Location	4q24
Locus type	gene with protein product
Status	Approved
Aliases	KBF1, p105, NFKB-p50, p50, NF-kappaB, NFkappaB, NF-kB1
Ensembl gene	ENSG00000109320
Ensembl biotype	protein_coding
OMIM	164011
Entrez	4790

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 22 protein_coding, 10 retained_intron, 7 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000226574, ENST00000394820, ENST00000502367, ENST00000504044, ENST00000505458, ENST00000507079, ENST00000508584, ENST00000509165, ENST00000510638, ENST00000513803, ENST00000600343, ENST00000652569, ENST00000652619, ENST00000697793, ENST00000697794, ENST00000697795, ENST00000697796, ENST00000697797, ENST00000697798, ENST00000697799, ENST00000697800, ENST00000697801, ENST00000697802, ENST00000697803, ENST00000698233, ENST00000878339, ENST00000878340, ENST00000878341, ENST00000878342, ENST00000878343, ENST00000938143, ENST00000938144, ENST00000938145, ENST00000966659, ENST00000966660, ENST00000966661, ENST00000966662, ENST00000966663, ENST00000966664, ENST00000966665, ENST00000966666, ENST00000966667

RefSeq mRNA: 7 — MANE Select: NM_003998 NM_001165412, NM_001319226, NM_001382625, NM_001382626, NM_001382627, NM_001382628, NM_003998

CCDS: CCDS3657, CCDS54783

Canonical transcript exons

ENST00000226574 — 24 exons

Exon	Start	End
ENSE00000734504	102529836	102529914
ENSE00000734535	102533845	102533885
ENSE00001297248	102616434	102617302
ENSE00001361493	102501359	102501788
ENSE00003521949	102566987	102567135
ENSE00003529712	102537858	102537956
ENSE00003615915	102525512	102525557
ENSE00003784134	102576876	102577039
ENSE00003971018	102612434	102612606
ENSE00003971019	102584682	102584820
ENSE00003971020	102596138	102596332
ENSE00003971021	102600895	102601009
ENSE00003971022	102610575	102610699
ENSE00003971023	102607649	102607751
ENSE00003971024	102580535	102580639
ENSE00003971025	102612044	102612110
ENSE00003971026	102613425	102613581
ENSE00003971027	102607150	102607319
ENSE00003971028	102597520	102597661
ENSE00003971029	102606496	102606697
ENSE00003971030	102594892	102594981
ENSE00003971031	102593425	102593568
ENSE00003971032	102578881	102579039
ENSE00003971033	102582866	102582957

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 94.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.3564 / max 1781.6638, expressed in 1808 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49050	54.6828	1791
49049	2.6333	1277
49048	0.8268	505
49053	0.7089	256
49084	0.4500	168
49057	0.3106	84
49083	0.3087	119
49054	0.2985	118
49052	0.2485	77
49068	0.1770	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	94.60	gold quality
cartilage tissue	UBERON:0002418	94.50	gold quality
calcaneal tendon	UBERON:0003701	93.39	gold quality
monocyte	CL:0000576	92.60	gold quality
leukocyte	CL:0000738	92.52	gold quality
mononuclear cell	CL:0000842	92.51	gold quality
vermiform appendix	UBERON:0001154	91.91	gold quality
colonic epithelium	UBERON:0000397	91.50	gold quality
gall bladder	UBERON:0002110	91.42	gold quality
bone marrow cell	CL:0002092	90.51	gold quality
rectum	UBERON:0001052	90.31	gold quality
middle frontal gyrus	UBERON:0002702	90.17	gold quality
blood	UBERON:0000178	90.09	gold quality
granulocyte	CL:0000094	89.44	gold quality
mucosa of transverse colon	UBERON:0004991	89.35	gold quality
lymph node	UBERON:0000029	89.27	gold quality
upper lobe of left lung	UBERON:0008952	89.26	gold quality
omental fat pad	UBERON:0010414	89.23	gold quality
peritoneum	UBERON:0002358	89.19	gold quality
sural nerve	UBERON:0015488	89.19	gold quality
endocervix	UBERON:0000458	89.17	gold quality
islet of Langerhans	UBERON:0000006	89.15	gold quality
upper leg skin	UBERON:0004262	89.14	gold quality
ileal mucosa	UBERON:0000331	89.07	gold quality
ectocervix	UBERON:0012249	89.01	gold quality
left uterine tube	UBERON:0001303	88.99	gold quality
skin of leg	UBERON:0001511	88.72	gold quality
upper lobe of lung	UBERON:0008948	88.60	gold quality
right lung	UBERON:0002167	88.58	gold quality
skin of abdomen	UBERON:0001416	88.55	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	598.26
E-MTAB-8142	yes	85.19
E-CURD-46	yes	15.21
E-MTAB-8498	yes	10.00
E-GEOD-135922	yes	6.11
E-MTAB-6678	yes	6.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

457 targets.

Target	Regulation
A2M	Unknown
ABCA1	Repression
ABCB1	Activation
ABCG2	Activation
ACHE
ADGRG3
ADORA1	Activation
ADORA2A	Unknown
ADORA3	Unknown
AGER	Activation
AGR2
AGT	Unknown
AKR1B1	Activation
AKT1	Repression
AKT2	Repression
ALOX12	Repression
ALOX5	Repression
ALOX5AP	Unknown
AMH	Activation
APOC3	Activation
APOE
AQP2
AR	Repression
ATF3	Unknown
ATF6
ATP12A	Repression
AVP
B2M	Activation
BACE1	Repression
BAG1

JASPAR motifs

Motif	Name	Family
MA0105.1	NFKB1	NF-kappaB-related factors
MA0105.2	NFKB1	NF-kappaB-related factors
MA0105.3	NFKB1	NF-kappaB-related factors
MA0105.4	NFKB1	NF-kappaB-related factors

JASPAR matrix evidence (PMIDs): PMID:8449662, PMID:1406630, PMID:20066093

Upstream regulators (CollecTRI, top): AP1, APEX1, AR, BCL3, BCL6, BTF3, CEBPA, CEBPG, EGR1, ELF1, ELF4, EP300, ESR1, ETS1, ETV3, FHL2, FOS, FOXO3, FOXP3, GATA3, HDAC1, HDAC9, HOXA9, HSF1, IRF6, LYL1, MAP3K7, NFKB1, NFKB, NFKBIA, NFX1, NOTCH1, NR1H4, NR1I2, NR3C1, PARP1, PAX1, PIR, PPARGC1A, RBPJ

miRNA regulators (miRDB)

70 targeting NFKB1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• This lithium-induced up-regulation of NF-kappa B and MAP kinase activation was associated with an enhancement of interleukin-8 mRNA accumulation as well as an increase in interleukin-8 protein release. (PMID:11756416)
• CD14-dependent activation of NF-kappaB by filarial parasitic sheath proteins (PMID:11779220)
• The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex. (PMID:11830587)
• Critical role of tumor necrosis factor-alpha and NF-kappa B in interferon-gamma -induced CD40 expression in microglia/macrophages. (PMID:11830590)
• Incontinentia pigmenti: the first single gene disorder due to disrupted NF-kappa B function (PMID:11859566)
• NFKB-p50 is a binding protein in the negative regulatory element of the epsilon-globin gene. (PMID:11942414)
• NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105 (PMID:11953428)
• IRF-3-dependent, NFkappa B- and JNK-independent activation of the 561 and IFN-beta genes in response to double-stranded RNA (PMID:11972054)
• NF-KB could be considered as a coordinating element in the body’s response to stress, infection, or inflammation, and it may be a good therapeutic target. (PMID:11980335)
• Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF(-kappa)B transcription factors (PMID:12019209)
• results suggest that NFkappaB is involved in the IL-1beta-induced COX-2 expression in the mesenchymal cells of human amnion (PMID:12021045)
• NF-kappaB activates Bcl-2 expression in t(14;18) lymphoma cells. (PMID:12032828)
• NF-kappaB-dependent MnSOD expression protects adenocarcinoma cells from TNF-alpha-induced apoptosis. (PMID:12032830)
• Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to multiple sclerosis (PMID:12058256)
• Differential activation of nuclear factor-kappa B by monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in smooth muscle cells. (PMID:12067898)
• MUC2 upregulated by PMA Phorbol 12-myristate 13-acetate includes a role for NF-kB (PMID:12077118)
• Low intracellular zinc impairs the translocation of activated NF-kappa B to the nuclei in human neuroblastoma IMR-32 cells. (PMID:12089148)
• NO can influence cell death by modulating NF-kappaB activity with the sites of inhibition being cell type-specific. (PMID:12091382)
• mechanisms that underlie CD40-mediated activation of NF-kappaB in airway epithelial cells (PMID:12122011)
• NF-kappaB is a major and essential factor in regulating the expression of cytokine and plays a fundamental role in the pathogenesis of ulcerative colitis UC. (PMID:12133438)
• Induction of IkappaB: atrial natriuretic peptide as a regulator of the NF-kappaB pathway (PMID:12135603)
• Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. (PMID:12145210)
• Mitogen-activated protein kinases and nuclear factor-kappaB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages. (PMID:12150710)
• Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein. (PMID:12150997)
• NF-kappaB seems important in modulating of immunoregulatory genes relevant in critical illnesses. (PMID:12166787)
• Depletion of intracellular GTP results in nuclear factor-kappaB activation and intercellular adhesion molecule-1 expression in human endothelial cells. (PMID:12181421)
• APC inhibited both the binding of NF-kB to target sites and the degradation of I kappa B alpha, and inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways. (PMID:12195699)
• characterized activity in S-type neuroblastoma cells and determined its role in their survival (PMID:12198114)
• inhibition of its transcriptional activity by protein kinase A (PMID:12230568)
• These results point to the negative regulation of osteoblast differentiation by NFkappaB, with implications in the pathogenesis and progression of osteosarcomas. (PMID:12237108)
• Mutation of this protein’s promoter binding site (-45 bp) impaired the ability of ITGB3BP to downregulate the urokinase-type plasminogen activator receptor promoter activity. (PMID:12244126)
• NF-kappaB can be a central regulator of chemokine gene expression in BFT-stimulated intestinal epithelial cells and may be an important regulator of neutrophil migration. (PMID:12296854)
• NFkB, I-kBalpha and I-kB kinase are present in platelets; upon platelet activation, the NF-kappaB/I-kappaBalpha complex is dissociated by phosphorylation of I-kB and proteolysis. (PMID:12297126)
• Bovine serum albumin induced an increase in the expression of this protein in human kidney proximal tubule cells in culture. (PMID:12297724)
• Cytokines trigger this transcriptional factor to be expressed in human stomach neoplasm cells cultivated in vitro. (PMID:12297725)
• nf-kappa B activity plays role in apoptosis of hepatocellular carcinoma (PMID:12365017)
• These data suggest that the subcellular location of I(kappa)B(alpha) is a critical determinant in ionizing radiation-induced nuclear factor-kappaB activation. (PMID:12388747)
• NFkappaB response to anti-beta(2)GP1 antibodies is indirect, and is an essential intermediate in the activation of endothelial cells by anti-beta(2)GP1 antibodies (PMID:12428105)
• NF-kappaB may play a key regulatory role in skeletal muscle wasting associated with cachexia (PMID:12431991)
• found in mitochondria; regulates mitochondrial gene expression (PMID:12433922)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nfkb1	ENSDARG00000105261
mus_musculus	Nfkb1	ENSMUSG00000028163
rattus_norvegicus	Nfkb1	ENSRNOG00000023258
drosophila_melanogaster	Dif	FBGN0011274
drosophila_melanogaster	dl	FBGN0260632

Paralogs (4): NFKB2 (ENSG00000077150), RELB (ENSG00000104856), REL (ENSG00000162924), RELA (ENSG00000173039)

Protein

Protein identifiers

Nuclear factor NF-kappa-B p105 subunit — P19838 (reviewed: P19838)

Alternative names: DNA-binding factor KBF1, EBP-1, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

All UniProt accessions (6): P19838, A0A494C157, A0A494C1E9, A0A8V8TLB2, D6RC45, D6RH30

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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B. Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105. Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65-p50 complex to form a transcription factor. Together with RELA/p65, 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.

Subunit / interactions. Component of the NF-kappa-B p65-p50 complex. Homodimer; component of the NF-kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 complex. Component of the NF-kappa-B p50-c-Rel complex. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Also interacts with MAP3K8. NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its histone acetyltransferase activity. Interacts with TSC22D3; this interaction prevents nuclear translocation and DNA-binding. Interacts with SPAG9 and UNC5CL. NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50. NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2. Interacts with GSK3B; the interaction prevents processing of p105 to p50. NFKB1/p50 interacts with NFKBIE. NFKB1/p50 interacts with NFKBIZ. Nuclear factor NF-kappa-B p50 subunit interacts with NFKBID. Directly interacts with MEN1. Interacts with HIF1AN. Interacts with FEM1A; interaction is direct.

Subcellular location. Cytoplasm Nucleus. Cytoplasm.

Post-translational modifications. Generation of the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) transcription factor takes place both cotranslationally and post-translationally via non-mutually exclusive mechanisms. A cotranslational processing allows the production of both p50 and p105 (Nuclear factor NF-kappa-B p105 subunit) from a single NFKB1 mRNA. While translation occurs, the particular unfolded structure after the GRR repeat region acts as a substrate for the proteasome, promoting degradation of the C-terminus. The GRR acts as a proteasomal ‘stop signal’, protecting the region upstream of the GRR from degradation and promoting generation of p50. It is unclear if limited proteasome degradation during cotranslational processing depends on ubiquitination. NF-kappa-B p50 is also generated post-translationally following ubiquitination by the KPC complex, leading to limited processing by the proteasome downstream of the GRR region, thereby generating p50. Phosphorylation at the C-terminus by IKBKB/IKKB acts as a signal for ubiquitination and promotes either complete degradation or processing to generate the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit). Phosphorylation at Ser-903 and Ser-907 primes p105 for proteolytic processing in response to TNF stimulation. Phosphorylation at Ser-923, Ser-927 and Ser-932 are required for BTRC/BTRCP-mediated ubiquitination and proteolysis. Phosphorylation at Ser-927 is also required for ubiquitination by the KPC complex and limited processing to generate NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit). Polyubiquitinated at multiple Lys residues in the C-terminus. Polyubiquitinated by the SCF(FBXW11) and SCF(BTRC) complexes following phosphorylation at Ser-923, Ser-927 and Ser-932, leading to its complete degradation. In contrast, polyubiquitination by the KPC complex following phosphorylation at Ser-927 leads to limited proteosomal processing and generation of the active NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit). S-nitrosylation of Cys-61 affects DNA binding. The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.

Disease relevance. Immunodeficiency, common variable, 12, with autoimmunity (CVID12) [MIM:616576] A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, and transcription activation. Glycine-rich region (GRR) is a critical element in the generation of p50 (Nuclear factor NF-kappa-B p50 subunit) by acting as a proteasomal ‘stop signal’, which leads to limited proteasomal degradation of the C-terminus, while generating p50.

Induction. By phorbol ester and TNF.

Isoforms (3)

UniProt ID	Names	Canonical?
P19838-1	1	yes
P19838-2	2
P19838-3	3

RefSeq proteins (7): NP_001158884, NP_001306155, NP_001369554, NP_001369555, NP_001369556, NP_001369557, NP_003989* (*=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
IPR030503	NF-kB_p105_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
IPR047096	NF-kB_p105_DD	Domain

Pfam: PF00531, PF00554, PF12796, PF16179

UniProt features (105 total): strand 24, helix 16, modified residue 16, mutagenesis site 8, sequence conflict 8, repeat 7, sequence variant 6, region of interest 4, turn 4, splice variant 3, chain 2, domain 2, short sequence motif 1, compositionally biased region 1, site 1, lipid moiety-binding region 1, cross-link 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8TQD	X-RAY DIFFRACTION	2.02
7LFC	X-RAY DIFFRACTION	2.1
7RG5	X-RAY DIFFRACTION	2.15
7LEQ	X-RAY DIFFRACTION	2.24
7LET	X-RAY DIFFRACTION	2.4
1SVC	X-RAY DIFFRACTION	2.6
7RG4	X-RAY DIFFRACTION	2.6
1NFI	X-RAY DIFFRACTION	2.7
2O61	X-RAY DIFFRACTION	2.8
7LF4	X-RAY DIFFRACTION	2.85
3GUT	X-RAY DIFFRACTION	3.59
1MDI	SOLUTION NMR
1MDJ	SOLUTION NMR
1MDK	SOLUTION NMR
2DBF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19838-F1	73.84	0.45

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 (1): 433–434 (cleavage (when cotranslationally processed))

Post-translational modifications (18): 61, 337, 431, 440, 441, 449, 678, 759, 892, 903, 907, 923, 927, 932, 937, 943, 61, 325

Mutagenesis-validated functional residues (8):

Position	Phenotype
61	suppresses s-nitrosylation-induced inhibition of dna-binding activity. loss of s-(15-deoxy-delta12,14-prostaglandin j2-9
678	fails to promote hif1an-dependent 2-oxoglutarate decarboxylation.
903	prevents p105 proteolysis in response to tnf.
907	prevents p105 proteolysis in response to tnf.
921	decrease in stimuli-induced phosphorylation. loss of phosphorylation; when associated with a-923 and a-932.
923	decrease in stimuli-induced phosphorylation. loss of phosphorylation; when associated with a-921 and a-932.
927	decreased phosphorylation by ikbkb/ikkb and decreased generation of the nf-kappa-b p50 subunit from p105.
932	decrease in stimuli-induced phosphorylation. loss of phosphorylation; when associated with a-921 and a-923.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1810476	RIP-mediated NFkB activation via ZBP1
R-HSA-193692	Regulated proteolysis of p75NTR
R-HSA-202424	Downstream TCR signaling
R-HSA-209560	NF-kB is activated and signals survival
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-3134963	DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-448706	Interleukin-1 processing
R-HSA-5603029	IkBA variant leads to EDA-ID
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-5660668	CLEC7A/inflammasome pathway
R-HSA-5684264	MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-6798695	Neutrophil degranulation
R-HSA-844456	The NLRP3 inflammasome
R-HSA-8853884	Transcriptional Regulation by VENTX
R-HSA-9020702	Interleukin-1 signaling
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-9609690	HCMV Early Events
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses
R-HSA-9818749	Regulation of NFE2L2 gene expression
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-9958825	Activation of STAT3 by cadherin engagement

MSigDB gene sets: 891 (showing top): PID_BCR_5PATHWAY, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, BIOCARTA_GCR_PATHWAY, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, BIOCARTA_TNFR2_PATHWAY, PID_HDAC_CLASSI_PATHWAY, BIOCARTA_RELA_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LIPID_STORAGE, BIOCARTA_FMLP_PATHWAY, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_CELLULAR_RESPONSE_TO_VIRUS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_GLAND_MORPHOGENESIS

GO Biological Process (49): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), apoptotic process (GO:0006915), inflammatory response (GO:0006954), canonical NF-kappaB signal transduction (GO:0007249), JNK cascade (GO:0007254), negative regulation of gene expression (GO:0010629), positive regulation of macrophage derived foam cell differentiation (GO:0010744), positive regulation of cholesterol efflux (GO:0010875), positive regulation of lipid storage (GO:0010884), negative regulation of vitamin D biosynthetic process (GO:0010957), negative regulation of interleukin-12 production (GO:0032695), tumor necrosis factor-mediated signaling pathway (GO:0033209), response to muscle stretch (GO:0035994), non-canonical NF-kappaB signal transduction (GO:0038061), negative regulation of apoptotic process (GO:0043066), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of inflammatory response (GO:0050728), B cell receptor signaling pathway (GO:0050853), mammary gland involution (GO:0060056), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), cellular response to lipopolysaccharide (GO:0071222), cellular response to mechanical stimulus (GO:0071260), cellular response to nicotine (GO:0071316), cellular response to interleukin-6 (GO:0071354), cellular response to dsRNA (GO:0071359), positive regulation of canonical Wnt signaling pathway (GO:0090263), cellular response to interleukin-17 (GO:0097398), cellular response to virus (GO:0098586), antibacterial innate immune response (GO:0140367), negative regulation of cytokine production involved in inflammatory response (GO:1900016), positive regulation of hyaluronan biosynthetic process (GO:1900127), cellular response to angiotensin (GO:1904385), positive regulation of miRNA metabolic process (GO:2000630), MAPK cascade (GO:0000165), negative regulation of cytokine production (GO:0001818), immune system process (GO:0002376), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (15): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), transcription coregulator activity (GO:0003712), identical protein binding (GO:0042802), actinin binding (GO:0042805), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), protein sequestering activity (GO:0140311)

GO Cellular Component (12): chromatin (GO:0000785), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), I-kappaB/NF-kappaB complex (GO:0033256), secretory granule lumen (GO:0034774), NF-kappaB p50/p65 complex (GO:0035525), specific granule lumen (GO:0035580)

Reactome top-level categories

Rollup of top-24 pathways:

Category	Pathways
Interleukin-1 signaling	2
C-type lectin receptors (CLRs)	2
Downstream signaling events of B Cell Receptor (BCR)	1
ZBP1(DAI) mediated induction of type I IFNs	1
p75 NTR receptor-mediated signalling	1
TCR signaling	1
p75NTR signals via NF-kB	1
Cellular Senescence	1
Fc epsilon receptor (FCERI) signaling	1
Cytosolic sensors of pathogen-associated DNA	1
Chromatin modifying enzymes	1
Adipogenesis	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
Toll Like Receptor 3 (TLR3) Cascade	1
TRIF (TICAM1)-mediated TLR4 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
DNA-templated transcription	2
intracellular signaling cassette	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
binding	2
transcription regulator activity	2
protein binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
MAPK cascade	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
regulation of lipid storage	1
lipid storage	1
positive regulation of cellular process	1
positive regulation of lipid localization	1
negative regulation of steroid biosynthetic process	1
vitamin D biosynthetic process	1
negative regulation of vitamin metabolic process	1
regulation of vitamin D biosynthetic process	1
negative regulation of cytokine production	1
interleukin-12 production	1
regulation of interleukin-12 production	1

Protein interactions and networks

STRING

9484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NFKB1	TNF	P01375	995
NFKB1	JUN	P05412	992
NFKB1	TP53	P04637	989
NFKB1	RELB	Q01201	987
NFKB1	RELA	Q04206	987
NFKB1	REL	Q04864	987
NFKB1	NFKBIA	P25963	986
NFKB1	BCL3	P20749	984
NFKB1	NFKB2	Q00653	984
NFKB1	EP300	Q09472	981
NFKB1	HDAC1	Q13547	981
NFKB1	IKBKB	O14920	979
NFKB1	CHUK	O15111	966
NFKB1	IL1B	P01584	960
NFKB1	IKBKG	Q9Y6K9	953

IntAct

382 interactions, top by confidence:

A	B	Type	Score
MAP3K8	NFKB1	psi-mi:“MI:0914”(association)	0.930
NFKBIA	NFKB1	psi-mi:“MI:0915”(physical association)	0.930
NFKBIA	NFKB1	psi-mi:“MI:0914”(association)	0.930
RELA	NFKB1	psi-mi:“MI:0914”(association)	0.920
RELA	NFKB1	psi-mi:“MI:0915”(physical association)	0.920
NFKB1	RELA	psi-mi:“MI:0915”(physical association)	0.920
NFKB1	NFKB1	psi-mi:“MI:0407”(direct interaction)	0.760
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.760
SMAD4	SMAD9	psi-mi:“MI:0914”(association)	0.750
HIF1AN	NFKB1	psi-mi:“MI:0915”(physical association)	0.740
HIF1AN	NFKB1	psi-mi:“MI:0407”(direct interaction)	0.740
NFKB1	HIF1AN	psi-mi:“MI:0915”(physical association)	0.740
HIF1AN	NFKB1	psi-mi:“MI:0210”(hydroxylation reaction)	0.740
MTMR2	CCDC22	psi-mi:“MI:0914”(association)	0.730
NFKB1	FBXW11	psi-mi:“MI:0914”(association)	0.690
RPS3	NFKB1	psi-mi:“MI:0915”(physical association)	0.620
RPS3	NFKB1	psi-mi:“MI:0914”(association)	0.620
NFKB1	RPS3	psi-mi:“MI:0915”(physical association)	0.620
NFKB1	PELP1	psi-mi:“MI:0915”(physical association)	0.520
NFKB1	PLD3	psi-mi:“MI:0915”(physical association)	0.520
	NFKB1	psi-mi:“MI:0915”(physical association)	0.460
NFKB1		psi-mi:“MI:0403”(colocalization)	0.460
NFKB1	E3	psi-mi:“MI:0915”(physical association)	0.400
TWIST1	NFKB1	psi-mi:“MI:0915”(physical association)	0.400
NFKB1	NFKBIA	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (618): NFKB1 (Reconstituted Complex), RELA (Reconstituted Complex), NFKB1 (Affinity Capture-MS), RELA (Reconstituted Complex), RELA (Reconstituted Complex), NFKB1 (Affinity Capture-Western), NFKB1 (Reconstituted Complex), NFKB1 (Affinity Capture-Western), NFKB1 (Affinity Capture-Western), ECSIT (Affinity Capture-Western), RELA (Affinity Capture-Western), NFKB1 (Reconstituted Complex), NFKB1 (Two-hybrid), PPARG (Affinity Capture-Western), PPARG (Reconstituted Complex)

ESM2 similar proteins: A0A8M9QN10, A1L1G9, A2BGA0, A3KN19, A4QP72, A6H8H2, B0BF33, B0JZV4, E7FDW2, F1QJF4, F7BJB9, O15013, O73630, P19838, P25799, P51448, P59997, P68907, P98150, Q04861, Q08AE8, Q12923, Q1LYM3, Q3U1T9, Q5SWY7, Q5VZ89, Q5XGY0, Q5XK72, Q63369, Q64512, Q66JF7, Q69ZS0, Q6F3J0, Q6PF42, Q6ZUJ8, Q7SYN5, Q7Z3E5, Q7Z401, Q803Q4, Q8C033

Diamond homologs: A2ARS0, B2RXR6, C7B178, C9JTQ0, P0C927, P19838, Q00PJ3, Q07E43, Q08353, Q21920, Q29RM5, Q2QL84, Q337A0, Q3KP44, Q3SX00, Q3UES3, Q3UUF8, Q4FE45, Q4JHE0, Q4V890, Q502K3, Q5R8C8, Q5ZLC8, Q60J38, Q6KAE5, Q6TNT2, Q76K24, Q7EZ44, Q86W74, Q86WC6, Q8BTI7, Q8BTZ5, Q8C0T1, Q8NB46, Q8VHS5, Q9BSK4, Q9D119, Q9H2K2, Q9N3Q8, Q9Z2G1

SIGNOR signaling

51 interactions.

A	Effect	B	Mechanism
NFKBIE	down-regulates	NFKB1	binding
IKBKB	“down-regulates activity”	NFKB1	phosphorylation
RBX1	up-regulates	NFKB1	ubiquitination
NOTCH1	“up-regulates quantity by expression”	NFKB1	“transcriptional regulation”
AKT2	up-regulates	NFKB1
PRKACA	up-regulates	NFKB1	phosphorylation
NFKBIA	“down-regulates activity”	NFKB1	binding
CASP8AP2	up-regulates	NFKB1	binding
CHEK1	down-regulates	NFKB1	phosphorylation
NFKB1	down-regulates	MAP3K8	binding
NR3C1	“down-regulates quantity by repression”	NFKB1	“transcriptional regulation”
POMC	“down-regulates activity”	NFKB1
NFKB1	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”
BTF3	“down-regulates quantity by repression”	NFKB1	“transcriptional regulation”
NFKB1	“down-regulates quantity by repression”	CTCF	“transcriptional regulation”
BCL3	“up-regulates activity”	NFKB1	binding
NFKB1	“down-regulates quantity by repression”	THBD	“transcriptional regulation”
PERP	“down-regulates quantity”	NFKB1	ubiquitination
NFKB1	“down-regulates quantity by repression”	BMP4	“transcriptional regulation”
RNF123	“down-regulates quantity by destabilization”	NFKB1	polyubiquitination
BCL10	“up-regulates quantity by expression”	NFKB1	“transcriptional regulation”
TNFSF10	“up-regulates quantity by expression”	NFKB1	“post transcriptional regulation”
NFKB1	“up-regulates quantity by expression”	hsa-miR-146a	“post transcriptional regulation”
2,5-dimethylcelecoxib	“down-regulates activity”	NFKB1	“chemical inhibition”
NFKB1	“form complex”	NfKb-p65/p50	binding
NFKB1	“up-regulates activity”	RELA	binding
MAP3K7	“up-regulates quantity by expression”	NFKB1	“transcriptional regulation”
NFKB1	“up-regulates quantity by expression”	IEX-1L	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	5	45.5×	1e-05
Deadenylation of mRNA	5	38.5×	2e-05
M-decay: degradation of maternal mRNAs by maternally stored factors	5	28.6×	6e-05
Formation of TC-NER Pre-Incision Complex	5	18.6×	4e-04
Neddylation	19	15.8×	7e-16

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	5	64.7×	7e-06
regulatory ncRNA-mediated gene silencing	5	54.4×	9e-06
obsolete negative regulation of NF-kappaB transcription factor activity	5	28.9×	2e-04
regulation of translation	5	17.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	99
Likely pathogenic	49
Uncertain significance	399
Likely benign	299
Benign	60

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027409	NM_003998.4(NFKB1):c.418_427del (p.Leu140fs)	Pathogenic
1064676	NM_003998.4(NFKB1):c.139del (p.Ile47fs)	Pathogenic
1064678	NM_003998.4(NFKB1):c.469C>T (p.Arg157Ter)	Pathogenic
1064682	NM_003998.4(NFKB1):c.1012del (p.Ser338fs)	Pathogenic
1069169	NC_000004.11:g.(?103488144)(103505977_?)del	Pathogenic
1070135	NM_003998.4(NFKB1):c.2382T>G (p.Tyr794Ter)	Pathogenic
1070835	NM_003998.4(NFKB1):c.2265T>A (p.Tyr755Ter)	Pathogenic
1073467	NM_003998.4(NFKB1):c.208_209insA (p.Leu70fs)	Pathogenic
1352196	NM_003998.4(NFKB1):c.1190del (p.Gly397fs)	Pathogenic
1355449	NM_003998.4(NFKB1):c.357_358del (p.Cys119_Glu120delinsTer)	Pathogenic
1373688	NM_003998.4(NFKB1):c.2603dup (p.Thr869fs)	Pathogenic
1419528	NM_003998.4(NFKB1):c.1616del (p.Val539fs)	Pathogenic
1434457	NM_003998.4(NFKB1):c.896del (p.Gly299fs)	Pathogenic
1437606	NM_003998.4(NFKB1):c.1853_1854del (p.Ser618fs)	Pathogenic
1442609	NM_003998.4(NFKB1):c.498_499dup (p.Asn167fs)	Pathogenic
1450830	NM_003998.4(NFKB1):c.556dup (p.Asp186fs)	Pathogenic
1452916	NM_003998.4(NFKB1):c.1040dup (p.Leu349fs)	Pathogenic
1455978	NM_003998.4(NFKB1):c.1114del (p.Ser372fs)	Pathogenic
1456064	NM_003998.4(NFKB1):c.1356del (p.Asp452fs)	Pathogenic
1460013	NC_000004.11:g.(?103446676)(103488312_?)del	Pathogenic
1460014	NC_000004.11:g.(?103446676)(103446734_?)del	Pathogenic
2008911	NM_003998.4(NFKB1):c.2438del (p.Ala813fs)	Pathogenic
2013795	NM_003998.4(NFKB1):c.538C>T (p.Gln180Ter)	Pathogenic
2017111	NM_003998.4(NFKB1):c.1125del (p.Phe375fs)	Pathogenic
2025699	NM_003998.4(NFKB1):c.2122del (p.Glu708fs)	Pathogenic
2028263	NM_003998.4(NFKB1):c.2279_2280del (p.Ser760fs)	Pathogenic
2028540	NM_003998.4(NFKB1):c.317del (p.Asn106fs)	Pathogenic
2028923	NM_003998.4(NFKB1):c.376_377del (p.Val126fs)	Pathogenic
2032294	NM_003998.4(NFKB1):c.1781dup (p.Gln595fs)	Pathogenic
2034265	NM_003998.4(NFKB1):c.884G>A (p.Trp295Ter)	Pathogenic

SpliceAI

3883 predictions. Top by Δscore:

Variant	Effect	Δscore
4:102525558:G:GG	donor_gain	1.0000
4:102529911:ACAGG:A	donor_loss	1.0000
4:102529912:CAGG:C	donor_loss	1.0000
4:102529914:GGT:G	donor_loss	1.0000
4:102529915:G:C	donor_loss	1.0000
4:102529916:T:A	donor_loss	1.0000
4:102537957:G:GG	donor_gain	1.0000
4:102576874:A:AG	acceptor_gain	1.0000
4:102576875:G:GG	acceptor_gain	1.0000
4:102578841:A:AG	acceptor_gain	1.0000
4:102578848:T:TA	acceptor_gain	1.0000
4:102578849:G:A	acceptor_gain	1.0000
4:102578853:AT:A	acceptor_gain	1.0000
4:102578854:T:G	acceptor_gain	1.0000
4:102579035:CAGTA:C	donor_gain	1.0000
4:102579037:GTA:G	donor_gain	1.0000
4:102579038:TA:T	donor_gain	1.0000
4:102579040:G:GG	donor_gain	1.0000
4:102580526:T:A	acceptor_gain	1.0000
4:102580528:T:TA	acceptor_gain	1.0000
4:102580529:GAACA:G	acceptor_loss	1.0000
4:102580532:CA:C	acceptor_loss	1.0000
4:102580533:A:AC	acceptor_loss	1.0000
4:102580533:A:AG	acceptor_gain	1.0000
4:102580534:G:GG	acceptor_gain	1.0000
4:102580534:G:GT	acceptor_loss	1.0000
4:102580534:GA:G	acceptor_gain	1.0000
4:102580534:GAA:G	acceptor_gain	1.0000
4:102580534:GAAGC:G	acceptor_gain	1.0000
4:102582857:T:TA	acceptor_gain	1.0000

AlphaMissense

6372 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:102533878:C:A	P50H	1.000
4:102537859:G:T	R53I	1.000
4:102537860:A:C	R53S	1.000
4:102537860:A:T	R53S	1.000
4:102537861:G:A	G54R	1.000
4:102537861:G:C	G54R	1.000
4:102537862:G:A	G54E	1.000
4:102537864:T:C	F55L	1.000
4:102537865:T:C	F55S	1.000
4:102537865:T:G	F55C	1.000
4:102537866:T:A	F55L	1.000
4:102537866:T:G	F55L	1.000
4:102537867:C:A	R56S	1.000
4:102537867:C:G	R56G	1.000
4:102537870:T:A	F57I	1.000
4:102537870:T:C	F57L	1.000
4:102537870:T:G	F57V	1.000
4:102537871:T:C	F57S	1.000
4:102537871:T:G	F57C	1.000
4:102537872:C:A	F57L	1.000
4:102537872:C:G	F57L	1.000
4:102537873:C:A	R58S	1.000
4:102537876:T:C	Y59H	1.000
4:102537876:T:G	Y59D	1.000
4:102537877:A:G	Y59C	1.000
4:102537882:T:C	C61R	1.000
4:102537883:G:A	C61Y	1.000
4:102537886:A:T	E62V	1.000
4:102537888:G:C	G63R	1.000
4:102537888:G:T	G63C	1.000

dbSNP variants (sampled 300 via entrez): RS1000018326 (4:102547531 A>T), RS1000133096 (4:102502091 CTT>C), RS1000158424 (4:102513939 C>T), RS1000200439 (4:102510567 A>G), RS1000247392 (4:102540207 A>G), RS1000248329 (4:102541103 C>T), RS1000308135 (4:102516062 A>C,G), RS1000325976 (4:102526023 T>C,G), RS1000416244 (4:102578353 C>T), RS1000426500 (4:102562946 A>C), RS1000432686 (4:102533281 C>T), RS1000446958 (4:102565023 A>G), RS1000528145 (4:102588020 T>C), RS1000531782 (4:102519530 C>T), RS1000584010 (4:102590931 A>C,T)

Disease associations

OMIM: gene MIM:164011 | disease phenotypes: MIM:616576, MIM:608644, MIM:607594

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency, common variable, 12	Strong	Autosomal dominant
common variable immunodeficiency	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
immunodeficiency, common variable, 12	Moderate	AD

Mondo (3): immunodeficiency, common variable, 12 (MONDO:0014697), primary ciliary dyskinesia 3 (MONDO:0012085), common variable immunodeficiency (MONDO:0015517)

Orphanet (3): OBSOLETE: Common variable immunodeficiency (Orphanet:1572), NFKB1-related immune dysregulation (Orphanet:696874), Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001581	Recurrent skin infections
HP:0001596	Alopecia
HP:0001873	Thrombocytopenia
HP:0001890	Autoimmune hemolytic anemia
HP:0002110	Bronchiectasis
HP:0002582	Atrophic gastritis
HP:0002719	Recurrent infections
HP:0003581	Adult onset
HP:0003621	Juvenile onset
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0005387	Combined immunodeficiency
HP:0005425	Recurrent sinopulmonary infections
HP:0006510	Chronic pulmonary obstruction
HP:0006532	Recurrent pneumonia
HP:0011108	Recurrent sinusitis
HP:0011463	Childhood onset
HP:0025452	Pyoderma gangrenosum

GWAS associations

62 associations (top):

Study	Trait	p-value
GCST001010_13	Primary biliary cholangitis	4.000000e-12
GCST001198_30	Multiple sclerosis	1.000000e-07
GCST001458_2	Schizophrenia (treatment resistant)	2.000000e-07
GCST001685_5	Primary biliary cholangitis	1.000000e-07
GCST001728_8	Ulcerative colitis	4.000000e-12
GCST002251_9	Homeostasis model assessment of beta-cell function (dietary factor interaction)	7.000000e-06
GCST002938_19	Copper levels	2.000000e-06
GCST003129_19	Primary biliary cholangitis	8.000000e-10
GCST003372_30	Glomerular filtration rate (creatinine)	4.000000e-12
GCST003995_7	Tonsillectomy	5.000000e-14
GCST004030_20	Primary sclerosing cholangitis	1.000000e-07
GCST004131_126	Inflammatory bowel disease	4.000000e-06
GCST004132_34	Crohn’s disease	4.000000e-08
GCST004145_3	Primary biliary cholangitis	1.000000e-07
GCST004302_9	Primary biliary cholangitis	2.000000e-10
GCST004600_151	Eosinophil percentage of white cells	6.000000e-09
GCST004606_132	Eosinophil count	9.000000e-12
GCST004609_52	Monocyte percentage of white cells	1.000000e-09
GCST004617_97	Eosinophil percentage of granulocytes	1.000000e-10
GCST004623_3	Neutrophil percentage of granulocytes	5.000000e-09
GCST004624_78	Sum eosinophil basophil counts	9.000000e-11
GCST004632_108	Lymphocyte percentage of white cells	2.000000e-21
GCST004633_50	Neutrophil percentage of white cells	1.000000e-14
GCST005014_130	Tonsillectomy	5.000000e-14
GCST005537_19	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-18
GCST005581_2	Primary biliary cirrhosis	8.000000e-14
GCST005987_33	Albumin-globulin ratio	1.000000e-12
GCST005989_10	Serum total protein levels	1.000000e-08
GCST005990_46	Non-albumin protein levels	1.000000e-15
GCST006408_10	Allergic sensitization	2.000000e-08

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0004469	HOMA-B
EFO:0008111	diet measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0005128	albumin:globulin ratio measurement
EFO:0005298	allergic sensitization measurement
EFO:0004761	uric acid measurement
EFO:0009933	Thyroid preparation use measurement
EFO:0004847	age at onset
EFO:0007992	basophil percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D017074	Common Variable Immunodeficiency	C20.673.330
C535278	Primary ciliary dyskinesia, 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094258 (PROTEIN COMPLEX GROUP), CHEMBL3251 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

152 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 816,511 (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
CHEMBL1002	LEVOSALBUTAMOL	4	27,028
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1109	SULFAPHENAZOLE	4	4,065
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1180725	PROPANTHELINE	4	5,428
CHEMBL1190	DECAMETHONIUM	4	1,139
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4	3,903
CHEMBL1200873	PHENTOLAMINE MESYLATE	4	3,508
CHEMBL1215	PHENYLEPHRINE	4	37,782
CHEMBL1233	CARISOPRODOL	4	37,387
CHEMBL1238	AZELAIC ACID	4	152,287
CHEMBL1256696	CARBETAPENTANE CITRATE	4	2,413
CHEMBL1256841	NIALAMIDE	4
CHEMBL1256958	EPINEPHRINE BITARTRATE	4
CHEMBL1274	NILUTAMIDE	4
CHEMBL1370	BUDESONIDE	4
CHEMBL1405	ESTRONE	4
CHEMBL1411979	METHAPYRILENE	4
CHEMBL1423	PIMOZIDE	4
CHEMBL1451	TRIAMCINOLONE	4
CHEMBL1472989	BISOPROLOL FUMARATE	4
CHEMBL1489	AZACITIDINE	4

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

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs28362491	NFKB1		0.00	0
rs230504	NFKB1		0.00	0
rs230493	NFKB1		0.00	0
rs3774959	NFKB1		0.00	0
rs230539	NFKB1		0.00	0
rs4699030	NFKB1		0.00	0
rs3774932	NFKB1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

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

Binding affinities (BindingDB)

17 measured of 86 human assays (86 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(1E,4E)-1,5-dipyridin-3-ylpenta-1,4-dien-3-one	IC50	3400 nM	US-9187397: Therapeutic curcumin derivatives
(1E,4E)-1,5-dipyridin-4-ylpenta-1,4-dien-3-one	IC50	3500 nM	US-9187397: Therapeutic curcumin derivatives
(1E,4E)-1,5-bis(2-hydroxyphenyl)penta-1,4-dien-3-one	IC50	4200 nM	US-9187397: Therapeutic curcumin derivatives
2,6-Bis-[1-(4-hydroxy-3-methoxy-phenyl)-meth-(E)-ylidene]-cyclohexanone	IC50	4200 nM	US-9187397: Therapeutic curcumin derivatives
(1E,4E)-1,5-bis[2-(trifluoromethyl)phenyl]penta-1,4-dien-3-one	IC50	5000 nM	US-9187397: Therapeutic curcumin derivatives
9-chloro-8-(3-methylbutoxy)-1,4a,5,5a,6,7,8,9,9a,10a-decahydrochromeno[2,3-d]pyrimidine-2,4-dione	IC50	5000 nM	US-10226464: Small molecule NF-κB inhibitors
[4-[(1E,4E)-5-(4-acetyloxy-3-methoxyphenyl)-3-oxopenta-1,4-dienyl]-2-methoxyphenyl] acetate	IC50	5400 nM	US-9187397: Therapeutic curcumin derivatives
(1E,4E)-1,5-bis(2,5-dimethoxyphenyl)penta-1,4-dien-3-one	IC50	6400 nM	US-9187397: Therapeutic curcumin derivatives
(1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-methylhepta-1,4,6-trien-3-one	IC50	6700 nM	US-9187397: Therapeutic curcumin derivatives
8-methyl-1,4a,5,5a,6,7,8,9,9a,10a-decahydrochromeno[2,3-d]pyrimidine-2,4-dione	IC50	7000 nM	US-10226464: Small molecule NF-κB inhibitors
(1E,4Z,6E)-4-benzyl-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one	IC50	7600 nM	US-9187397: Therapeutic curcumin derivatives
(1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one	IC50	8200 nM	US-9187397: Therapeutic curcumin derivatives
6,8-dimethoxy-1,4a,5,5a,6,7,8,9,9a,10a-decahydrochromeno[2,3-d]pyrimidine-2,4-dione	IC50	8200 nM	US-10226464: Small molecule NF-κB inhibitors
8-ethoxy-1,4a,5,5a,6,7,8,9,9a,10a-decahydrochromeno[2,3-d]pyrimidine-2,4-dione	IC50	9000 nM	US-10226464: Small molecule NF-κB inhibitors
6,8-dimethoxy-2-sulfanylidene-1,4a,5,5a,6,7,8,9,9a,10a-decahydrochromeno[2,3-d]pyrimidin-4-one	IC50	10000 nM	US-10226464: Small molecule NF-κB inhibitors
8-(3,3-dimethylbutoxy)-7-fluoro-1,4a,5,5a,6,7,8,9,9a,10a-decahydrochromeno[2,3-d]pyrimidine-2,4-dione	IC50	10000 nM	US-10226464: Small molecule NF-κB inhibitors
(1E,6E)-1-[4-hydroxy-3-(hydroxymethyl)phenyl]-7-(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	IC50	85000 nM	US-9187406: Curcumin analogues as zinc chelators and their uses

ChEMBL bioactivities

1821 potent at pChembl≥5 of 2385 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
8.55	Potency	2.8	nM	CHEMBL1368961
8.55	Potency	2.8	nM	CHEMBL1413401
8.55	Potency	2.8	nM	AZELAIC ACID
8.52	IC50	3	nM	CHEMBL337665
8.49	Potency	3.2	nM	SALIRASIB
8.46	Potency	3.5	nM	CHEMBL1373139
8.46	Potency	3.5	nM	CHEMBL1437832
8.46	Potency	3.5	nM	CHEMBL1413401
8.46	Potency	3.5	nM	HOMOVANILLIC ACID
8.46	Potency	3.5	nM	PIMAGEDINE
8.46	Potency	3.5	nM	CHEMBL1317446
8.46	Potency	3.5	nM	CHEMBL1521453
8.46	Potency	3.5	nM	NALIDIXATE SODIUM
8.46	Potency	3.5	nM	CHEMBL2062342
8.46	Potency	3.5	nM	CHEMBL1492473
8.40	Potency	4	nM	CHEMBL1448859
8.30	Potency	5	nM	CHEMBL1607062
8.21	IC50	6.2	nM	IXAZOMIB
8.20	Potency	6.3	nM	SALAGEN
8.20	Potency	6.3	nM	1-METHYLIMIDAZOLE
8.15	Potency	7.1	nM	DEPHOSTATIN
8.10	IC50	8	nM	AS-602868
8.10	Potency	7.9	nM	CHEMBL1360725
8.10	Potency	7.9	nM	CHEMBL1496514
8.10	Potency	7.9	nM	CHEMBL1336727
8.05	IC50	9	nM	CHEMBL3218828
8.05	IC50	9	nM	CHEMBL3218834
8.05	IC50	9	nM	CHEMBL3218836
8.05	EC50	9	nM	CHEMBL5279887
8.05	Potency	8.9	nM	CHEMBL1320485
8.01	IC50	9.7	nM	BORTEZOMIB
8.00	IC50	10	nM	CHEMBL3218835
8.00	IC50	10	nM	TRIPTOLIDE
8.00	Potency	10	nM	QUISQUALATE
8.00	Potency	10	nM	CHEMBL2373633
8.00	Potency	10	nM	CHEMBL1354141
8.00	Potency	10	nM	CHEMBL1482236
8.00	Potency	10	nM	PHENELZINE
8.00	Potency	10	nM	PIROXICAM
8.00	Potency	10	nM	CHEMBL1592340
7.95	Potency	11.2	nM	GLIPIZIDE
7.92	IC50	12	nM	CHEMBL3218824
7.92	IC50	12	nM	CHEMBL3218837
7.90	Potency	12.6	nM	CHEMBL1554789
7.90	Potency	12.6	nM	(S)APOMORPHINE

PubChem BioAssay actives

239 with measured affinity, of 1558 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
(1R,2R,3S,3aR,8bS)-1,8b-dihydroxy-6,8-dimethoxy-3a-(4-methoxyphenyl)-N,N-dimethyl-3-phenyl-2,3-dihydro-1H-cyclopenta[b][1]benzofuran-2-carboxamide	479074: Inhibition of NFkappa p50 isolated from nuclear extract of human HeLa cells assessed as blockade of binding to biotinylated consesus sequence by chemiluminescence assay	ic50	0.0750	uM
(1S,2R,9S,12S)-12-hydroxy-4-methyl-13-methylidenetetracyclo[10.2.1.01,9.03,8]pentadeca-3,5,7-triene-2-carboxylic acid	1725234: Binding affinity to NF-kappaB p50 (unknown origin) by SPR analysis	kd	0.0760	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
butyl 3-[[2-chloro-4-(trifluoromethyl)pyrimidine-5-carbonyl]amino]-5-(trifluoromethyl)benzoate	146672: In vitro inhibitory activity against human Jurkat T-Cells stably transfected with an Nuclear factor kappa B transcription factor	ic50	0.1700	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, increases activity, affects binding, increases localization, affects localization (+6 more)	26
Resveratrol	decreases phosphorylation, decreases activity, increases reaction, affects cotreatment, affects binding (+6 more)	18
Tetradecanoylphorbol Acetate	increases phosphorylation, affects cotreatment, decreases reaction, increases activity, affects binding (+6 more)	18
Hydrogen Peroxide	decreases reaction, increases activity, increases expression, increases localization, affects localization (+3 more)	15
Particulate Matter	decreases expression, affects expression, affects localization, affects binding, decreases reaction (+5 more)	14
Curcumin	affects binding, decreases reaction, increases reaction, affects localization, decreases expression (+3 more)	13
bisphenol A	affects binding, increases reaction, affects localization, increases expression, decreases methylation (+4 more)	12
sodium arsenite	increases expression, increases response to substance, affects expression, affects cotreatment, decreases response to substance (+6 more)	11
Doxorubicin	affects localization, affects cotreatment, affects binding, increases expression, increases localization (+6 more)	11
Arsenic Trioxide	affects localization, affects binding, decreases expression, affects cotreatment, affects expression (+2 more)	9
Vehicle Emissions	increases activity, affects cotreatment, decreases expression, increases reaction, affects binding (+5 more)	7
Okadaic Acid	affects binding, decreases reaction, increases activity	7
3-(4-methylphenylsulfonyl)-2-propenenitrile	affects localization, decreases reaction, increases expression, decreases activity, increases reaction (+1 more)	6
Bortezomib	affects cotreatment, decreases reaction, increases activity, decreases expression, affects binding (+3 more)	6
Acetylcysteine	decreases activity, affects localization, increases expression, decreases expression, decreases reaction	6
Estradiol	increases expression, affects cotreatment, decreases reaction, increases activity, affects binding (+1 more)	6
Asbestos, Crocidolite	increases expression, decreases reaction, affects expression, affects localization, affects binding (+1 more)	6
pyrrolidine dithiocarbamic acid	decreases reaction, increases activity, affects binding	5
Dexamethasone	affects localization, decreases reaction, increases activity, affects binding, increases expression	5
Glucosamine	decreases reaction, increases expression, increases localization, increases degradation	5
Quercetin	decreases phosphorylation, affects cotreatment, decreases expression, affects binding, decreases activity (+3 more)	5
Cadmium Chloride	decreases expression, increases activity, increases expression	5
Aspirin	increases reaction, decreases expression, decreases reaction, increases activity, affects binding	4
Benzo(a)pyrene	increases abundance, affects methylation, increases activity, increases expression, affects cotreatment (+1 more)	4
Cisplatin	affects response to substance, affects expression, decreases response to substance, increases expression, increases localization	4
Glucose	increases expression, increases response to substance, affects cotreatment, decreases reaction	4
Melitten	increases phosphorylation, decreases reaction, increases activity, increases localization, decreases localization	4
Valproic Acid	decreases expression, decreases methylation, increases expression, affects expression, decreases reaction (+2 more)	4
Zinc	affects localization, decreases reaction, decreases expression, affects binding, increases expression (+1 more)	4
Simvastatin	increases localization, affects reaction, decreases activity, decreases reaction, increases activity (+3 more)	4

ChEMBL screening assays

256 unique, capped per target: 249 binding, 7 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

10 cell lines: 9 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7YH	Abcam Raji NFKB1 KO	Cancer cell line	Male
CVCL_B9Z5	Abcam THP-1 NFKB1 KO	Cancer cell line	Male
CVCL_C7AV	Abcam PC-3 NFKB1 KO	Cancer cell line	Male
CVCL_D7VR	Ubigene A-549 NFKB1 KO	Cancer cell line	Male
CVCL_D8R8	Ubigene HCT 116 NFKB1 KO	Cancer cell line	Male
CVCL_D9L8	Ubigene HEK293 NFKB1 KO	Transformed cell line	Female
CVCL_E0J1	Ubigene HeLa NFKB1 KO	Cancer cell line	Female
CVCL_E1EK	Ubigene U-87 MG NFKB1 KO	Cancer cell line	Male
CVCL_TA58	HAP1 NFKB1 (-) 1	Cancer cell line	Male
CVCL_TA59	HAP1 NFKB1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

42 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
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®
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)
NCT00263237	PHASE1	COMPLETED	STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency
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
NCT01196702	Not specified	COMPLETED	Lymphocyte Immunophenotyping in Common Variable Immunodeficiency
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01981785	Not specified	UNKNOWN	Investigation of Immune Disorders and Deficiencies
NCT02960399	Not specified	TERMINATED	Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older
NCT03188419	Not specified	COMPLETED	Breadth of Donor Options for People With Inherited Diseases Requiring Allogeneic Hematopoietic Stem Cell Transplant in the Era of Alternative Donor Transplants Using Post-Transplantation Cyclophosphamide
NCT03211689	Not specified	COMPLETED	The Impact of Exercise on Stress, Fatigue, and Quality of Life in Individuals With Primary Immunodeficiency Disease
NCT03534479	Not specified	COMPLETED	Human IgGs and Endothelial Function in Vivo in Humans
NCT05310604	Not specified	COMPLETED	Early Detection of Primary Antibody Deficiencies in Primary Care Facilities by an Algorithm Driven Selection of Serologic Testing in Individuals at Risk.
NCT05321407	Not specified	ACTIVE_NOT_RECRUITING	COVID-19 Vaccine Responses in PIDD Subjects
NCT05481554	Not specified	UNKNOWN	Composition and Function of Gut Microbiota in Porto-sinusoidal Vascular Disease Associated With Variable Common Immunodeficiency
NCT06145100	Not specified	COMPLETED	Prediction of Portal Hypertension in Patients With CVID (CVID-pHT)