IKBKB

Summary

IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta, HGNC:5960) is a protein-coding gene on chromosome 8p11.21, encoding Inhibitor of nuclear factor kappa-B kinase subunit beta (O14920). Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses.

The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene.

Source: NCBI Gene 3551 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe combined immunodeficiency due to IKK2 deficiency (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 855 total — 19 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_001556

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5960
Approved symbol	IKBKB
Name	inhibitor of nuclear factor kappa B kinase subunit beta
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	IKK2, NFKBIKB, IKK-beta, IKKB
Ensembl gene	ENSG00000104365
Ensembl biotype	protein_coding
OMIM	603258
Entrez	3551

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 14 nonsense_mediated_decay, 13 protein_coding, 11 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000342222, ENST00000416505, ENST00000517388, ENST00000517502, ENST00000517812, ENST00000517890, ENST00000517917, ENST00000518647, ENST00000518679, ENST00000518983, ENST00000519733, ENST00000519735, ENST00000519938, ENST00000520201, ENST00000520655, ENST00000520810, ENST00000520835, ENST00000521225, ENST00000521661, ENST00000522103, ENST00000522133, ENST00000522147, ENST00000522545, ENST00000522785, ENST00000523018, ENST00000523105, ENST00000523517, ENST00000523599, ENST00000629753, ENST00000648136, ENST00000649612, ENST00000649751, ENST00000676525, ENST00000870190, ENST00000870191, ENST00000870192, ENST00000870193, ENST00000870194, ENST00000935692, ENST00000957019, ENST00000957020, ENST00000957021

RefSeq mRNA: 3 — MANE Select: NM_001556 NM_001190720, NM_001242778, NM_001556

CCDS: CCDS55228, CCDS6128

Canonical transcript exons

ENST00000520810 — 22 exons

Exon	Start	End
ENSE00002137134	42271302	42271469
ENSE00003474291	42314322	42314429
ENSE00003490882	42329124	42329214
ENSE00003492987	42288634	42288728
ENSE00003493146	42306343	42306432
ENSE00003505903	42319585	42319646
ENSE00003522256	42272083	42272205
ENSE00003530605	42305187	42305275
ENSE00003560365	42325970	42326097
ENSE00003567384	42316210	42316339
ENSE00003569053	42317657	42317771
ENSE00003578198	42290156	42290273
ENSE00003580491	42322347	42322494
ENSE00003591846	42321896	42321945
ENSE00003599981	42322054	42322153
ENSE00003605669	42319270	42319421
ENSE00003606021	42320735	42320844
ENSE00003607497	42293443	42293512
ENSE00003637482	42318552	42318675
ENSE00003672043	42308901	42309025
ENSE00003693992	42316710	42316904
ENSE00003836465	42330914	42332460

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.0626 / max 206.2583, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88676	15.8765	1808
88677	2.1861	1313

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	96.24	gold quality
granulocyte	CL:0000094	95.98	gold quality
lower esophagus mucosa	UBERON:0035834	95.66	gold quality
right lobe of thyroid gland	UBERON:0001119	95.34	gold quality
right uterine tube	UBERON:0001302	95.16	gold quality
skin of leg	UBERON:0001511	95.13	gold quality
skin of abdomen	UBERON:0001416	95.05	gold quality
minor salivary gland	UBERON:0001830	95.03	gold quality
metanephros cortex	UBERON:0010533	95.02	gold quality
esophagus mucosa	UBERON:0002469	94.99	gold quality
left lobe of thyroid gland	UBERON:0001120	94.98	gold quality
tonsil	UBERON:0002372	94.91	gold quality
vagina	UBERON:0000996	94.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.71	gold quality
thyroid gland	UBERON:0002046	94.62	gold quality
upper lobe of left lung	UBERON:0008952	94.58	gold quality
lymph node	UBERON:0000029	94.54	gold quality
ectocervix	UBERON:0012249	94.45	gold quality
left uterine tube	UBERON:0001303	94.39	gold quality
body of uterus	UBERON:0009853	94.37	gold quality
urethra	UBERON:0000057	94.33	gold quality
tibial nerve	UBERON:0001323	94.32	gold quality
mouth mucosa	UBERON:0003729	94.27	gold quality
upper lobe of lung	UBERON:0008948	94.22	gold quality
esophagus	UBERON:0001043	94.17	gold quality
mucosa of stomach	UBERON:0001199	94.14	gold quality
fundus of stomach	UBERON:0001160	94.11	gold quality
body of stomach	UBERON:0001161	94.11	gold quality
blood	UBERON:0000178	94.07	gold quality
zone of skin	UBERON:0000014	93.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
CD44	Repression
COMT	Repression
CXCL8	Unknown
HES1	Activation
MMP9	Repression
NOS2	Repression
OPA1	Activation
TP53	Unknown
VCAM1	Repression

Upstream regulators (CollecTRI, top): CEBPB, FOSL1, HIF1A, IRF6, JUN, MYC, NFE2L2, NFKBIA, NFKBIB, NKX2-1, RELA, RUNX3, SP1, TXK

miRNA regulators (miRDB)

79 targeting IKBKB, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703

Literature-anchored findings (GeneRIF, showing 40)

• difference of kinetic mechanisms of heterodimer with IKK-1 compared with IKK and TBK-1 (PMID:11815618)
• IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. (PMID:11839743)
• Tnf-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. (PMID:11864612)
• Endothelial IKK beta signaling is required for monocyte adhesion under laminar flow conditions. (PMID:11945026)
• Hyperoxia prolongs tumor necrosis factor-alpha-mediated activation of NF-kappaB: role of IkappaB kinase. (PMID:11954826)
• FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress. (PMID:12210728)
• results demonstrate that IKK2 is essential for dendritic cell activation induced by CD40L or contact with allogeneic T cells, but not by LPS, whereas NIK is not required for any of these signals (PMID:12393548)
• activity is comparable in normal B cells and B-CLL lymphocytes and is not involved in up-regulation of TRAF1 in B-CLL (PMID:12411322)
• TNFalpha activation of the NF-kappaB pathway is associated with the inducible binding of TAK1 to TRAF2 and both IKKalpha and IKKbeta (PMID:12547194)
• IKKalpha and IKKbeta may alter their substrate and signaling specificities to regulate mitogen-induced DNA synthesis through distinct mechanisms (PMID:12589056)
• identified the alpha-chain of the GMCSF receptor as interaction partner of IkappaB kinase beta; direct interaction of IKKbeta and GMRalpha in cells was verified. (PMID:12637324)
• IKKbeta has a role in TNFalpha-induced ICAM-1 expression (PMID:12645577)
• identification of inducible phosphoacceptors in IKKgamma/NEMO subunit (PMID:12657630)
• IkappaB and NF-kappaB are substrates for the IKK complex in the activation of NF-kappaB (PMID:12842894)
• ligand-induced homotypic interactions between IKKbeta molecules result in IKKbeta phosphorylation and consequently IKK activation (PMID:12890679)
• determination of signal induced ubiquitination (PMID:14514672)
• noncoordinate expression of I kappa B kinases plays a role in determining the cell type-specific role of Akt in NF-kappa B activation. (PMID:14585846)
• PP2Cbeta down-regulates cytokine-induced NF-kappaB activation by altering IKK activity. (PMID:14585847)
• IKBK has a role in CXCL16 signaling that induces cell-cell adhesion and aortic smooth muscle cell proliferation (PMID:14625285)
• Virtually all TNF-alpha-inducible genes were dependent on I kappa B kinase 2 (IKK2)/NF-kappa B activation, whereas a minor number was additionally modulated by p38; genes suppressed by IKK2/NF-kappa B were newly identified (PMID:14715628)
• required for Human Cytomegalovirus-induced NF-kappaB activation, as well as the replication of different HCMV strains (PMID:14990741)
• Phosphorylation of serine 536, the main T-cell-inducible phosphorylation site of the NF-kappa B p65 subunit, is mediated by IKK beta and occurs within the cytosolic p50/p65/I kappa B alpha complex. (PMID:15128824)
• NF-kappaB-inducing kinase induces p100 processing by docking IkappaB kinase alpha (IKKalpha) to p100 (PMID:15140882)
• NF-kappaB dysregulation and uPA overexpression have roles in a more aggressive tumor behavior in hepatocellular carcinoma, and IKKbeta plays a critical role in the HBx-activated NF-kappaB signaling pathway (PMID:15217951)
• IKKbeta-IKKgamma complexes are involved in mainstream NF-kappaB activation cascades because they can be activated by tumor necrosis factor (PMID:15226300)
• IkappaBalpha kinase beta is inhibited by dehydroascorbic acid (PMID:15254232)
• Ubiquitin-like domain as a critical functional domain specific for IKKbeta that might play a role in dissociating IKKbeta from p65. (PMID:15319427)
• IL-1-inducible phosphorylation of p65 NFkB is mediated by multiple protein kinases including IKKalpha, IKKbeta, IKKepsilon, TBK1, and an unknown kinase and couples p65 to TAFII31-mediated IL-8 transcription (PMID:15489227)
• activation through a proteasome-independent mechanism via effect of TIFA on TRAF6 (PMID:15492226)
• IKK-beta/NF-kappa B transcription pathway is a key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and skeletal muscle (PMID:15564333)
• results identify IKK as an important factor in triggering influenza virus-induced inflammatory reactions in pulmonary epithelium (PMID:15837793)
• Allogenic dendritic cells, rendered immature by IKK2 transfection, induce in vitro differentiation of naive T cells into CD4+ T-regulatory cells which might prevent graft rejection. (PMID:15880043)
• NIBP is a NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation (PMID:15951441)
• IKKbeta phosphorylates multiple p65 sites, as well as in an IkappaB-p65 complex, and S468 phosphorylation slightly reduces TNF-alpha- and IL-1beta-induced NF-kappaB activation (PMID:16046471)
• Ser15 phosphorylation is important in regulating the oncogenic function of mutant p53 apoptosis induction in the context of the NF-kappaB/IkappaB signaling pathway (PMID:16082226)
• IKKbeta has an important role in TNF-alpha-mediated mucus production in airway epithelium in vitro and in vivo (PMID:16123045)
• PP2A plays a positive rather than a negative role in the regulation of IKKbeta (PMID:16126728)
• results indicate that 3-phosphoinositide-dependent protein kinase-1 is a critical regulator of cell survival by modulating the IkappaB kinase (IKK)/nuclear factor-kappaB pathway (PMID:16207722)
• chronic phosphorylation of IKKbeta at Ser-177/Ser-181 leads to monoubiquitin attachment at nearby Lys-163, which in turn modulates the phosphorylation status of IKKbeta at select C-terminal serines (PMID:16267042)
• LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway) (PMID:16280329)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ikbkb	ENSDARG00000079123
mus_musculus	Ikbkb	ENSMUSG00000031537
rattus_norvegicus	Ikbkb	ENSRNOG00000019073
drosophila_melanogaster	IKKbeta	FBGN0024222

Paralogs (3): TBK1 (ENSG00000183735), CHUK (ENSG00000213341), IKBKE (ENSG00000263528)

Protein

Protein identifiers

Inhibitor of nuclear factor kappa-B kinase subunit beta — O14920 (reviewed: O14920)

Alternative names: I-kappa-B kinase 2, Nuclear factor NF-kappa-B inhibitor kinase beta, Serine/threonine protein kinase IKBKB

All UniProt accessions (13): O14920, A0A499FJS7, A0A7I2V4L0, A0A7P0NCV2, A0A7P0SVL5, E5RFG5, E5RFT3, E5RGA0, E5RGW5, E5RIW0, E5RJH2, G3V105, J3KNS5

UniProt curated annotations — full annotation on UniProt →

Function. Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1. Phosphorylates RIPK1 at ‘Ser-25’ which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus. Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at ‘Thr-749’ which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses. IKBKB-mediated phosphorylation of STAT1 at ‘Thr-749’ promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6. It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription.

Subunit / interactions. Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1 through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts with TICAM1. Interacts with FAF1; the interaction disrupts the IKK complex formation. Interacts with ATM. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with TRIM21. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity. Interacts with PDPK1. Interacts with EIF2AK2/PKR. The phosphorylated form interacts with PPM1A and PPM1B. Interacts with ZNF268 isoform 2; the interaction is further increased in a TNF-dependent manner. Interacts with IKBKE. Interacts with AKAP13. Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation. Interacts with LRRC14; disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core complex formation and leading to a decrease of IKBKB phosphorylation and NF-kappaB activation. Interacts with SASH1. Interacts with ARFIP2. Interacts with FKBP5. Interacts with kinase TBK1; the complex interacts with STAT1, leading to phosphorylation of STAT1 on ‘Thr-749’ by IKBKB. (Microbial infection) Interacts with Yersinia YopJ. (Microbial infection) Interacts with vaccinia virus protein B14.

Subcellular location. Cytoplasm. Nucleus. Membrane raft.

Tissue specificity. Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.

Post-translational modifications. Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity. Phosphorylated by MAP3K7/TAK1 in response to NOD1 and NOD2 signaling, promoting activation and phosphorylation of NF-kappa-B inhibitors, leading to NF-kappa-B activation. Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response. Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription. Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B. (Microbial infection) Acetylation of Thr-180 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway. Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. According to PubMed:19675099, ‘Ser-163’ does not serve as a monoubiquitination site. According to PubMed:16267042, ubiquitination on ‘Ser-163’ modulates phosphorylation on C-terminal serine residues. (Microbial infection) Monoubiquitination by TRIM21 is disrupted by Yersinia YopJ. Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappa-B.

Disease relevance. Immunodeficiency 15B (IMD15B) [MIM:615592] An autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T-cells, and impaired differentiation and activation of immune cells. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 15A (IMD15A) [MIM:618204] An autosomal dominant primary immunodeficiency disorder characterized by lymphopenia, inflammation and immune activation of both CD4+ and CD8+ T cells. Patients suffer from recurrent respiratory tract infections, oral candidiasis, and otitis media. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O14920-1	1	yes
O14920-2	2
O14920-3	3
O14920-4	4

RefSeq proteins (3): NP_001177649, NP_001229707, NP_001547* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR022007	IKKbetaNEMObind	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR041185	IKBKB_SDD	Domain
IPR046375	IKBKB_SDD_sf	Homologous_superfamily
IPR051180	IKK	Family

Pfam: PF00069, PF12179, PF18397

Enzyme classification (BRENDA):

• EC 2.7.11.10 — IkappaB kinase (BRENDA: 7 organisms, 122 substrates, 335 inhibitors, 1 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 3 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-seryl-[I-kappa-B protein] + ATP = O-phospho-L-seryl-[I-kappa-B protein] + ADP + H(+) (RHEA:19073)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (99 total): helix 25, modified residue 18, strand 13, mutagenesis site 11, turn 9, sequence variant 8, splice variant 4, region of interest 3, binding site 2, chain 1, domain 1, cross-link 1, compositionally biased region 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3BRV	X-RAY DIFFRACTION	2.2
3BRT	X-RAY DIFFRACTION	2.25
4KIK	X-RAY DIFFRACTION	2.83
4E3C	X-RAY DIFFRACTION	3.98
8OMV	X-RAY DIFFRACTION	4.16

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14920-F1	87.09	0.70

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): 145 (proton acceptor)

Ligand- & substrate-binding residues (2): 21–29; 44

Post-translational modifications (19): 179, 180, 181, 191, 670, 672, 675, 675, 682, 689, 692, 695, 697, 705, 733, 740, 750, 163, 177

Mutagenesis-validated functional residues (11):

Position	Phenotype
44	loss of kinase activity and no effect on binding to nik. does not phosphorylate stat1 at ’thr-749’.
163	monoubiquitinated; when associated with e-177 and e-181.
166	loss of protein kinase activity.
171	increased activation of nf-kappa-b signaling.
177–181	complete loss of tbk1-mediated phosphorylation.
177	decrease of activity.
177	full activation. interaction with trim21 is enhanced; when associated with e-181. monoubiquitinated; when associated wit
181	decrease of activity.
181	full activation. interaction with trim21 is enhanced; when associated with e-177. monoubiquitinated; when associated wit
191	loss of hypoxic inducibility.
272–756	loss of activation of nf-kappa-b signaling.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1236974	ER-Phagosome pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476	RIP-mediated NFkB activation via ZBP1
R-HSA-202424	Downstream TCR signaling
R-HSA-209543	p75NTR recruits signalling complexes
R-HSA-209560	NF-kB is activated and signals survival
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5602636	IKBKB deficiency causes SCID
R-HSA-5603027	IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
R-HSA-5603029	IkBA variant leads to EDA-ID
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5684264	MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-9020702	Interleukin-1 signaling
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-933543	NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-937039	IRAK1 recruits IKK complex
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975144	IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
R-HSA-9758274	Regulation of NF-kappa B signaling
R-HSA-9833482	PKR-mediated signaling
R-HSA-9860276	SLC15A4:TASL-dependent IRF5 activation
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-9909505	Modulation of host responses by IFN-stimulated genes

MSigDB gene sets: 574 (showing top): PID_BCR_5PATHWAY, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, ATF_B, BIOCARTA_TNFR2_PATHWAY, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, BIOCARTA_RELA_PATHWAY, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE

GO Biological Process (38): stimulatory C-type lectin receptor signaling pathway (GO:0002223), antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent (GO:0002479), MyD88-dependent toll-like receptor signaling pathway (GO:0002755), protein phosphorylation (GO:0006468), autophagy (GO:0006914), inflammatory response (GO:0006954), integrin-mediated signaling pathway (GO:0007229), canonical NF-kappaB signal transduction (GO:0007249), response to virus (GO:0009615), negative regulation of autophagy (GO:0010507), regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803), peptidyl-serine phosphorylation (GO:0018105), tumor necrosis factor-mediated signaling pathway (GO:0033209), regulation of toll-like receptor signaling pathway (GO:0034121), toll-like receptor 3 signaling pathway (GO:0034138), TRIF-dependent toll-like receptor signaling pathway (GO:0035666), Fc-epsilon receptor signaling pathway (GO:0038095), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), T cell receptor signaling pathway (GO:0050852), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), stress-activated MAPK cascade (GO:0051403), protein maturation (GO:0051604), interleukin-1-mediated signaling pathway (GO:0070498), cellular response to tumor necrosis factor (GO:0071356), protein localization to plasma membrane (GO:0072659), negative regulation of cytokine production involved in inflammatory response (GO:1900016), regulation of establishment of endothelial barrier (GO:1903140), negative regulation of bicellular tight junction assembly (GO:1903347), protein polyubiquitination (GO:0000209), pattern recognition receptor signaling pathway (GO:0002221), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of macromolecule metabolic process (GO:0010604), signal transduction involved in regulation of gene expression (GO:0023019), non-canonical NF-kappaB signal transduction (GO:0038061), negative regulation of canonical NF-kappaB signal transduction (GO:0043124)

GO Molecular Function (15): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), IkappaB kinase activity (GO:0008384), protein kinase binding (GO:0019901), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), scaffold protein binding (GO:0097110), protein serine kinase activity (GO:0106310), transferrin receptor binding (GO:1990459), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), IkappaB kinase complex (GO:0008385), cytoplasmic side of plasma membrane (GO:0009898), CD40 receptor complex (GO:0035631), membrane raft (GO:0045121), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Diseases associated with the TLR signaling cascade	3
Toll Like Receptor 3 (TLR3) Cascade	2
p75NTR signals via NF-kB	2
Interleukin-1 signaling	2
TNF signaling	2
DDX58/IFIH1-mediated induction of interferon-alpha/beta	2
Downstream signaling events of B Cell Receptor (BCR)	1
Antigen processing-Cross presentation	1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
ZBP1(DAI) mediated induction of type I IFNs	1
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
toll-like receptor signaling pathway	2
protein kinase activity	2
protein binding	2
protein dimerization activity	2
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
antigen processing and presentation of exogenous peptide antigen via MHC class I	1
phosphorylation	1
protein modification process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
defense response	1
cell surface receptor signaling pathway	1
intracellular signaling cassette	1
response to other organism	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of cytokine-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
protein phosphorylation	1
peptidyl-serine modification	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
regulation of pattern recognition receptor signaling pathway	1
endolysosomal toll-like receptor signaling pathway	1
MyD88-independent toll-like receptor signaling pathway	1
Fc receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1

Protein interactions and networks

STRING

4414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IKBKB	IKBKG	Q9Y6K9	999
IKBKB	TRAF6	Q9Y4K3	996
IKBKB	NFKBIA	P25963	995
IKBKB	CHUK	O15111	983
IKBKB	KEAP1	Q14145	983
IKBKB	NFKB1	P19838	979
IKBKB	ERC1	Q8IUD2	977
IKBKB	RELA	Q04206	957
IKBKB	TNF	P01375	934
IKBKB	HSP90AA1	P07900	933
IKBKB	TAB1	Q15750	920
IKBKB	MUC1	P13931	916
IKBKB	MYOM2	P54296	915
IKBKB	TBK1	Q9UHD2	912
IKBKB	HSP90AB1	P08238	910

IntAct

300 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
IKBKG	IKBKB	psi-mi:“MI:0407”(direct interaction)	0.980
IKBKG	IKBKB	psi-mi:“MI:0915”(physical association)	0.980
IKBKB	IKBKG	psi-mi:“MI:0915”(physical association)	0.980
IKBKB	NFKBIA	psi-mi:“MI:0217”(phosphorylation reaction)	0.970
NFKBIA	IKBKB	psi-mi:“MI:0217”(phosphorylation reaction)	0.970
NFKBIA	IKBKB	psi-mi:“MI:0407”(direct interaction)	0.970

BioGRID (707): MTOR (Affinity Capture-Western), IKBKB (Affinity Capture-Western), IKBKB (Affinity Capture-Western), NFKBIA (Biochemical Activity), RELA (Biochemical Activity), IKBKB (Co-purification), Snap23 (Biochemical Activity), Snap23 (Affinity Capture-Western), IKBKB (Affinity Capture-Western), NFKBIA (Biochemical Activity), IKBKB (Affinity Capture-Western), IKBKB (Affinity Capture-Western), IKBKB (Reconstituted Complex), IKBKB (Affinity Capture-Western), IKBKB (Reconstituted Complex)

ESM2 similar proteins: A2CI34, A2CI35, O14920, O15111, O18412, O43149, O88351, O93307, P29597, P52333, Q09178, Q13049, Q20CR4, Q28DZ1, Q4G3H4, Q4TVR5, Q4VSN1, Q4VSN2, Q4VSN3, Q4VSN4, Q4VSN5, Q5RBH9, Q5SSH7, Q5U464, Q5ZJB4, Q60680, Q62137, Q63272, Q67E00, Q67E01, Q6GM53, Q6XUX0, Q6XUX1, Q6XUX2, Q6XUX3, Q6ZWQ0, Q8BMQ2, Q8BP74, Q8BUI3, Q8CH72

Diamond homologs: A0A509AQE6, A0A5K1K8H0, A2QHV0, A8WYE4, A8XQD5, D3ZHP7, F4I1N8, F4IRW0, F4JBP3, G5EGQ3, I1RNG8, O08678, O08679, O14920, O15111, O15865, O22932, O43293, O54784, O61267, O70150, O70405, O75385, O88351, O88764, O96017, P07313, P20689, P25323, P27448, P32866, P34101, P34947, P35465, P40376, P43249, P51957, P54739, Q03141, Q08E52

SIGNOR signaling

152 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	IKBKB	phosphorylation
IKBKB	“down-regulates activity”	NFKB1	phosphorylation
MAP3K7	“up-regulates activity”	IKBKB	phosphorylation
CASP3	down-regulates	IKBKB	cleavage
TBK1	up-regulates	IKBKB	binding
IKBKB	down-regulates	FOXO3	phosphorylation
IKBKB	“up-regulates activity”	RELA	phosphorylation
IKBKB	up-regulates	DOK1	phosphorylation
IKBKB	down-regulates	YWHAB	phosphorylation
IKBKB	down-regulates	TSC1	phosphorylation
IKBKB	unknown	IKBKG	phosphorylation
IKBKB	“down-regulates activity”	IKBKG	phosphorylation
IKBKB	down-regulates	CDKN2A	phosphorylation
IKBKB	“form complex”	IKK-complex	binding
IKBKG	“up-regulates activity”	IKBKB	binding
PRKAA2	up-regulates	IKBKB	phosphorylation
PPM1A	down-regulates	IKBKB	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 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
RIP-mediated NFkB activation via ZBP1	8	72.6×	4e-11
TRAF6 mediated NF-kB activation	7	43.2×	1e-08
Regulation of NF-kappa B signaling	5	42.9×	3e-06
RHO GTPases activate IQGAPs	8	37.4×	3e-09
TAK1-dependent IKK and NF-kappa-B activation	9	36.5×	4e-10
TCR signaling	5	33.5×	9e-06
Gap junction trafficking and regulation	5	32.1×	1e-05
Gap junction trafficking	5	32.1×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	7	74.7×	1e-09
interleukin-1-mediated signaling pathway	5	50.8×	7e-06
canonical NF-kappaB signal transduction	10	46.4×	1e-11
protein refolding	5	39.5×	2e-05
toll-like receptor 4 signaling pathway	5	33.3×	4e-05
tumor necrosis factor-mediated signaling pathway	6	25.1×	2e-05
negative regulation of canonical NF-kappaB signal transduction	9	19.6×	2e-07
JNK cascade	5	17.2×	6e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PCM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	15
Uncertain significance	280
Likely benign	449
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
102445	NM_001556.3(IKBKB):c.1292dup (p.Gln432fs)	Pathogenic
1357742	NM_001556.3(IKBKB):c.163C>T (p.Arg55Ter)	Pathogenic
1388684	NM_001556.3(IKBKB):c.1927_1928del (p.Val643fs)	Pathogenic
1433844	NM_001556.3(IKBKB):c.1705G>T (p.Glu569Ter)	Pathogenic
1451255	NM_001556.3(IKBKB):c.1731dup (p.Pro578fs)	Pathogenic
1453689	NM_001556.3(IKBKB):c.25del (p.Thr9fs)	Pathogenic
157663	NM_001556.3(IKBKB):c.814C>T (p.Arg272Ter)	Pathogenic
2080261	NM_001556.3(IKBKB):c.1609del (p.Arg536_Met537insTer)	Pathogenic
2096950	NM_001556.3(IKBKB):c.1762C>T (p.Gln588Ter)	Pathogenic
2131114	NM_001556.3(IKBKB):c.1392C>A (p.Cys464Ter)	Pathogenic
2696833	NM_001556.3(IKBKB):c.1696C>T (p.Gln566Ter)	Pathogenic
2768865	NM_001556.3(IKBKB):c.2116del (p.Glu706fs)	Pathogenic
2844327	NM_001556.3(IKBKB):c.1847_1848del (p.Val616fs)	Pathogenic
2856021	NM_001556.3(IKBKB):c.1429C>T (p.Gln477Ter)	Pathogenic
3006118	NM_001556.3(IKBKB):c.1735C>T (p.Arg579Ter)	Pathogenic
3245532	NC_000008.10:g.(?42146132)(42146266_?)del	Pathogenic
4733563	NM_001556.3(IKBKB):c.1273C>T (p.Gln425Ter)	Pathogenic
590941	NM_001556.3(IKBKB):c.607G>A (p.Val203Ile)	Pathogenic
957808	NM_001556.3(IKBKB):c.856C>T (p.Arg286Ter)	Pathogenic
1683291	NM_001556.3(IKBKB):c.2205+2T>C	Likely pathogenic
1878265	NM_001556.3(IKBKB):c.1673del (p.Gly558fs)	Likely pathogenic
2632828	NM_001556.3(IKBKB):c.11C>A (p.Ser4Ter)	Likely pathogenic
2636460	NM_001556.3(IKBKB):c.1241-2A>C	Likely pathogenic
2658583	NM_001556.3(IKBKB):c.477+2T>C	Likely pathogenic
2749018	NM_001556.3(IKBKB):c.1365-2A>C	Likely pathogenic
3064957	NM_001556.3(IKBKB):c.923dup (p.Asn308fs)	Likely pathogenic
3384120	NM_001556.3(IKBKB):c.849G>A (p.Trp283Ter)	Likely pathogenic
3595616	NM_001556.3(IKBKB):c.229C>T (p.Arg77Ter)	Likely pathogenic
3651056	NM_001556.3(IKBKB):c.567+1G>A	Likely pathogenic
3779760	NM_001556.3(IKBKB):c.2115-1G>A	Likely pathogenic

SpliceAI

3966 predictions. Top by Δscore:

Variant	Effect	Δscore
8:42272081:A:AG	acceptor_gain	1.0000
8:42272082:G:GG	acceptor_gain	1.0000
8:42272082:GA:G	acceptor_gain	1.0000
8:42272082:GAGTT:G	acceptor_gain	1.0000
8:42290152:CTA:C	acceptor_loss	1.0000
8:42290154:A:AG	acceptor_gain	1.0000
8:42290154:A:C	acceptor_loss	1.0000
8:42290154:AG:A	acceptor_gain	1.0000
8:42290154:AGGCT:A	acceptor_gain	1.0000
8:42290155:G:GA	acceptor_gain	1.0000
8:42290155:GG:G	acceptor_gain	1.0000
8:42290155:GGC:G	acceptor_gain	1.0000
8:42290155:GGCT:G	acceptor_gain	1.0000
8:42290155:GGCTG:G	acceptor_gain	1.0000
8:42290271:AAG:A	donor_loss	1.0000
8:42290273:GGTG:G	donor_loss	1.0000
8:42290274:G:T	donor_loss	1.0000
8:42305185:A:AG	acceptor_gain	1.0000
8:42305186:G:GG	acceptor_gain	1.0000
8:42305272:GAGG:G	donor_gain	1.0000
8:42305274:GG:G	donor_gain	1.0000
8:42305275:GG:G	donor_gain	1.0000
8:42305276:G:C	donor_loss	1.0000
8:42305277:T:A	donor_loss	1.0000
8:42306341:A:AG	acceptor_gain	1.0000
8:42306342:G:GG	acceptor_gain	1.0000
8:42306342:GTT:G	acceptor_gain	1.0000
8:42306342:GTTA:G	acceptor_gain	1.0000
8:42309022:AGTGG:A	donor_loss	1.0000
8:42309023:GTG:G	donor_gain	1.0000

AlphaMissense

4983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:42272143:T:A	W15R	1.000
8:42272143:T:C	W15R	1.000
8:42272164:G:A	G22R	1.000
8:42272164:G:C	G22R	1.000
8:42272164:G:T	G22W	1.000
8:42272165:G:A	G22E	1.000
8:42272165:G:T	G22V	1.000
8:42272170:G:A	G24R	1.000
8:42272170:G:C	G24R	1.000
8:42272170:G:T	G24W	1.000
8:42272171:G:A	G24E	1.000
8:42272171:G:T	G24V	1.000
8:42272174:G:A	G25E	1.000
8:42272176:T:A	F26I	1.000
8:42272176:T:C	F26L	1.000
8:42272176:T:G	F26V	1.000
8:42272177:T:C	F26S	1.000
8:42272177:T:G	F26C	1.000
8:42272178:T:A	F26L	1.000
8:42272178:T:G	F26L	1.000
8:42272179:G:A	G27R	1.000
8:42272179:G:C	G27R	1.000
8:42272180:G:A	G27E	1.000
8:42272180:G:T	G27V	1.000
8:42272186:T:A	V29D	1.000
8:42272194:T:A	W32R	1.000
8:42272194:T:C	W32R	1.000
8:42288653:C:A	A42D	1.000
8:42288658:A:C	K44Q	1.000
8:42288658:A:G	K44E	1.000

dbSNP variants (sampled 300 via entrez): RS1000021730 (8:42316522 A>G,T), RS1000025454 (8:42282403 T>C), RS1000073103 (8:42324637 A>C,T), RS1000141290 (8:42282713 C>T), RS1000145203 (8:42326420 G>A), RS1000248065 (8:42288856 G>A), RS1000336379 (8:42297546 G>T), RS1000366177 (8:42287981 G>A), RS1000390541 (8:42276764 G>A), RS1000408400 (8:42300542 T>C), RS1000474651 (8:42275222 T>C), RS1000534905 (8:42287252 T>C,G), RS1000535923 (8:42287501 A>C), RS1000562997 (8:42293676 A>G), RS1000588352 (8:42271207 G>A,T)

Disease associations

OMIM: gene MIM:603258 | disease phenotypes: MIM:615592, MIM:618204, MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 15a	Strong	Autosomal recessive
severe combined immunodeficiency due to IKK2 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
immunodeficiency 15a	Moderate	AD
severe combined immunodeficiency due to IKK2 deficiency	Definitive	AR

Mondo (4): severe combined immunodeficiency due to IKK2 deficiency (MONDO:0014267), immunodeficiency 15a (MONDO:0032599), severe combined immunodeficiency (MONDO:0015974), Hirschsprung disease (MONDO:0018309)

Orphanet (4): Combined immunodeficiency due to IKBKB deficiency (Orphanet:397787), Combined immunodeficiency due to IKBKB gain-of-function mutation (Orphanet:700205), Severe combined immunodeficiency (Orphanet:183660), Hirschsprung disease (Orphanet:388)

HPO phenotypes

24 total (25 of 24 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000403	Recurrent otitis media
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0002028	Chronic diarrhea
HP:0002205	Recurrent respiratory infections
HP:0002719	Recurrent infections
HP:0002721	Immunodeficiency
HP:0002728	Chronic mucocutaneous candidiasis
HP:0003593	Infantile onset
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0004432	Agammaglobulinemia
HP:0005415	Decreased CD8+ T cell proportion
HP:0009098	Chronic oral candidiasis
HP:0011108	Recurrent sinusitis
HP:0011463	Childhood onset
HP:0012311	Increased total monocyte count
HP:0030374	Decreased proportion of memory B cells
HP:0031292	Cutaneous abscess
HP:0031381	Decreased mitogen-induced T-cell proliferation
HP:0032218	Decreased CD4+ T cell proportion
HP:0040154	Acne inversa
HP:0040218	Reduced total natural killer cell count
HP:0004430	Severe combined immunodeficiency

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1991 (SINGLE PROTEIN), CHEMBL2111328 (PROTEIN COMPLEX), CHEMBL3883298 (PROTEIN COMPLEX), CHEMBL4523969 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 347,269 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL231884	DIOSMIN	4	4,880
CHEMBL384467	DEXAMETHASONE	4	279,102
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL184041	ERTIPROTAFIB	2	174
CHEMBL363648	TAK-715	2	442
CHEMBL475251	R-406	2	762
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL129857	AS-602868	1	93
CHEMBL1908397	KW-2449	1	622
CHEMBL536151	IMD-0354	1	469
CHEMBL574738	AST-487	1	451

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2272733	Efficacy	3	gefitinib	Exanthema;Non-Small Cell Lung Carcinoma
rs9694958	Toxicity	3	gefitinib	Exanthema;Non-Small Cell Lung Carcinoma

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10958713	IKBKB		0.00	0
rs11986055	IKBKB		0.00	0
rs5029748	IKBKB		0.00	0
rs6474387	IKBKB		0.00	0
rs2272733	IKBKB	3	2.50	1	gefitinib
rs9694958	IKBKB	3	2.00	1	gefitinib

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — IKK family

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
IKK-beta inhibitor R-28	Inhibition	8.1	pIC50
IKK-2 inhibitor IV	Inhibition	7.75	pIC50
BI605906	Inhibition	7.59	pIC50
PHA-408	Inhibition	7.4	pIC50
MLN-120B	Inhibition	7.22	pIC50
BMS-345541	Negative	6.52	pIC50
compound 47 [PMID: 28737909]	Inhibition	5.64	pKi

Binding affinities (BindingDB)

358 measured of 393 human assays (393 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-methoxyindazole-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-4-(methylamino)pyrazolo[4,3-c]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[4-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]-2-pyridinyl]-5-methoxyindazole-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-methoxypyrazolo[5,4-b]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
6-chloro-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[4,3-c]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
8-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyrimidine-6-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
7-cyano-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
7-chloro-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1,7-bis[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-7-methoxyimidazo[1,5-a]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-methoxyimidazo[1,5-a]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-(4-methylimidazol-1-yl)indazole-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
4-(ethylamino)-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[4,3-c]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-methoxypyrazolo[4,3-c]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-methoxypyrazolo[5,4-b]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-methylpyrazolo[5,4-b]pyridine-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
6-fluoro-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]indazole-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
(5R)-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-methyl-5,6-dihydro-4H-cyclopenta[d]pyrazole-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
5-amino-2-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-1,3-thiazole-4-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-(methylamino)pyrazolo[5,4-d][1,3]thiazole-3-carboxamide	KI	0.05 nM	US-9605005: Alkynyl alcohols and methods of use
2-[2-fluoro-5-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-methyl-1,3-thiazole-4-carboxamide	KI	0.053 nM	US-9605005: Alkynyl alcohols and methods of use
6-chloro-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3-carboxamide	KI	0.06 nM	US-9605005: Alkynyl alcohols and methods of use
3-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-(1-methylpyrazol-3-yl)-3H-isoindole-1-carboxamide	KI	0.06 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]indazole-3-carboxamide	KI	0.07 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-(1-methylpyrazol-3-yl)indazole-3-carboxamide	KI	0.07 nM	US-9605005: Alkynyl alcohols and methods of use
5-[1-(2-hydroxyethyl)pyrazol-4-yl]-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]indazole-3-carboxamide	KI	0.07 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[5,4-b]pyridine-3-carboxamide	KI	0.08 nM	US-9605005: Alkynyl alcohols and methods of use
5-fluoro-1-[4-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]-2-pyridinyl]indazole-3-carboxamide	KI	0.08 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-N-methylindazole-3,5-dicarboxamide	KI	0.08 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-(1-methylpyrazol-4-yl)pyrazolo[5,4-b]pyridine-3-carboxamide	KI	0.09 nM	US-9605005: Alkynyl alcohols and methods of use
1-[4-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]-2-pyridinyl]indazole-3-carboxamide	KI	0.098 nM	US-9605005: Alkynyl alcohols and methods of use
6-fluoro-1-[4-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]-2-pyridinyl]indazole-3-carboxamide	KI	0.1 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-(1-methylpyrazol-4-yl)pyrazolo[5,4-b]pyridine-3-carboxamide	KI	0.1 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3,7-dicarboxamide	KI	0.1 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[(3R)-3-hydroxy-3-(5-methyl-1,3,4-oxadiazol-2-yl)but-1-ynyl]phenyl]-7-methoxyimidazo[1,5-a]pyridine-3-carboxamide	KI	0.1 nM	US-9605005: Alkynyl alcohols and methods of use
6-chloro-1-[2-fluoro-5-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3-carboxamide	KI	0.1 nM	US-9605005: Alkynyl alcohols and methods of use
(5S)-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-methyl-5,6-dihydro-4H-cyclopenta[d]pyrazole-3-carboxamide	KI	0.1 nM	US-9605005: Alkynyl alcohols and methods of use
4-(cyclopropylamino)-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[4,3-c]pyridine-3-carboxamide	KI	0.11 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine-3-carboxamide	KI	0.11 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-methoxypyrazolo[3,4-d]pyrimidine-3-carboxamide	KI	0.13 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[5,4-c]pyridazine-3-carboxamide	KI	0.13 nM	US-9605005: Alkynyl alcohols and methods of use
6-fluoro-1-[4-[2-[(7R)-7-hydroxy-5,6-dihydrocyclopenta[b]pyridin-7-yl]ethynyl]-2-pyridinyl]indazole-3-carboxamide	KI	0.14 nM	US-9605005: Alkynyl alcohols and methods of use
7-cyclobutyloxy-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]imidazo[1,5-a]pyridine-3-carboxamide	KI	0.14 nM	US-9605005: Alkynyl alcohols and methods of use
5-bromo-1-[4-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]-2-pyridinyl]indazole-3-carboxamide	KI	0.15 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-7-(trifluoromethyl)imidazo[1,5-a]pyridine-3-carboxamide	KI	0.15 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[3,4-d]pyrimidine-3-carboxamide	KI	0.19 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]pyrazolo[4,3-c]pyridine-3-carboxamide	KI	0.19 nM	US-9605005: Alkynyl alcohols and methods of use
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-5-(3-methoxyazetidin-1-yl)pyrazolo[5,4-b]pyridine-3-carboxamide	KI	0.19 nM	US-9605005: Alkynyl alcohols and methods of use
6-cyclopropyl-1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[3,4-d]pyrimidine-3-carboxamide	KI	0.23 nM	US-9605005: Alkynyl alcohols and methods of use

ChEMBL bioactivities

1417 potent at pChembl≥5 of 1567 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	CHEMBL3897289
10.00	IC50	0.1	nM	CHEMBL5919378
9.70	IC50	0.2	nM	CHEMBL5878871
9.70	IC50	0.2	nM	CHEMBL5883781
9.70	IC50	0.2	nM	CHEMBL5997512
9.40	IC50	0.4	nM	CHEMBL3897289
9.30	IC50	0.5	nM	DEXAMETHASONE
9.30	IC50	0.5	nM	CHEMBL1669569
9.30	IC50	0.5	nM	CHEMBL1669608
9.22	IC50	0.6	nM	CHEMBL5987641
9.22	IC50	0.6	nM	CHEMBL5910422
9.22	IC50	0.6	nM	CHEMBL5869094
9.22	IC50	0.6	nM	CHEMBL1669562
9.22	IC50	0.6	nM	CHEMBL1669563
9.10	IC50	0.8	nM	CHEMBL3915686
9.05	IC50	0.9	nM	STAUROSPORINE
9.05	IC50	0.9	nM	CHEMBL1669599
9.00	IC50	1	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL1669565
9.00	IC50	1	nM	CHEMBL1669605
8.96	IC50	1.1	nM	CHEMBL1669596
8.92	IC50	1.2	nM	CHEMBL1669551
8.89	IC50	1.3	nM	CHEMBL1669597
8.89	IC50	1.3	nM	CHEMBL1669603
8.85	IC50	1.4	nM	CHEMBL1669600
8.80	IC50	1.6	nM	CHEMBL592893
8.72	IC50	1.9	nM	CHEMBL601079
8.72	IC50	1.9	nM	CHEMBL1669571
8.70	Ki	2	nM	CHEMBL516203
8.70	IC50	2	nM	CHEMBL1669601
8.66	IC50	2.2	nM	CHEMBL1669560
8.66	IC50	2.2	nM	CHEMBL1669595
8.64	IC50	2.3	nM	CHEMBL1669602
8.60	IC50	2.512	nM	CHEMBL250105
8.60	IC50	2.5	nM	CHEMBL1669604
8.57	IC50	2.7	nM	CHEMBL5787843
8.55	IC50	2.8	nM	CHEMBL1669559
8.55	IC50	2.8	nM	CHEMBL1669568
8.55	IC50	2.8	nM	CHEMBL1669593
8.52	IC50	3.02	nM	CHEMBL182407
8.52	IC50	3.02	nM	CHEMBL249280
8.52	IC50	3	nM	CHEMBL182407
8.52	IC50	3	nM	CHEMBL249280
8.52	IC50	3	nM	CHEMBL1669552
8.48	IC50	3.3	nM	CHEMBL1669607
8.46	IC50	3.5	nM	CHEMBL1669558
8.46	IC50	3.5	nM	CHEMBL1669554
8.44	IC50	3.6	nM	CHEMBL5910422
8.43	IC50	3.7	nM	CHEMBL1669555
8.42	IC50	3.8	nM	CHEMBL3946903

PubChem BioAssay actives

1417 with measured affinity, of 3868 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
1-[4-[[3-carbamoyl-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]-4-[(1-methylpyrazol-4-yl)methyl]piperazine-2-carboxylic acid	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0005	uM
2-[4-[[4-[4-[[3-carbamoyl-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]piperazin-1-yl]methyl]pyrazol-1-yl]acetic acid	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0005	uM
Dexamethasone	2131647: Inhibition of IKKB (unknown origin)	ic50	0.0005	uM
8-[[5-chloro-2-(4-hydroxypiperidin-1-yl)pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0006	uM
8-[[5-chloro-2-(2-methoxyethylamino)pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0006	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1191826: Inhibition of N-terminal His-tagged recombinant IKK2 (unknown origin) by HTRF assay	ic50	0.0009	uM
8-[[2-[4-[[1-(2-amino-2-oxoethyl)pyrazol-4-yl]methyl]piperazin-1-yl]-5-chloropyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0009	uM
8-[[5-chloro-2-[4-[[1-[2-(2-hydroxyethylamino)-2-oxoethyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0010	uM
ethyl 2-[4-[[4-[4-[[3-carbamoyl-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]piperazin-1-yl]methyl]pyrazol-1-yl]acetate	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0010	uM
methyl 2-[4-[[4-[4-[[3-carbamoyl-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]piperazin-1-yl]methyl]pyrazol-1-yl]acetate	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0011	uM
8-[[5-chloro-2-(4-methylpiperazin-1-yl)pyridine-4-carbonyl]amino]-1-(3-hydroxyphenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0012	uM
2-methoxyethyl 2-[4-[[4-[4-[[3-carbamoyl-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]piperazin-1-yl]methyl]pyrazol-1-yl]acetate	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0013	uM
8-[[5-chloro-2-[4-[[1-[2-(2-methoxyethylamino)-2-oxoethyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0013	uM
8-[[5-chloro-2-[4-[[1-[2-(methylamino)-2-oxoethyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0014	uM
8-[[5-chloro-2-(4-methylpiperazin-1-yl)pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0016	uM
8-[[5-chloro-2-[4-(2-methoxyethyl)piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0019	uM
8-[[5-chloro-2-[4-(1H-pyrazol-4-ylmethyl)piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0019	uM
7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-piperidin-3-yl]-1,4-dihydropyrido[2,3-d][1,3]oxazin-2-one	414513: Inhibition of IKK-beta by TR-FRET assay	ki	0.0020	uM
8-[[5-chloro-2-[4-[[1-[2-oxo-2-(propan-2-ylamino)ethyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0020	uM
1-(4-chloro-3-hydroxyphenyl)-8-[[5-chloro-2-(4-methylpiperazin-1-yl)pyridine-4-carbonyl]amino]-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0022	uM
8-[[5-chloro-2-[4-[[1-(3-hydroxypropyl)pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0022	uM
8-[[5-chloro-2-[4-[[1-[2-(dimethylamino)-2-oxoethyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0023	uM
N’-[12-methyl-4-(1H-pyrrol-2-yl)-3-thia-1,7,10-triazatricyclo[7.3.0.02,6]dodeca-2(6),4,7,9,11-pentaen-8-yl]ethane-1,2-diamine	744273: Inhibition of human IKKbeta using GST-IkappaBalpha as substrate	ic50	0.0025	uM
8-[[5-chloro-2-[4-[[1-[2-(2-methylsulfanylethylamino)-2-oxoethyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0025	uM
8-[[5-chloro-2-[4-[[1-(3-methoxypropyl)pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0028	uM
8-[[5-chloro-2-[4-[(1,5-dimethylpyrazol-4-yl)methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0028	uM
1-(3-chloro-4-hydroxyphenyl)-8-[[5-chloro-2-(4-methylpiperazin-1-yl)pyridine-4-carbonyl]amino]-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0028	uM
2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-3-ylpyridine-3-carbonitrile	241989: Inhibition of recombinant human I-kappa-B-kinase beta (IKK beta)	ic50	0.0030	uM
12-methyl-8-(methylamino)-4-[3-[(sulfamoylamino)methyl]phenyl]-3-thia-1,7,10-triazatricyclo[7.3.0.02,6]dodeca-2(6),4,7,9,11-pentaene	1798611: IKK Inhibition Assay from Article 10.1016/j.bmcl.2007.05.031: “Synthesis and structure-activity relationship of imidazo(1,2-a)thieno(3,2-e)pyrazines as IKK-beta inhibitors.”	ic50	0.0030	uM
8-[[5-chloro-2-[4-[(1-methylpyrazol-4-yl)methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0030	uM
8-[[5-chloro-2-[4-[[1-[2-[3-(dimethylamino)propylamino]-2-oxoethyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0033	uM
8-[[5-chloro-2-[3-methyl-4-[(1-methylpyrazol-4-yl)methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0035	uM
8-[[5-chloro-2-(4-methylpiperazin-1-yl)pyridine-4-carbonyl]amino]-1-(4-hydroxyphenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0035	uM
8-[[5-chloro-2-[4-[[1-[3-(dimethylamino)propyl]pyrazol-4-yl]methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0037	uM
4-[4-[[3-carbamoyl-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]-1-[(1-methylpyrazol-4-yl)methyl]piperazine-2-carboxylic acid	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0039	uM
2-amino-6-[2-(cyclobutylmethoxy)-6-hydroxyphenyl]-4-piperidin-3-ylpyridine-3-carbonitrile	241989: Inhibition of recombinant human I-kappa-B-kinase beta (IKK beta)	ic50	0.0040	uM
4-(2-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-N-(1,1-dioxothian-4-yl)benzenesulfonamide	697979: Inhibition of IKK2 in presence of 1 uM ATP	ic50	0.0040	uM
8-[[5-chloro-2-[4-[(1-ethylpyrazol-4-yl)methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0042	uM
8-[[5-chloro-2-[4-[(1,3-dimethylpyrazol-4-yl)methyl]piperazin-1-yl]pyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0043	uM
ethyl 3-[4-[[4-[4-[[3-carbamoyl-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]piperazin-1-yl]methyl]pyrazol-1-yl]propanoate	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0047	uM
8-[[5-chloro-2-(4-methylpiperazin-1-yl)pyridine-4-carbonyl]amino]-1-(3-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0048	uM
2-amino-6-(2-hydroxy-6-propoxyphenyl)-4-piperidin-3-ylpyridine-3-carbonitrile	241989: Inhibition of recombinant human I-kappa-B-kinase beta (IKK beta)	ic50	0.0050	uM
2-amino-6-[2-hydroxy-6-(2-methylpropoxy)phenyl]-4-piperidin-3-ylpyridine-3-carbonitrile	241989: Inhibition of recombinant human I-kappa-B-kinase beta (IKK beta)	ic50	0.0050	uM
N-[[3-[12-methyl-8-(methylamino)-5-thia-3,7,10,12-tetrazatricyclo[7.3.0.02,6]dodeca-1(9),2(6),3,7,10-pentaen-4-yl]phenyl]methyl]methanesulfonamide	1798905: IKK Enzymatic Activity Assay from Article 10.1021/jm8015816: “Novel tricyclic inhibitors of IkappaB kinase.”	ic50	0.0050	uM
ethyl 2-[4-[[4-[4-[[3-carbamoyl-1-(3-fluorophenyl)-4,5-dihydrobenzo[g]indazol-8-yl]carbamoyl]-5-chloro-2-pyridinyl]piperazin-1-yl]methyl]pyrazol-1-yl]acetate	567900: Inhibition of human recombinant IKK2 in human PBMC	ic50	0.0050	uM
3-(dimethylamino)-N-[[6-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]-2-pyridinyl]methyl]propanamide	631800: Inhibition of human IKK2-mediated GST-IkappaBalpha protein fusion phosphorylation	ic50	0.0050	uM
N-(1,1-dioxothian-4-yl)-4-(2-ethyl-1H-pyrrolo[2,3-b]pyridin-4-yl)benzenesulfonamide	697979: Inhibition of IKK2 in presence of 1 uM ATP	ic50	0.0050	uM
1,3-dimethyl-1-[[6-[3-methyl-7-(methylamino)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-11-yl]-2-pyridinyl]methyl]urea	631800: Inhibition of human IKK2-mediated GST-IkappaBalpha protein fusion phosphorylation	ic50	0.0057	uM
N,12-dimethyl-4-phenyl-5-thia-3,7,10,12-tetrazatricyclo[7.3.0.02,6]dodeca-1(9),2(6),3,7,10-pentaen-8-amine	1798905: IKK Enzymatic Activity Assay from Article 10.1021/jm8015816: “Novel tricyclic inhibitors of IkappaB kinase.”	ic50	0.0060	uM
2-amino-6-(2-hydroxy-6-pentoxyphenyl)-4-piperidin-3-ylpyridine-3-carbonitrile	241989: Inhibition of recombinant human I-kappa-B-kinase beta (IKK beta)	ic50	0.0060	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, increases phosphorylation, increases activity, increases expression, increases reaction	7
sodium arsenite	affects expression, decreases expression, increases activity, increases expression, affects response to substance	5
Curcumin	decreases reaction, increases expression, increases activity, decreases activity, decreases expression	5
bisphenol A	increases expression, decreases reaction, affects cotreatment, decreases expression	4
Arsenic Trioxide	decreases expression, increases expression, increases activity, increases phosphorylation, increases degradation (+2 more)	4
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases phosphorylation, decreases activity, decreases expression, decreases reaction, increases activity	3
Bortezomib	decreases expression, increases reaction, affects reaction, increases degradation, increases phosphorylation	3
Resveratrol	affects cotreatment, increases expression, decreases reaction, decreases phosphorylation	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, increases expression (+2 more)	3
Arsenic	affects methylation, decreases expression	3
Cadmium	increases expression, increases phosphorylation, decreases reaction, affects cotreatment	3
Tetradecanoylphorbol Acetate	decreases reaction, increases activity, increases phosphorylation, increases reaction, increases expression	3
Particulate Matter	affects cotreatment, increases abundance, increases expression	3
arsenite	decreases activity, decreases expression, increases expression, affects binding, decreases reaction (+2 more)	2
nickel chloride	decreases reaction, increases phosphorylation, decreases expression	2
2-((aminocarbonyl)amino)-5-(4-fluorophenyl)-3-thiophenecarboxamide	increases phosphorylation, increases reaction, decreases activity	2
(+)-JQ1 compound	decreases activity, increases reaction, decreases phosphorylation	2
Vorinostat	affects cotreatment, decreases expression, decreases phosphorylation	2
Acetylcysteine	decreases reaction, increases abundance, increases phosphorylation, decreases activity	2
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance, affects metabolic processing	2
Vehicle Emissions	affects cotreatment, increases expression, increases abundance	2
Cisplatin	increases expression, affects response to substance	2
Copper	affects binding, increases expression, decreases activity, decreases response to substance	2
Doxorubicin	increases phosphorylation, decreases reaction, increases degradation, increases reaction	2
Ozone	increases degradation, decreases reaction, affects cotreatment, decreases expression, increases oxidation (+1 more)	2
Plant Extracts	increases expression, decreases reaction, affects cotreatment	2
Quercetin	increases phosphorylation, decreases reaction	2
Zinc	affects expression, affects binding, increases localization, increases expression	2
Simvastatin	decreases reaction, increases phosphorylation, increases reaction, decreases expression	2
Apigenin	decreases phosphorylation, decreases reaction, increases phosphorylation, increases expression, increases activity (+2 more)	2

ChEMBL screening assays

855 unique, capped per target: 839 binding, 11 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003320	Binding	Inhibition of IKK-beta at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1964112	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: IKBKB	PubChem BioAssay data set
CHEMBL4040596	ADMET	Inhibition of IKKbeta in human U2OS cells assessed as TNFalpha induced IkBalpha degradation at 100 uM preincubated for 1 hr followed by TNFalpha stimulation for 30 mins by Western blot analysis	Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1UC	Abcam HeLa IKBKB KO	Cancer cell line	Female
CVCL_D7RW	Ubigene A-549 IKBKB KO	Cancer cell line	Male
CVCL_D8MY	Ubigene HCT 116 IKBKB KO	Cancer cell line	Male
CVCL_D9GV	Ubigene HEK293 IKBKB KO	Transformed cell line	Female
CVCL_E0ES	Ubigene HeLa IKBKB KO	Cancer cell line	Female
CVCL_SS35	HAP1 IKBKB (-) 1	Cancer cell line	Male
CVCL_SS36	HAP1 IKBKB (-) 2	Cancer cell line	Male
CVCL_SS37	HAP1 IKBKB (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	PHASE1/PHASE2	COMPLETED	IMM 0212: Busulfan With Fludarabine and Antithymocyte Globulin as Preparative Therapy for Hematopoietic Stem Cell Transplant for the Treatment of Severe Congenital T-Cell Immunodeficiency
NCT00579137	PHASE1/PHASE2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	PHASE1/PHASE2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	PHASE1/PHASE2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	PHASE1/PHASE2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	PHASE1/PHASE2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT00001255	Not specified	COMPLETED	Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006335	Not specified	COMPLETED	Influences on Female Adolescents’ Decisions Regarding Testing for Carrier Status of XSCID
NCT00055172	Not specified	RECRUITING	Genetic Basis of Immunodeficiency
NCT00695279	Not specified	COMPLETED	Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products
NCT00845416	Not specified	COMPLETED	Newborn Screening for Severe Combined Immunodeficiency (SCID) in a High-Risk Population
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT01953016	Not specified	COMPLETED	Participation in a Research Registry for Immune Disorders
NCT02231983	Not specified	UNKNOWN	Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China