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): 886 total — 19 pathogenic, 18 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 16 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 24
• Drug target: yes — 7 curated mechanism-of-action drugs; 16 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_001556
• Interaction hub: 3,210 STRING partners (top 2% of genes corpus-wide)

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: 57 — 26 nonsense_mediated_decay, 16 protein_coding, 11 retained_intron, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000520810

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 16, TSL 3: 4, TSL 4: 3, TSL 5: 3

ENST00000520810, ENST00000342222, ENST00000416505, ENST00000517388, ENST00000517502, ENST00000517812, ENST00000517890, ENST00000517917, ENST00000518647, ENST00000518679, ENST00000518983, ENST00000519733, ENST00000519735, ENST00000519938, ENST00000520201, ENST00000520655, 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, ENST00000982789, ENST00000982790, ENST00000982791, ENST00000982792, ENST00000982793, ENST00000982794, ENST00001022136, ENST00001022137, ENST00001022138, ENST00001022139, ENST00001022140, ENST00001022141, ENST00001089280, ENST00001115158, ENST00001128620

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.

Highest expression (Bgee): spleen, granulocyte, lower esophagus mucosa, lobe of thyroid gland, uterine tube.

Genetic regulation across tissues (GTEx eQTL / sQTL)

IKBKB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	8.2e-12	+0.71	8:42256743:C:T
Brain Cerebellum	eqtl	5.6e-07	+0.40	8:42280646:A:G
Spleen	eqtl	2.0e-06	-0.85	8:42246286:C:T
Skin Not Sun Exposed Suprapubic	eqtl	8.4e-06	+0.15	8:42367498:A:C
Artery Aorta	eqtl	1.2e-05	-0.44	8:42301363:A:G
Adipose Subcutaneous	sqtl	2.7e-04	+0.44	8:42324457:G:T
Skin Sun Exposed Lower leg	eqtl	6.9e-04	-0.13	8:42300384:T:C
Muscle Skeletal	eqtl	1.1e-03	+0.28	8:42292844:C:T
Esophagus Mucosa	sqtl	2.1e-03	-0.40	8:42364595:A:C
Thyroid	eqtl	6.2e-03	-0.21	8:42223904:C:T
Esophagus Muscularis	eqtl	1.2e-02	+0.36	8:42253668:A:G
Brain Cerebellar Hemisphere	eqtl	1.3e-02	+0.24	8:42280646:A:G
Breast Mammary Tissue	sqtl	1.7e-02	+0.65	8:42316559:G:A
Muscle Skeletal	sqtl	1.9e-02	-0.34	8:42280646:A:G
Adipose Visceral Omentum	eqtl	1.9e-02	+0.18	8:42296267:C:T
Esophagus Mucosa	eqtl	2.3e-02	-0.12	8:42166736:C:T
Prostate	eqtl	2.4e-02	+0.43	8:42424592:G:A
Brain Caudate basal ganglia	eqtl	2.7e-02	+0.15	8:41910734:G:A
Thyroid	sqtl	3.0e-02	-0.58	8:42360252:C:T
Testis	sqtl	3.1e-02	+0.52	8:42355738:G:A

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 295 tissues 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
body of pancreas	UBERON:0001150	93.97	gold quality
vermiform appendix	UBERON:0001154	93.93	gold quality
endocervix	UBERON:0000458	93.82	gold quality
saliva-secreting gland	UBERON:0001044	93.76	gold quality
monocyte	CL:0000576	93.75	gold quality
mononuclear cell	CL:0000842	93.74	gold quality
small intestine	UBERON:0002108	93.70	gold quality
leukocyte	CL:0000738	93.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.66	gold quality
right adrenal gland cortex	UBERON:0035827	93.46	gold quality
gall bladder	UBERON:0002110	93.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.45	gold quality
stomach	UBERON:0000945	93.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.42	gold quality
right ovary	UBERON:0002118	93.41	gold quality
left adrenal gland cortex	UBERON:0035825	93.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.41	gold quality
lower esophagus	UBERON:0013473	93.40	gold quality
caecum	UBERON:0001153	93.39	gold quality
transverse colon	UBERON:0001157	93.38	gold quality
right adrenal gland	UBERON:0001233	93.38	gold quality
right lung	UBERON:0002167	93.37	gold quality
epithelium of nasopharynx	UBERON:0001951	93.32	gold quality
left adrenal gland	UBERON:0001234	93.27	gold quality
peritoneum	UBERON:0002358	93.26	gold quality
omental fat pad	UBERON:0010414	93.26	gold quality
cerebellar hemisphere	UBERON:0002245	93.20	gold quality
upper arm skin	UBERON:0004263	93.18	gold quality
prostate gland	UBERON:0002367	93.17	gold quality
sural nerve	UBERON:0015488	93.17	gold quality
adrenal cortex	UBERON:0001235	93.16	gold quality
visceral pleura	UBERON:0002401	93.16	gold quality
descending thoracic aorta	UBERON:0002345	93.10	gold quality
left ovary	UBERON:0002119	93.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.99	gold quality
cerebellar cortex	UBERON:0002129	92.97	gold quality
ascending aorta	UBERON:0001496	92.79	gold quality
thoracic aorta	UBERON:0001515	92.79	gold quality
urinary bladder	UBERON:0001255	92.72	gold quality
parietal pleura	UBERON:0002400	92.68	gold quality
mucosa of transverse colon	UBERON:0004991	92.62	gold quality
adrenal gland	UBERON:0002369	92.55	gold quality
colonic epithelium	UBERON:0000397	92.49	gold quality
pylorus	UBERON:0001166	92.44	gold quality
bone marrow cell	CL:0002092	92.43	gold quality
left coronary artery	UBERON:0001626	92.27	gold quality
muscle of leg	UBERON:0001383	92.26	gold quality
gastrocnemius	UBERON:0001388	92.23	gold quality
adenohypophysis	UBERON:0002196	92.19	gold quality
adipose tissue	UBERON:0001013	92.13	gold quality
pleura	UBERON:0000977	92.03	gold quality
cerebellum	UBERON:0002037	92.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.97	gold quality
connective tissue	UBERON:0002384	91.95	gold quality
cardia of stomach	UBERON:0001162	91.89	gold quality
coronary artery	UBERON:0001621	91.87	gold quality
right coronary artery	UBERON:0001625	91.83	gold quality
intestine	UBERON:0000160	91.82	gold quality
pituitary gland	UBERON:0000007	91.81	gold quality
uterine cervix	UBERON:0000002	91.80	gold quality
aorta	UBERON:0000947	91.61	gold quality
apex of heart	UBERON:0002098	91.61	gold quality
rectum	UBERON:0001052	91.60	gold quality
trabecular bone tissue	UBERON:0002483	91.60	gold quality
colon	UBERON:0001155	91.57	gold quality
myometrium	UBERON:0001296	91.56	gold quality
lung	UBERON:0002048	91.51	gold quality
sigmoid colon	UBERON:0001159	91.48	gold quality
right lobe of liver	UBERON:0001114	91.44	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	22.6
Frontal cortex	tissue	15.0
Spinal cord	tissue	15.0
Corpus callosum	tissue	15.0
Medulla oblongata	tissue	14.2
Substantia nigra	tissue	13.5
Midbrain	tissue	13.2
Superior colliculi	tissue	13.1
Skeletal muscle	tissue	12.9	low
Caudate putamen	tissue	12.8
Parathyroid gland	tissue	12.7	medium
Thalamus	tissue	12.7
Hypothalamus	tissue	12.1
Putamen	tissue	12.0
Pons	tissue	11.9
Smooth muscle	tissue	11.9	low
Choroid plexus	tissue	11.9
Lymph node	tissue	11.5	medium
Retina	tissue	11.4
Periaqueductal gray	tissue	11.2
Septum	tissue	11.0
Tonsil	tissue	10.9	medium
Fallopian tube	tissue	10.9	medium
Skin 1	tissue	10.8	medium
Ventral forebrain	tissue	10.8
Lung	tissue	10.6	medium
Vagina	tissue	10.5	medium
Urinary bladder	tissue	10.4	medium
Hippocampal formation	tissue	10.4
Basal ganglia	tissue	10.2	low
Cerebral cortex	tissue	10.1	medium
Thymus	tissue	10.1
Somatosensory cortex	tissue	10.1
Motor cortex	tissue	9.9
Spleen	tissue	9.9	medium
Esophagus	tissue	9.6	low
Olfactory bulb	tissue	9.4
Amygdala	tissue	9.3
Entorhinal cortex	tissue	9.3
Temporal cortex	tissue	9.3
Prefrontal cortex	tissue	8.9
Retrosplenial cortex	tissue	8.9
Occipital cortex	tissue	8.9
Adipose tissue	tissue	8.8	low
Thyroid gland	tissue	8.8	low
Retrosplenial and cingulate cortex	tissue	8.8
Seminal vesicle	tissue	8.7	low
Insular cortex	tissue	8.7
Salivary gland	tissue	8.4	low
Gallbladder	tissue	8.1	medium
Breast	tissue	7.7	medium
Placenta	tissue	7.7	medium
Adrenal gland	tissue	7.7	low
Endometrium 1	tissue	7.6	medium
Prostate	tissue	7.4	low
Cerebellum	tissue	7.2	low
Pituitary gland	tissue	7.0
Epididymis	tissue	7.0	medium
Cervix	tissue	6.8	medium
Ovary	tissue	6.5	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal spinal cord (15.0), White matter (15.0), Ventral spinal cord (14.4), Blood vessel (10.4), Dorsal hippocampus (10.4).

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)

Targeting IKBKB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 79 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.996, LOEUF 0.472, missense Z 3.32 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000520810 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:42,272,101–42,314,346	167 / 301.0	0.55	no
8:42,314,347–42,330,976	506 / 638.7	0.79	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1338071) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 75 distinct phenotype terms.

Mouse phenotype (MP)	Records
liver degeneration	3
increased fibroblast apoptosis	3
abnormal hepatocyte morphology	2
abnormal B cell physiology	2
increased hepatocyte apoptosis	2
decreased B-1 B cell number	2
increased B cell number	2
decreased B cell number	2
decreased T cell number	2
abnormal cell physiology	2
decreased CD4-positive, alpha-beta T cell number	2
decreased CD8-positive, alpha-beta T cell number	2
decreased marginal zone B cell number	2
decreased interleukin-6 secretion	2
impaired neutrophil recruitment	2
embryonic lethality during organogenesis, complete penetrance	2
increased cell proliferation	1
abnormal intestinal mucosa morphology	1
small liver	1
dissociated hepatocytes	1
abnormal spleen morphology	1
enlarged spleen	1
psoriasis	1
increased body weight	1
decreased body weight	1

+50 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q95KV1	97.0%	Diamond
Xenopus laevis	Q6GM53	95.7%	Diamond
Xenopus tropicalis	Q28DZ1	95.6%	Diamond
Gallus gallus	Q5ZJB4	81.6%	Diamond
Oryza sativa Japonica Group	Q7XIT1	42.9%	Diamond
Arabidopsis thaliana	Q93VJ2	42.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
IKBKB-DT	ncRNA	101929897
DKK4	protein-coding	27121
POLB	protein-coding	5423
VDAC3	protein-coding	7419
PLAT	protein-coding	5327
AP3M2	protein-coding	10947
SMIM19	protein-coding	114926
SLC20A2	protein-coding	6575

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)

• 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 (102 total): helix 28, 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 by resolution:

PDB	Title	Method	Resolution (Å)
3BRV	NEMO/IKKb association domain structure	X-RAY DIFFRACTION	2.2
3BRT	NEMO/IKK association domain structure	X-RAY DIFFRACTION	2.25
4KIK	Human IkB kinase beta	X-RAY DIFFRACTION	2.83
4E3C	X-ray crystal structure of human IKK2 in an active conformation	X-RAY DIFFRACTION	3.98
8OMV	Crystal structure of the constitutively active S117E/S181E mutant of human IKK2	X-RAY DIFFRACTION	4.16

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH enhanced · IF supported

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)

Position	Role
145	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
21–29	ATP
44	ATP

Post-translational modifications (19)

Type	Positions
S-nitrosocysteine	179
(microbial infection) o-acetylthreonine	180
Phosphoserine	181, 670, 672, 675, 675, 682, 689, 692, 695, 697, 705, 733, 740, 750, 177
Hydroxyproline	191
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	163

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 with r-163 and e-181 …
181	decrease of activity.
181	full activation. interaction with trim21 is enhanced; when associated with e-177. monoubiquitinated; when associated with r-163 and e-177 …
191	loss of hypoxic inducibility.
272–756	loss of activation of nf-kappa-b signaling.

Function

Pathways and Gene Ontology

Reactome pathways

28 curated (TAS) of 82; 12 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 82 pathways:

ID	Pathway	Evidence
R-HSA-5602636	IKBKB deficiency causes SCID ⚕	curated
R-HSA-5603027	IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) ⚕	curated
R-HSA-5603029	IkBA variant leads to EDA-ID ⚕	curated
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses ⚕	curated
R-HSA-5607764	CLEC7A (Dectin-1) signaling	curated
R-HSA-202424	Downstream TCR signaling	curated
R-HSA-1236974	ER-Phagosome pathway	curated
R-HSA-2871837	FCERI mediated NF-kB activation	curated
R-HSA-937041	IKK complex recruitment mediated by RIP1	curated
R-HSA-937039	IRAK1 recruits IKK complex	curated
R-HSA-975144	IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation	curated
R-HSA-9020702	Interleukin-1 signaling	curated
R-HSA-5684264	MAP3K8 (TPL2)-dependent MAPK1/3 activation	curated
R-HSA-9909505	Modulation of host responses by IFN-stimulated genes	curated
R-HSA-933543	NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	curated
R-HSA-209560	NF-kB is activated and signals survival	curated
R-HSA-168638	NOD1/2 Signaling Pathway	curated
R-HSA-9833482	PKR-mediated signaling	curated
R-HSA-1810476	RIP-mediated NFkB activation via ZBP1	curated
R-HSA-9758274	Regulation of NF-kappa B signaling	curated
R-HSA-5357905	Regulation of TNFR1 signaling	curated
R-HSA-9860276	SLC15A4:TASL-dependent IRF5 activation	curated
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation	curated
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment	curated
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway	curated
R-HSA-933542	TRAF6 mediated NF-kB activation	curated
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	curated
R-HSA-209543	p75NTR recruits signalling complexes	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5602358	Diseases associated with the TLR signaling cascade ⚕	—
R-HSA-5260271	Diseases of Immune System ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9694516	SARS-CoV-2 Infection ⚕	—
R-HSA-9705683	SARS-CoV-2-host interactions ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-1169091	Activation of NF-kappaB in B cells	electronic
R-HSA-1280218	Adaptive Immune System	—
R-HSA-1236975	Antigen processing-Cross presentation	—
R-HSA-1169410	Antimicrobial mechanism of IFN-stimulated genes	—
R-HSA-5621481	C-type lectin receptors (CLRs)	—
R-HSA-9855142	Cellular responses to mechanical stimuli	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-983169	Class I MHC mediated antigen processing & presentation	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1834949	Cytosolic sensors of pathogen-associated DNA	—
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta	—
R-HSA-73887	Death Receptor Signaling	—
R-HSA-1168372	Downstream signaling events of B Cell Receptor (BCR)	—
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-913531	Interferon Signaling	—
R-HSA-446652	Interleukin-1 family signaling	—
R-HSA-448424	Interleukin-17 signaling	—
R-HSA-450294	MAP kinase activation	—
R-HSA-975871	MyD88 cascade initiated on plasma membrane	—
R-HSA-975155	MyD88 dependent cascade initiated on endosome	—
R-HSA-166166	MyD88-independent TLR4 cascade	—
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane	—

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 (29): 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), inflammatory response (GO:0006954), canonical NF-kappaB signal transduction (GO:0007249), response to virus (GO:0009615), 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), 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), pattern recognition receptor signaling pathway (GO:0002221), positive regulation of macromolecule metabolic process (GO:0010604)

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 (7): 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)

Reactome top-level categories

19 top-level categories:

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
MyD88 cascade initiated on plasma membrane	1
C-type lectin receptors (CLRs)	1
MAP kinase activation	1
Interleukin-1 family signaling	1

GO top-level categories

showing 60 of 61 GO namespaces:

Category	Terms
toll-like receptor signaling pathway	2
protein kinase activity	2
protein binding	2
protein dimerization activity	2
cellular anatomical structure	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
defense response	1
intracellular signaling cassette	1
response to other organism	1
regulation of cytokine-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
protein phosphorylation	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
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
antigen receptor-mediated signaling pathway	1
MAPK cascade	1
stress-activated protein kinase signaling cascade	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein serine/threonine kinase activity	1
I-kappaB phosphorylation	1
kinase binding	1
identical protein binding	1
signaling receptor binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytosol	1
serine/threonine protein kinase complex	1
plasma membrane	1
cytoplasmic side of membrane	1
plasma membrane signaling receptor complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 51 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
canonical NF-kappaB signal transduction	BP	direct assay
cellular response to tumor necrosis factor	BP	direct assay
interleukin-1-mediated signaling pathway	BP	mutant phenotype
negative regulation of bicellular tight junction assembly	BP	mutant phenotype
negative regulation of cytokine production involved in inflammatory response	BP	direct assay
peptidyl-serine phosphorylation	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of canonical NF-kappaB signal transduction	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
protein localization to plasma membrane	BP	mutant phenotype
protein maturation	BP	direct assay
protein phosphorylation	BP	direct assay
regulation of establishment of endothelial barrier	BP	mutant phenotype
tumor necrosis factor-mediated signaling pathway	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
IkappaB kinase activity	MF	direct assay
identical protein binding	MF	physical interaction
protein heterodimerization activity	MF	direct assay
protein homodimerization activity	MF	direct assay
protein kinase activity	MF	direct assay
protein kinase binding	MF	physical interaction
protein serine/threonine kinase activity	MF	direct assay
scaffold protein binding	MF	direct assay
transferrin receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,210 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IKBKB	IKBKG	Q9Y6K9	951
IKBKB	NFKBIA	P25963	945
IKBKB	NFKB1	P19838	902
IKBKB	CHUK	O15111	890
IKBKB	RELA	Q04206	886
IKBKB	TNF	P01375	869
IKBKB	IL1B	P01584	866
IKBKB	TRAF6	Q9Y4K3	865
IKBKB	RELB	Q01201	860
IKBKB	NFKB2	Q00653	850
IKBKB	NFKBIB	Q15653	847
IKBKB	REL	Q04864	845
IKBKB	MYD88	P78397	832
IKBKB	TAB2	Q9NYJ8	813
IKBKB	TLR4	O00206	799

IntAct

Human interaction partners of IKBKB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 93 partners by confidence:

Partner	Interaction type	MIscore	Records
IKBKG	association	0.980	37
NFKBIA	phosphorylation reaction	0.970	25
CHUK	association	0.960	21
MAP3K14	phosphorylation reaction	0.900	5
CDC37	association	0.850	2
NFKB1	association	0.770	4
RELA	proximity	0.750	3
TP53	phosphorylation reaction	0.690	3
MAP3K7	colocalization	0.660	6
PPP2CA	association	0.640	3
FKBP5	association	0.640	2
STAP2	association	0.620	6
OPG200	physical association	0.620	3
KEAP1	physical association	0.610	6
TSC1	physical association	0.610	3
BRAF	physical association	0.600	4
RPS3	physical association	0.600	4
N	physical association	0.580	6
MAVS	physical association	0.560	1
HSP90AB1	proximity	0.540	3
AURKA	physical association	0.540	2
CLTC	proximity	0.540	2
NLRC5	physical association	0.520	2
PYCARD	association	0.510	3
IKBIP	physical association	0.500	3
LMP1	physical association	0.500	2
TNIK	physical association	0.500	2
CREBBP	proximity	0.480	2
TRAF2	proximity	0.480	1
MAP3K1	phosphorylation reaction	0.440	1

BioGRID (711 interactions; top human partners by supporting records in a sample of 600 records): IKBKG (Affinity Capture-Western; 82 records), NFKBIA (Biochemical Activity; 40 records), CHUK (Affinity Capture-MS; 31 records), MAP3K7 (Affinity Capture-Western; 15 records), KEAP1 (Affinity Capture-Western; 11 records), TNFRSF1A (Co-localization; 11 records), CDC37 (Affinity Capture-MS; 8 records), NFKB1 (Co-localization; 8 records), RELA (Biochemical Activity; 8 records), TRAF2 (Co-localization; 8 records), COPS5 (Affinity Capture-Western; 7 records), NCOA3 (Affinity Capture-MS; 7 records), MAP3K14 (Affinity Capture-MS; 6 records), BTRC (Affinity Capture-Western; 5 records), GLI1 (Affinity Capture-MS; 5 records)

SIGNOR signaling

showing 29 of 154 signaling 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
PPM1B	down-regulates	IKBKB	dephosphorylation
PLK1	down-regulates	IKBKB	phosphorylation
IKBKB	down-regulates	BAD	phosphorylation
IKBKB	“down-regulates activity”	CYLD	phosphorylation
IKBKB	“up-regulates activity”	CYLD	phosphorylation
IKBKB	unknown	NfKb-p65/p50	phosphorylation
IKBKB	down-regulates	NfKb-p65/p50	phosphorylation
IKBKB	“down-regulates activity”	IKBKB	phosphorylation
PPM1B	“down-regulates activity”	IKBKB	dephosphorylation
PPM1A	“down-regulates activity”	IKBKB	dephosphorylation
PPP2CB	“down-regulates activity”	IKBKB	dephosphorylation
PRKCZ	“up-regulates activity”	IKBKB	phosphorylation

Protein complexes (CORUM) (17)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

17 complexes by size:

Complex	Subunits	Members
★ TNFalpha-NFkappa B signaling complex 5	25	IQGAP2, MTIF2, POLR1A, POLR1E, RASAL2, RELA, SKP1, CHUK, KPNA2, NFKB2, NFKBIB, POLR2H, REL, IKBKB, MCC, POLR1D, CUL1, FBXW11, LRPPRC, NFKB1, PDCD2, POLR1B, POLR1G, POLR2L, IKBKG
★ TNFR1 signaling complex, TNF-induced	24	TNIP1, TRAF2, BIRC2, BIRC3, IKBKB, MAP3K7, SHARPIN, TAB2, TBK1, TNIP2, RNF31, TNFAIP3, CYLD, HTRA2, IKBKE, RBCK1, RIPK1, TANK, TNFRSF1A, TRADD, CHUK, IKBKG, SPATA2, TNF
★ TNFR1 signaling complex, native	15	CHUK, RIPK1, TNF, TRADD, TNIP1, BIRC3, MAP3K7, RBCK1, RNF31, TAB2, TNFRSF1A, TRAF2, IKBKB, IKBKG, TAB1
★ TNF-alpha/NF-kappa B signaling complex 6	14	MAP3K14, RPL30, RPL4, RPL6, RPL8, RPS11, CDC37, CHUK, FBL, HSP90AA1, HSP90AB1, IKBKB, IKBKG, RPS13
TNF-alpha/NF-kappa B signaling complex (SEC16A, CHUK, IKBKB, NFKB2, REL, IKBKG, MAP3K14, RELA, FBXW7, USP2)	10	REL, SEC16A, IKBKB, MAP3K14, NFKB2, RELA, USP2, CHUK, FBXW7, IKBKG
SRC-3 complex	7	CHUK, CREBBP, IKBKB, IKBKG, NCOA2, NCOA3, RO60
IkappaB kinase complex (IKBKB, CHUK, IKBKAP, NFKBIA, RELA, MAP3K14)	6	RELA, CHUK, ELP1, IKBKB, MAP3K14, NFKBIA
CASP8-CHUK-IKBKB-MALT1-BCL10 complex	5	IKBKB, MALT1, BCL10, CASP8, CHUK
★ CDC37-HSP90AA1-HSP90AB1-IKBKB-KIAA1967 complex	5	IKBKB, CCAR2, CDC37, HSP90AA1, HSP90AB1
CHUK-ERC1-IKBKB-IKBKG complex	4	ERC1, IKBKB, IKBKG, CHUK
★ CHUK-HSP90-IKBKB-TOMM70 complex	4	IKBKB, TOMM70, CHUK, HSP90AA1
★ BCL10-CARD11-DPP4-IKBKB complex	4	BCL10, CARD11, DPP4, IKBKB
CHUK-IKBKB-MAP3K14 complex	3	CHUK, IKBKB, MAP3K14
I-kappa-B kinase complex	3	IKBKB, IKBKG, CHUK
CHUK-IKBKB complex	2	CHUK, IKBKB
IKBKB-MAP3K14 complex	2	IKBKB, MAP3K14
IKBKG-IKBKB complex	2	IKBKB, IKBKG

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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	64.0×	5e-11
TRAF6 mediated NF-kB activation	10	54.4×	8e-13
Regulation of NF-kappa B signaling	7	52.9×	2e-09
TNF signaling	8	40.3×	1e-09
The NLRP3 inflammasome	5	40.0×	3e-06
TNFR1-induced proapoptotic signaling	7	36.6×	2e-08
TNFR1-induced NF-kappa-B signaling pathway	9	36.0×	2e-10
RHO GTPases activate IQGAPs	8	33.0×	5e-09

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	9	87.2×	1e-13
canonical NF-kappaB signal transduction	14	59.0×	1e-18
tumor necrosis factor-mediated signaling pathway	11	41.8×	6e-13
regulation of tumor necrosis factor-mediated signaling pathway	5	40.4×	2e-05
protein refolding	5	35.9×	3e-05
lipopolysaccharide-mediated signaling pathway	5	30.3×	5e-05
toll-like receptor 4 signaling pathway	5	30.3×	5e-05
negative regulation of cytokine production involved in inflammatory response	5	24.2×	1e-04

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for IKBKB: 886 ClinVar records (37 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	18
Uncertain significance	290
Likely benign	461
Benign	32

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 37 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
957808	NM_001556.3(IKBKB):c.856C>T (p.Arg286Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
590941	NM_001556.3(IKBKB):c.607G>A (p.Val203Ile)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
157663	NM_001556.3(IKBKB):c.814C>T (p.Arg272Ter)	Pathogenic	criteria provided, single submitter	2
1357742	NM_001556.3(IKBKB):c.163C>T (p.Arg55Ter)	Pathogenic	criteria provided, single submitter	1
1388684	NM_001556.3(IKBKB):c.1927_1928del (p.Val643fs)	Pathogenic	criteria provided, single submitter	1
1433844	NM_001556.3(IKBKB):c.1705G>T (p.Glu569Ter)	Pathogenic	criteria provided, single submitter	1
1451255	NM_001556.3(IKBKB):c.1731dup (p.Pro578fs)	Pathogenic	criteria provided, single submitter	1
1453689	NM_001556.3(IKBKB):c.25del (p.Thr9fs)	Pathogenic	criteria provided, single submitter	1
2080261	NM_001556.3(IKBKB):c.1609del (p.Arg536_Met537insTer)	Pathogenic	criteria provided, single submitter	1
2096950	NM_001556.3(IKBKB):c.1762C>T (p.Gln588Ter)	Pathogenic	criteria provided, single submitter	1
2131114	NM_001556.3(IKBKB):c.1392C>A (p.Cys464Ter)	Pathogenic	criteria provided, single submitter	1
2696833	NM_001556.3(IKBKB):c.1696C>T (p.Gln566Ter)	Pathogenic	criteria provided, single submitter	1
2768865	NM_001556.3(IKBKB):c.2116del (p.Glu706fs)	Pathogenic	criteria provided, single submitter	1
2844327	NM_001556.3(IKBKB):c.1847_1848del (p.Val616fs)	Pathogenic	criteria provided, single submitter	1
2856021	NM_001556.3(IKBKB):c.1429C>T (p.Gln477Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore IKBKB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 2,150):

Position(s)	Effect	Δscore	Sites
8:42290154–42290155	acceptor_loss	1.0000	6
8:42290274–42290275	donor_loss	1.0000	5
8:42305276–42305277	donor_loss	1.0000	4
8:42309026–42309027	donor_loss	1.0000	5
8:42314320–42314321	acceptor_loss	1.0000	4
8:42316207	acceptor_gain	1.0000
8:42316208–42316209	acceptor_loss	1.0000	6
8:42316340	donor_loss	1.0000
8:42316709	acceptor_loss	1.0000
8:42316905–42316906	donor_loss	1.0000	5

AlphaMissense

2,023 missense substitutions predicted likely pathogenic (of 4,983 scored), across 487 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M96	9	0.963	0.999
M65	9	0.936	0.999
M517	9	0.883	0.985
D145	8	1.000	1.000
N150	8	1.000	1.000
D166	8	1.000	1.000
D204	8	1.000	1.000
H143	8	0.999	1.000
F26	8	0.997	1.000
H137	8	0.997	0.999
D493	8	0.997	0.998
F182	8	0.996	1.000
F222	8	0.993	1.000
D103	8	0.987	0.998
S207	8	0.982	1.000
D128	8	0.975	0.998
H70	8	0.971	0.998
D174	8	0.959	0.988
S177	8	0.955	0.999
F486	8	0.950	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.6e-05

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
immunodeficiency 15a	Strong	Autosomal recessive	5
severe combined immunodeficiency due to IKK2 deficiency	Strong	Autosomal recessive	4

ClinGen Gene-Disease Validity

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

2 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (3): severe combined immunodeficiency due to IKK2 deficiency (MONDO:0014267), immunodeficiency 15a (MONDO:0032599), severe combined immunodeficiency (MONDO:0015974)

Orphanet (3): Combined immunodeficiency due to IKBKB deficiency (Orphanet:397787), Combined immunodeficiency due to IKBKB gain-of-function mutation (Orphanet:700205), Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

24 phenotypes (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	Recurrent mucocutaneous candidiasis
HP:0003593	Infantile onset
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0004432	Agammaglobulinemia
HP:0005415	Decreased total CD8+ T cell proportion
HP:0009098	Recurrent oral thrush
HP:0011108	Recurrent sinusitis
HP:0011463	Childhood onset
HP:0012311	Increased total monocyte count
HP:0030374	Decreased memory B cell proportion
HP:0031292	Cutaneous abscess
HP:0031381	Decreased mitogen-induced T-cell proliferation
HP:0032218	Decreased total CD4+ T cell proportion
HP:0040154	Acne inversa
HP:0040218	Reduced total natural killer cell count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the IKBKB protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

7 curated-mechanism drugs:

Drug	Modality	Max phase
BARDOXOLONE METHYL	Small molecule	3
IMD-1041	Unknown	2
SAR-113945	Unknown	2
AS-602868	Small molecule	1
IMD-0354	Small molecule	1
IMD-2560	Unknown	1
MLN-0415	Small molecule	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 352,624 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

16 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL384467	DEXAMETHASONE	4	282,026
CHEMBL231884	DIOSMIN	4	4,951
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL603469	LESTAURTINIB	3
CHEMBL6246	ELLAGIC ACID	2	23,439
CHEMBL184041	ERTIPROTAFIB	2	179
CHEMBL475251	R-406	2	787
CHEMBL1721885	SU-014813	2	375
CHEMBL363648	TAK-715	2	458
CHEMBL129857	AS-602868	1	99
CHEMBL536151	IMD-0354	1	482
CHEMBL574738	AST-487	1	468
CHEMBL1908397	KW-2449	1	655

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	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

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2272733	IKBKB	3	2.50	1	gefitinib
rs9694958	IKBKB	3	2.00	1	gefitinib

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2272733	gefitinib	Toxicity	Genotype CC is associated with decreased risk of Exanthema due to gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes CT + TT.	PMID:31664190
rs9694958	gefitinib	Toxicity	Genotype AA is associated with increased risk of Exanthema due to gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AG + GG.	PMID:31664190

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)

1284 measured of 1572 human assays (1580 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
(1R)-N-(4-propylisoquinolin-6-yl)-2-[4-(pyrimidin-2-ylsulfamoyl)phenyl]cyclopropane-1-carboxamide	IC50	0.1 nM	US-11427563: Aryl cyclopropyl-amino-isoquinolinyl amide compounds
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

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 3873 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	increases expression, increases reaction, decreases reaction, increases phosphorylation, increases activity	7
sodium arsenite	affects response to substance, affects expression, decreases expression, increases activity, increases expression	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	increases ubiquitination, decreases reaction, decreases expression, increases expression, increases activity (+2 more)	4
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases activity, increases phosphorylation, decreases activity, decreases expression, decreases reaction	3
Bortezomib	increases degradation, increases phosphorylation, decreases expression, increases reaction, affects reaction	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	affects cotreatment, increases expression, increases phosphorylation, decreases reaction	3
Tetradecanoylphorbol Acetate	decreases reaction, increases activity, increases phosphorylation, increases reaction, increases expression	3
Particulate Matter	affects cotreatment, increases abundance, increases expression	3
arsenite	increases reaction, decreases activity, decreases expression, increases expression, affects binding (+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 phosphorylation, decreases activity, increases reaction	2
Vorinostat	affects cotreatment, decreases expression, decreases phosphorylation	2
Acetylcysteine	decreases reaction, increases abundance, increases phosphorylation, decreases activity	2
Acrolein	increases abundance, affects metabolic processing, affects cotreatment, decreases expression, increases oxidation	2
Vehicle Emissions	increases expression, increases abundance, affects cotreatment	2
Cisplatin	increases expression, affects response to substance	2
Copper	affects binding, increases expression, decreases activity, decreases response to substance	2
Doxorubicin	increases reaction, increases phosphorylation, decreases reaction, increases degradation	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance, increases degradation (+1 more)	2
Plant Extracts	affects cotreatment, increases expression, decreases reaction	2
Quercetin	decreases reaction, increases phosphorylation	2
Zinc	affects expression, affects binding, increases localization, increases expression	2
Simvastatin	decreases reaction, increases phosphorylation, increases reaction, decreases expression	2
Apigenin	decreases reaction, increases phosphorylation, increases expression, increases activity, decreases 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 99 trials:

NCT	Phase	Status	Title
NCT02343562	Phase 4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	Phase 4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT00220766	Phase 3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	Phase 3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	Phase 3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT03660176	Phase 3	NOT_YET_RECRUITING	Effects of Butyrate Enemas on Postoperative Intestinal Motility Disorders in Hirschsprung’s Disease
NCT04904081	Phase 3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00000603	Phase 2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	Phase 2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	Phase 2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	Phase 2	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	Phase 2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	Phase 2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	Phase 2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
NCT00630838	Phase 2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00008450	Phase 1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	Phase 1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	Phase 1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	Phase 1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01019876	Phase 2/3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00228852	Phase 1/2	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	Phase 1/2	TERMINATED	Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
NCT01129544	Phase 1/2	COMPLETED	Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
NCT01852370	Phase 1/2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02127892	Phase 1/2	TERMINATED	SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02963064	Phase 1/2	TERMINATED	JSP191 Antibody Targeting Conditioning in SCID Patients
NCT03513328	Phase 1/2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03538899	Phase 1/2	RECRUITING	Autologous Gene Therapy for Artemis-Deficient SCID
NCT03597594	Phase 1/2	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
NCT02590328	Not specified	COMPLETED	Neonatal Screening of Severe Combined Immunodeficiencies
NCT04049084	Not specified	ENROLLING_BY_INVITATION	An Observational LTFU Study for Patients Previously Treated With Autologous ex Vivo Gene Therapy for ADA-SCID
NCT04172181	Not specified	UNKNOWN	Multi-center Clinical Study of Cord Blood Stem Cell Transplantation for SCID
NCT04246840	Not specified	COMPLETED	Study Through Imaging of Visceral Lymphoid Organs in Patients With SCID Who Have Recieved Bone Marrow Allograft
NCT04331483	Not specified	WITHDRAWN	A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts
NCT05298930	Not specified	COMPLETED	Feasibility Study to Assess an Adapted Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Transplantation
NCT05651113	Not specified	RECRUITING	The Experience of Screening for SCID
NCT06659588	Not specified	RECRUITING	Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency
NCT06731036	Not specified	AVAILABLE	Expanded Access to CD34+ Selection Utilizing Miltenyi CliniMACS Prodigy® for Patients Receiving Peripheral Blood Stem Cell Transplantations and Stem Cell Boosts
NCT00671684	Phase 1/2	UNKNOWN	Endoscopic Mucosal Resection (EMR) for Diagnosis of Hirschsprung’s Disease
NCT01985646	Early Phase 1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for IKBKB across ~30M SureChEMBL compounds — explore on Sugi Predict.