IKBKB

Chr 8p11.21

inhibitor of nuclear factor kappa B kinase subunit beta

Aliases:: IKK2, NFKBIKB, IKK-beta, IKKB
MANE:: ENST00000520810.6

OMIM: 603258 ↗NCBI: 3551 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

IKBKB · O14920

v62025-08-01

Predicted Aligned Error matrix for IKBKB — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

86.6/ 100

Confident

756 residues

Confidence breakdown

Very high(≥ 90)69%
Confident(70–90)17%
Low(50–70)6%
Very low(< 50)8%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Disease associations (Open Targets)

severe combined immunodeficiency due to IKK2 deficiency
0.78
immunodeficiency 15a
0.65
severe combined immunodeficiency
0.59
COVID-19
0.48
combined immunodeficiency
0.47
plasma cell myeloma
0.44
lung carcinoma
0.39
systemic lupus erythematosus
0.38
skin basal cell carcinoma
0.37
colorectal adenocarcinoma
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Inhibitor of nuclear factor kappa-B kinase subunit beta

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 (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). 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 (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). 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 (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). 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 (PubMed:38621137). 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 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697)