IKBKE

inhibitor of nuclear factor kappa B kinase subunit epsilon, the group of MicroRNA protein coding host genes|I kappa B kinases

Basic information

Region (hg38): 1:206470475-206496889

Links

ENSG00000263528 ∙ NCBI:9641 ∙ OMIM:605048 ∙ HGNC:14552 ∙ Uniprot:Q14164 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IKBKE gene.

• Inborn genetic diseases (24 variants)
• not provided (8 variants)
• Autoimmune connective tissue disease and vasculitis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IKBKE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense			23	1		24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			1	1	1	3
Total	0	0	24	2	4

Variants in IKBKE

This is a list of pathogenic ClinVar variants found in the IKBKE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-206473279-G-A		not specified	Uncertain significance (Jun 24, 2022)
1-206473323-C-A			Benign (Jul 13, 2018)
1-206474379-C-T			Likely benign (Sep 01, 2022)
1-206474380-T-C		not specified	Uncertain significance (Jan 23, 2024)
1-206474382-C-T		not specified	Uncertain significance (Dec 20, 2023)
1-206474389-G-A		not specified	Uncertain significance (May 24, 2023)
1-206474422-G-A		not specified	Uncertain significance (Sep 29, 2023)
1-206474445-G-A		not specified	Likely benign (Dec 07, 2023)
1-206474470-C-T		not specified	Uncertain significance (Mar 17, 2023)
1-206476204-G-A		not specified	Uncertain significance (Mar 02, 2023)
1-206476264-G-C		not specified	Uncertain significance (Jan 29, 2024)
1-206476326-G-T		not specified	Uncertain significance (Mar 04, 2024)
1-206476338-G-A			Benign (Mar 29, 2018)
1-206476673-G-A		Autoimmune connective tissue disease and vasculitis	Uncertain significance (Dec 17, 2022)
1-206476711-A-G		not specified	Uncertain significance (Jul 17, 2023)
1-206476714-C-T		not specified	Uncertain significance (Jun 16, 2023)
1-206476727-C-T		not specified	Uncertain significance (Mar 31, 2022)
1-206476732-G-A		not specified	Uncertain significance (May 04, 2022)
1-206476843-G-A			Likely benign (Jul 06, 2018)
1-206477792-G-A			Likely benign (Sep 01, 2022)
1-206477810-G-A		not specified	Uncertain significance (Oct 25, 2022)
1-206477834-C-T		not specified	Uncertain significance (Feb 28, 2024)
1-206478250-G-C		not specified	Uncertain significance (Feb 06, 2024)
1-206478253-C-T			Benign (Jul 13, 2018)
1-206478997-C-A		not specified	Uncertain significance (Jun 29, 2023)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG- I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1. {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265}.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Influenza A - Homo sapiens (human);Cytosolic DNA-sensing pathway - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;Cardiac Hypertrophic Response;Toll-like Receptor Signaling;RIG-I-like Receptor Signaling;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Toll-like Receptor Signaling Pathway;TICAM1-dependent activation of IRF3/IRF7;Toll Like Receptor 3 (TLR3) Cascade;Toll-Like Receptors Cascades;TRAF6 mediated IRF7 activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Innate Immune System;Immune System;TRAF3-dependent IRF activation pathway;IL-7 signaling;Negative regulators of DDX58/IFIH1 signaling;JAK STAT pathway and regulation;EPO signaling;TNFalpha;Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;VEGF (Consensus)

Recessive Scores

• pRec: 0.191

Intolerance Scores

• loftool: 0.680
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.28

Haploinsufficiency Scores

• pHI: 0.449
• hipred: Y
• hipred_score: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.915

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ikbke
• Phenotype: respiratory system phenotype; normal phenotype; immune system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: protein phosphorylation;immune response;I-kappaB phosphorylation;intrinsic apoptotic signaling pathway in response to DNA damage;positive regulation of lipid storage;viral process;peptidyl-serine phosphorylation;negative regulation of type I interferon production;response to type I interferon;response to interferon-beta;TRIF-dependent toll-like receptor signaling pathway;NIK/NF-kappaB signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;protein homooligomerization;cellular response to virus
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;endosome membrane;PML body;mitochondrial membrane
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;NF-kappaB-inducing kinase activity;protein binding;ATP binding;IkappaB kinase activity;protein phosphatase binding;ubiquitin protein ligase binding;K48-linked polyubiquitin modification-dependent protein binding;K63-linked polyubiquitin modification-dependent protein binding