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This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
IRAK4 (Interleukin 1 Receptor Associated Kinase 4) is a Protein Coding gene. Diseases associated with IRAK4 include Irak4 Deficiency and Invasive Pneumococcal Disease, Recurrent Isolated. Among its related pathways are Bacterial infections in CF airways and NF-KappaB Family Pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is IRAK1.
The IRAKs (Interleukin-1 receptor-associated kinases) are serine-threonine kinases, EC 2.7.11.1, that are essential regulators of IL-1R and TLR-mediated signaling. Four IRAK isoforms have been identified to date, IRAK1, IRAK2, IRAK3 (IRAK-M) and IRAK4.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0000287 | magnesium ion binding | IEA | -- |
GO:0004672 | protein kinase activity | EXP | 11960013 |
GO:0004674 | protein serine/threonine kinase activity | TAS | -- |
GO:0005149 | interleukin-1 receptor binding | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005615 | extracellular space | IEA | -- |
GO:0005634 | nucleus | IBA | 21873635 |
GO:0005737 | cytoplasm | IBA | 21873635 |
GO:0005829 | cytosol | TAS | -- |
GO:0005886 | plasma membrane | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Activated TLR4 signalling | ||
2 | Diseases associated with the TLR signaling cascade | ||
3 | Toll-like Receptor Signaling Pathway |
.37
|
|
4 | Toll Comparative Pathway |
TLR-TRIF Pathway
.61
Toll Comparative Pathway
.61
Immune response MIF in innate immunity response
.46
|
IL-1 Pathway
.39
iNOS Signaling
.34
|
5 | Toll-Like receptor Signaling Pathways |
Mucin expression in CF via TLRs, EGFR signaling pathways
.42
Immune response IL-1 signaling pathway
.41
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001816 | cytokine production | IEA | -- |
GO:0002224 | toll-like receptor signaling pathway | TAS | 21269878 |
GO:0002376 | immune system process | IEA | -- |
GO:0002446 | neutrophil mediated immunity | IMP | 19663824 |
GO:0002755 | MyD88-dependent toll-like receptor signaling pathway | TAS | 21269878 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
fostamatinib | Approved, Investigational | Pharma | Target, inhibitor | Kinase Inhibitors | 0 | |
Magnesium | Approved, Experimental, Investigational | Pharma | 0 | |||
1-(3-HYDROXYPROPYL)-2-[(3-NITROBENZOYL)AMINO]-1H-BENZIMIDAZOL-5-YL PIVALATE | Experimental | Pharma | Target | 0 | ||
ATP | Investigational | Nutra | Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation | 0 | ||
IRAK inhibitor 1 | Pharma | IRAK-4 inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
Compound | Action | Cas Number |
---|---|---|
IRAK inhibitor 1 | IRAK-4 inhibitor | 1042224-63-4 |
IRAK inhibitor 2 | 928333-30-6 | |
IRAK inhibitor 3 | 1012343-93-9 | |
IRAK inhibitor 4 | IRAK inhibitor | 1012104-68-5 |
IRAK inhibitor 6 | IRAK-4 inhibitor | 1042672-97-8 |
IRAK-1-4 Inhibitor I | IRAK-1/4 inhibitor | 509093-47-4 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | ^ | 2 | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6a | · | 6b | ^ | 7a | · | 7b | · | 7c | ^ | 8a | · | 8b | · | 8c | ^ | 9a | · | 9b | ^ | 10 | ^ | 11a | · | 11b | ^ | 12 | ^ | 13 | ^ | 14 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | |||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP9: |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | IRAK4 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | IRAK4 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | IRAK4 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Irak4 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Mouse (Mus musculus) |
Mammalia | Irak4 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | IRAK4 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | IRAK4 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | IRAK4 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | irak4 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | irak4 30 31 |
|
OneToOne | |
-- 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | pll 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | pik-1 31 32 |
|
OneToMany | |
Thale Cress (Arabidopsis thaliana) |
eudicotyledons | APK2A 30 |
|
||
Rice (Oryza sativa) |
Liliopsida | Os10g0405100 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 12 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
638849 | Uncertain Significance: Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency | 43,768,146(+) | G/A | MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT | |
639567 | Uncertain Significance: Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency | 43,768,224(+) | C/G | MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT | |
643876 | Uncertain Significance: Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency | 43,772,351(+) | T/A | MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT | |
644295 | Uncertain Significance: Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency | 43,786,501(+) | T/G | MISSENSE_VARIANT | |
649132 | Uncertain Significance: Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency | 43,782,428(+) | A/C | MISSENSE_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv285e199 | CNV | deletion | 23128226 |
Disorder | Aliases | PubMed IDs |
---|---|---|
irak4 deficiency |
|
|
invasive pneumococcal disease, recurrent isolated |
|
|
myd88 deficiency |
|
|
maxillary sinusitis |
|
|
meningitis |
|