IRAK4 Gene: Interleukin-1 Receptor Associated Kinase 4
Key mediator in innate immune signaling, associated with recurrent bacterial infections and potential cancer implications.
Gene Information Card
| Symbol | IRAK4 |
|---|---|
| Full Name | Interleukin-1 receptor associated kinase 4 |
| Gene Type | protein coding |
| Chromosomal Location | 12q12 |
| NCBI Gene ID | 51135 ncbi.nlm.nih.gov/gene/51135 |
| Ensembl ID | ENSG00000198001 |
| UniProt ID | Q9NWZ3 |
| OMIM ID | 606883 |
| HGNC ID | 17988 |
| Aliases | IPD1, IRAK-4, NY-REN-64 |
Description
IRAK4 encodes a serine/threonine kinase that plays a critical role in innate immune signaling. It is a key component of the MyD88-dependent pathway downstream of Toll-like receptors (TLRs) and IL-1 receptors. Upon receptor activation, IRAK4 phosphorylates IRAK1, leading to NF-kB and MAPK activation, which triggers inflammatory cytokine production. Mutations in IRAK4 cause primary immunodeficiency characterized by recurrent pyogenic bacterial infections, particularly in childhood. The gene is also implicated in cancer, where its expression may influence tumor progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Recurrent invasive pneumococcal disease | Loss-of-function mutations impair TLR/IL-1R signaling, reducing innate immune response | ClinVar, OMIM |
| IRAK4 deficiency | Homozygous or compound heterozygous mutations lead to absence of functional protein | OMIM, ClinVar |
| Pyogenic bacterial infections | Defective NF-kB activation and cytokine production in response to bacterial stimuli | OMIM |
| Cancer (potential) | Altered IRAK4 expression may affect tumor microenvironment and inflammation | COSMIC, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 10.2 | Medium |
| Spleen | 8.5 | Medium |
| Bone Marrow | 7.3 | Medium |
| Lymph Node | 6.8 | Low |
| Lung | 3.1 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 12.5 | High expression in myeloid cells |
| K-562 (lymphoblast) | 9.8 | Moderate expression |
| HeLa (cervical) | 2.3 | Low expression |
| A549 (lung) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.877C>T (p.Arg293*) | Nonsense | Rare | Loss of function, truncated protein |
| c.61A>G (p.Lys21Glu) | Missense | Rare | Kinase activity impaired |
| c.973G>A (p.Gly325Arg) | Missense | Rare | Disrupts kinase domain |
| c.114_115del (p.Gln39fs) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most IRAK4 mutations are loss-of-function, leading to impaired TLR/IL-1R signaling and immunodeficiency.
Gain of Function (GOF)
No gain-of-function mutations reported in IRAK4.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner, but inheritance is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein kinase activity | • ATP binding |
| • signal transduction | • innate immune response |
| • I-kappaB kinase/NF-kappaB signaling | • Toll-like receptor signaling pathway |
| • interleukin-1 receptor binding |
Pathways
• Toll-like receptor signaling pathway
• IL-1 signaling pathway
• MyD88-dependent pathway
• NF-kappaB signaling
• Innate Immune System
Protein Summary
IRAK4 is a 460-amino acid serine/threonine kinase with an N-terminal death domain and a central kinase domain. It is recruited to the receptor complex via MyD88, where it autophosphorylates and activates IRAK1. This leads to TRAF6 recruitment and downstream NF-kB and MAPK activation. The protein is essential for innate immune responses to bacterial pathogens. Defects cause recurrent infections, but patients often improve with age. In cancer, IRAK4 may promote inflammation-driven tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRAK4 Knockout HEK293 Cell Line | EDJ-KQ569 | Human | 51135 | Details Get a Quote |
| IRAK4 Knockout A-549 Cell Line | EDJ-KQ18964 | Human | 51135 | Details Get a Quote |
| IRAK4 Knockout HCT 116 Cell Line | EDJ-KQ18965 | Human | 51135 | Details Get a Quote |
| IRAK4 Knockout HeLa Cell Line | EDJ-KQ18966 | Human | 51135 | Details Get a Quote |
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