IRAK1 (Interleukin-1 Receptor Associated Kinase 1)
A key serine/threonine kinase in innate immune signaling, implicated in inflammatory diseases and cancer.
Gene Information Card
| Symbol | IRAK1 |
|---|---|
| Full Name | Interleukin-1 receptor associated kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 3654 ncbi.nlm.nih.gov/gene/3654 |
| Ensembl ID | ENSG00000184216 |
| UniProt ID | P51617 |
| OMIM ID | 300283 |
| HGNC ID | 6113 |
| Aliases | IRAK; IRAK-1; pelle |
Description
IRAK1 encodes a serine/threonine kinase that plays a critical role in the signaling pathways of Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R). Upon receptor activation, IRAK1 is recruited to the receptor complex via MyD88, undergoes phosphorylation, and subsequently activates TRAF6, leading to NF-kB and MAPK activation. This cascade is essential for innate immune responses and inflammation. IRAK1 also participates in other cellular processes, including apoptosis and cell survival. Dysregulation of IRAK1 has been linked to various inflammatory diseases, autoimmune disorders, and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked susceptibility to mycobacterial disease | Loss-of-function mutations impair TLR/IL-1R signaling, reducing cytokine production and immune defense. | ClinVar, OMIM |
| Rheumatoid arthritis | Increased IRAK1 expression and activity enhance inflammatory cytokine production, contributing to joint inflammation. | PubMed (via NCBI), OMIM |
| Systemic lupus erythematosus | Genetic variants in IRAK1 are associated with increased risk; altered signaling may promote autoimmunity. | OMIM, ClinVar |
| Prostate cancer | Overexpression of IRAK1 promotes tumor cell survival and proliferation via NF-kB activation. | COSMIC, PubMed (via NCBI) |
| Breast cancer | IRAK1 upregulation correlates with poor prognosis; it supports tumor growth through inflammatory signaling. | COSMIC, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 12.4 | Medium |
| Spleen | 10.2 | Medium |
| Lung | 8.5 | Low |
| Liver | 6.1 | Low |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; relevant for immune signaling studies |
| HeLa (cervical) | 8.7 | Moderate expression |
| A549 (lung) | 7.3 | Moderate expression |
| MCF7 (breast) | 6.8 | Low to moderate expression |
| K562 (leukemia) | 5.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.104C>T (p.Thr35Met) | Missense | Rare (0.01%) | May affect kinase activity; clinical significance uncertain |
| c.145G>A (p.Glu49Lys) | Missense | Rare (0.005%) | Potential impact on protein stability; reported in ClinVar |
| c.172C>T (p.Arg58Trp) | Missense | Rare (0.002%) | Associated with mycobacterial disease in one family; likely loss-of-function |
| c.221A>G (p.Asn74Ser) | Missense | Rare (0.001%) | Unknown effect; not reported in ClinVar |
| c.300del (p.Lys100fs) | Frameshift | Very rare | Predicted to cause loss-of-function; not observed in large cohorts |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair kinase activity or protein stability reduce TLR/IL-1R signaling, leading to immunodeficiency (e.g., X-linked susceptibility to mycobacterial disease).
Gain of Function (GOF)
Amplification or overexpression of IRAK1 (not point mutations) can enhance NF-kB signaling, promoting inflammation and tumorigenesis.
Dominant Negative (DN)
Some mutations may produce truncated proteins that interfere with wild-type IRAK1 function, but no confirmed dominant-negative variants are documented in ClinVar.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • signal transduction | • innate immune response |
| • inflammatory response | • NF-kappaB transcription factor activity |
| • protein phosphorylation | • Toll-like receptor signaling pathway |
| • interleukin-1 receptor binding |
Pathways
• Toll-like receptor signaling pathway
• Interleukin-1 signaling pathway
• MyD88-dependent cascade
• NF-kB activation
• MAPK signaling pathway
Protein Summary
IRAK1 is a 712-amino acid protein with an N-terminal death domain, a central kinase domain, and a C-terminal domain involved in interactions with TRAF6. It is activated by phosphorylation at multiple sites (e.g., Thr209, Thr387) upon receptor stimulation. The protein is ubiquitously expressed but most abundant in immune cells. It shuttles between the cytoplasm and nucleus, and its activity is regulated by phosphorylation, ubiquitination, and degradation. IRAK1 also interacts with other proteins such as MYD88, IRAK4, and TAK1 to propagate signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IRAK1 Knockout HEK293 Cell Line | EDJ-KQ3940 | Human | 3654 | Details Get a Quote |
| IRAK1BP1 Knockout HEK293 Cell Line | EDJ-KQ9348 | Human | 134728 | Details Get a Quote |
| IRAK1 Knockout A-549 Cell Line | EDJ-KQ26186 | Human | 3654 | Details Get a Quote |
| IRAK1 Knockout HCT 116 Cell Line | EDJ-KQ26187 | Human | 3654 | Details Get a Quote |
| IRAK1 Knockout HeLa Cell Line | EDJ-KQ26188 | Human | 3654 | Details Get a Quote |
| IRAK1BP1 Knockout A-549 Cell Line | EDJ-KQ35987 | Human | 134728 | Details Get a Quote |
| IRAK1BP1 Knockout HCT 116 Cell Line | EDJ-KQ35988 | Human | 134728 | Details Get a Quote |
| IRAK1BP1 Knockout HeLa Cell Line | EDJ-KQ35989 | Human | 134728 | Details Get a Quote |
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