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GeneE
27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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IRAK1
interleukin 1 receptor associated kinase 1
Chromosome X · Xq28
NCBI Gene: 3654Ensembl: ENSG00000184216.15HGNC: HGNC:6112UniProt: D3YTB5
391PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneKinase
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of leukocyte adhesion to vascular endothelial celltype I interferon-mediated signaling pathwayinterleukin-1-mediated signaling pathwayresponse to interleukin-1myelofibrosisprimary myelofibrosisneoplasmsystemic lupus erythematosus
✦AI Summary

IRAK1 is a serine/threonine protein kinase that functions as a critical initiator of innate immune responses through toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling 1. Upon TLR activation, IRAK1 is rapidly recruited by MYD88 adaptor protein, phosphorylated by IRAK4, and undergoes autophosphorylation to become catalytically active 2. Activated IRAK1 phosphorylates downstream targets including E3 ubiquitin ligases and interferon regulatory factor 7 (IRF7), culminating in NF-κB nuclear translocation and type I interferon production to establish antiviral immunity 3. In hematologic malignancies, IRAK1 acts as an oncogenic dependency: gain-of-function MYD88 mutations in diffuse large B-cell lymphoma (DLBCL) spontaneously activate IRAK1/IRAK4 signaling, promoting survival through sustained NF-κB and JAK-STAT3 activation 1. In glioma, radiation-induced IRAK1 expression mediates radioresistance by stabilizing the antioxidant enzyme PRDX1 and suppressing autophagic cell death 4. IRAK1 gene polymorphisms associate with inflammatory arthritis and ankylosing spondylitis susceptibility 56. These findings establish IRAK1 as both a fundamental innate immune signaling hub and an emerging therapeutic target in malignancy and inflammation 7.

Sources cited
1
IRAK1 is essential for ABC DLBCL survival and its activation by mutant MYD88 promotes NF-κB signaling, JAK kinase activation, and cytokine secretion
PMID: 21179087
2
Radiation induces IRAK1 expression which promotes radioresistance by preventing PRDX1 ubiquitination and autophagic cell death in glioma
PMID: 37031183
3
IRAK1 forms a complex with NFE2L1 and TRIM25 where TRIM25-mediated K63 polyubiquitination amplifies type I interferon responses in BCG-trained macrophages
PMID: 40178982
4
IRAK1 and IRAK4 operate at the nexus of inflammatory pathways in hematologic malignancies and represent emerging therapeutic targets
PMID: 34743084
5
IRAK1 gene polymorphisms (rs3027898) correlate with ankylosing spondylitis susceptibility and IRAK1 expression levels
PMID: 32572893
6
IRAK1 rs3027898 polymorphism associates with inflammatory arthritis susceptibility including rheumatoid arthritis
PMID: 25269878
7
BAP1 inhibits sequential IRAK1/IRAK4 activation by preventing IRAK4-mediated IRAK1 phosphorylation and NF-κB signaling in pancreatic cancer
PMID: 40083694
Disease Associationsⓘ20
myelofibrosisOpen Targets
0.49Moderate
primary myelofibrosisOpen Targets
0.48Moderate
neoplasmOpen Targets
0.40Weak
systemic lupus erythematosusOpen Targets
0.38Weak
neurodegenerative diseaseOpen Targets
0.38Weak
polycythemia veraOpen Targets
0.37Weak
multiple myelomaOpen Targets
0.37Weak
neuroinflammatory disorderOpen Targets
0.37Weak
Rett syndromeOpen Targets
0.33Weak
rheumatoid arthritisOpen Targets
0.27Weak
autoimmune diseaseOpen Targets
0.19Weak
ACPA-positive rheumatoid arthritisOpen Targets
0.15Weak
Apneic episodes in infancyOpen Targets
0.12Weak
cleft palateOpen Targets
0.12Weak
Fetal distressOpen Targets
0.12Weak
High palateOpen Targets
0.12Weak
Inguinal herniaOpen Targets
0.12Weak
Unilateral ptosisOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
leukemiaOpen Targets
0.11Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
PACRITINIBApproved
Activin receptor type-1 inhibitor
myelofibrosis
PACRITINIB CITRATEApproved
Activin receptor type-1 inhibitor
polycythemia vera
Related Genes
TAB3Protein interaction100%IKBKGProtein interaction100%TAB2Protein interaction100%PPP2R1AProtein interaction100%PPP2R2AProtein interaction100%PPP2R1BProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
86%
Liver
59%
Brain
38%
Ovary
37%
Heart
25%
Gene Interaction Network
Click a node to explore
IRAK1TAB3IKBKGTAB2PPP2R1APPP2R2APPP2R1B
PROTEIN STRUCTURE
Preparing viewer…
PDB6BFN · 2.26 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.32Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.18 [0.11–0.32]
RankingsWhere IRAK1 stands among ~20K protein-coding genes
  • #756of 20,598
    Most Researched391 · top 5%
  • #520of 1,025
    FDA-Approved Drug Targets2
  • #1,256of 17,882
    Most Constrained (LOEUF)0.32 · top 10%
Genes detectedIRAK1
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
Oncogenically active MYD88 mutations in human lymphoma.
PMID: 21179087
Nature · 2011
1.00
2
Radiation induces IRAK1 expression to promote radioresistance by suppressing autophagic cell death via decreasing the ubiquitination of PRDX1 in glioma cells.
PMID: 37031183
Cell Death Dis · 2023
0.90
3
MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1.
PMID: 36775818
Signal Transduct Target Ther · 2023
0.80
4
Identification of VISTA regulators in macrophages mediating cancer cell survival.
PMID: 39602545
Sci Adv · 2024
0.72
5
IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.
PMID: 34743084
Curr Opin Hematol · 2022
0.70