IRAK3
Chr 12interleukin 1 receptor associated kinase 3
Also known as: ASRT5, IRAKM
This gene encodes IRAK3, a putative inactive protein kinase that negatively regulates Toll-like receptor and IL-1 receptor signaling pathways in monocytes, macrophages, and dendritic cells by inhibiting IRAK1 and IRAK4 phosphorylation or stabilizing receptor complexes. Mutations are associated with asthma susceptibility and follow an autosomal dominant or complex inheritance pattern. The gene shows very low constraint against loss-of-function variants (pLI near zero, LOEUF 1.55), suggesting tolerance to such mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
IRAK3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools