IRAK3

Chr 12

interleukin 1 receptor associated kinase 3

Also known as: ASRT5, IRAKM

NCBI Gene: 11213ENSG00000090376UniProt: Q9Y616

This gene encodes a member of the interleukin-1 receptor-associated kinase protein family. Members of this family are essential components of the Toll/IL-R immune signal transduction pathways. This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of Toll-like receptor signaling. Mutations in this gene are associated with a susceptibility to asthma. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

{Asthma susceptibility 5}MIM #611064
UniProtAsthma-related traits 5
132
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— IRAK3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 96 VUS of 132 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.55LOEUF
pLI 0.000
Z-score -0.64
OE 1.14 (0.85–1.55)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.07Z-score
OE missense 1.01 (0.92–1.11)
315 obs / 311.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.14 (0.85–1.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 29 / 25.5Missense obs/exp: 315 / 311.3Syn Z: 0.64

ClinVar Variant Classifications

132 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS96
Likely Benign13
Benign6
Conflicting1
14
Pathogenic
2
Likely Pathogenic
96
VUS
13
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
1
0
1
0
2
VUS
2
88
6
0
96
Likely Benign
1
6
2
4
13
Benign
0
3
0
3
6
Conflicting
—1
Total497237132

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Asthma susceptibility 5}

MIM #611064

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
IRAK3 is upregulated in rheumatoid arthritis synovium and delays the onset of experimental arthritis.
Borghese F et al.·Front Immunol
2025
MYD88, IRAK3 and Rheumatoid Arthritis pathogenesis: Analysis of differential gene expression in CD14 + monocytes and the inflammatory cytokine levels.
Gomes da Silva IIF et al.·Immunobiology
2021
Methylation of IRAK3 is a novel prognostic marker in hepatocellular carcinoma.
Kuo CC et al.·World J Gastroenterol
2015
Host relieves lnc-IRAK3-3-sequestered miR-891b to attenuate apoptosis in Enterovirus 71 infection.
Liao YW et al.·Cell Microbiol
2019
IL-1 receptor-associated kinase-3 acts as an immune checkpoint in myeloid cells to limit cancer immunotherapy.
Tunalı G et al.·J Clin Invest
2023
At Least Two Genes Encode Many Variants of Irak3 in Rainbow Trout, but Neither the Full-Length Factor Nor Its Variants Interfere Directly With the TLR-Mediated Stimulation of Inflammation.
Rebl A et al.·Front Immunol
2019
Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis.
Sode J et al.·Pharmacogenomics J
2018
IL-1 signaling pathway molecules as key markers in childhood asthma.
Wei W et al.·Pediatr Allergy Immunol
2021
Crucial Genes in Aortic Dissection Identified by Weighted Gene Coexpression Network Analysis.
Zhang H et al.·J Immunol Res
2022
Crosstalk between oxidative stress and neutrophil response in early ischemic stroke: a comprehensive transcriptome analysis.
Mu C et al.·Front Immunol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools