IRAK2

Chr 3

interleukin 1 receptor associated kinase 2

Also known as: IRAK-2

NCBI Gene: 3656ENSG00000134070UniProt: O43187

IRAK2 encodes the interleukin-1 receptor-associated kinase 2, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. IRAK2 is reported to participate in the IL1-induced upregulation of NF-kappaB. [provided by RefSeq, Jul 2008]

172
ClinVar variants
53
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— IRAK2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 108 VUS of 172 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.
1.25LOEUF
pLI 0.000
Z-score 0.40
OE 0.92 (0.69–1.25)
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.
-0.06Z-score
OE missense 1.01 (0.93–1.10)
374 obs / 370.6 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.0.92 (0.69–1.25)
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 (0.93–1.10)
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.0.93
0≤1.21.6
LoF obs/exp: 30 / 32.4Missense obs/exp: 374 / 370.6Syn Z: 0.72

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic3
VUS108
Likely Benign10
Benign1
50
Pathogenic
3
Likely Pathogenic
108
VUS
10
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
50
0
50
Likely Pathogenic
0
0
3
0
3
VUS
0
95
13
0
108
Likely Benign
0
6
2
2
10
Benign
0
1
0
0
1
Total0102682172

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

View in ClinVar →

Protein Context — Lollipop Plot

IRAK2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
IRAK2-NF-κB signaling promotes glycolysis-dependent tumor growth in pancreatic cancer.
Yang J et al.·Cell Oncol (Dordr)
2022
IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.
Yu CC et al.·Int J Mol Sci
2023Cohort
IRAK2 and TLR10 confer risk of Hashimoto's disease: a genetic association study based on the Han Chinese population.
Li M et al.·J Hum Genet
2019
A coding IRAK2 protein variant compromises Toll-like receptor (TLR) signaling and is associated with colorectal cancer survival.
Wang H et al.·J Biol Chem
2014
A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.
Wang H et al.·Hepatology
2015Functional
Role of the Host Genetic Susceptibility to 2009 Pandemic Influenza A H1N1.
Pérez-Rubio G et al.·Viruses
2021Review
Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer.
Xu Y et al.·Int J Cancer
2018
Diminished expression of the ubiquitin-proteasome system in early treatment-naïve patients with rheumatoid arthritis and concomitant type 2 diabetes may be linked to IL-1 pathway hyper-activity; results from PEAC cohort.
Ruscitti P et al.·Arthritis Res Ther
2024Cohort
Interleukin-1 receptor-associated kinase-2 genetic variant rs708035 increases NF-κB activity through promoting TRAF6 ubiquitination.
Zhang W et al.·J Biol Chem
2014
RNA-Seq Analysis of Clinical Samples from TCGA Reveal Molecular Signatures for Ovarian Cancer.
Wadapurkar RM et al.·Cancer Invest
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Comprehensive pan-cancer characterization of IRAK2 as a potential prognostic biomarker and therapeutic target with validation in hepatocellular carcinoma.
Dong H et al.·BMC Cancer
2025🔓 Open Access
PD-L1 autoregulation promotes the proliferation, migration and invasion of glioblastoma cells via GP130/JAK2/STAT3/IRAK2/IL6 signaling pathway.
Xie X et al.·Sci Rep
2025🔓 Open Access
IRAK2 Ubiquitination Mediated by PELI1 Impairs Airway Epithelial Function and Accelerates Pediatric Asthma.
Wang S et al.·Am J Respir Cell Mol Biol
2025
Non-esterified fatty acids disrupt hepatic lipid metabolism and mitochondrial function via TLR4/MyD88/IRAK2 signaling in bovine hepatocytes.
Wen Y et al.·J Steroid Biochem Mol Biol
2025
IRAK2 overexpression restrains prostate cancer progression by regulation of TRAF6 ubiquitination.
Shi Y et al.·Cell Signal
2025
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