IRAK3
gene geneOn this page
Also known as IRAK-M
Summary
IRAK3 (interleukin 1 receptor associated kinase 3, HGNC:17020) is a protein-coding gene on chromosome 12q14.3, encoding Interleukin-1 receptor-associated kinase 3 (Q9Y616). Putative inactive protein kinase which regulates signaling downstream of immune receptors including IL1R and Toll-like receptors.
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.
Source: NCBI Gene 11213 — RefSeq curated summary.
At a glance
- Gene–disease (curated): asthma-related traits, susceptibility to, 5 (Limited, GenCC)
- GWAS associations: 3
- Clinical variants (ClinVar): 129 total — 2 likely-pathogenic
- Druggable target: yes — 35 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_007199
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:17020 |
| Approved symbol | IRAK3 |
| Name | interleukin 1 receptor associated kinase 3 |
| Location | 12q14.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | IRAK-M |
| Ensembl gene | ENSG00000090376 |
| Ensembl biotype | protein_coding |
| OMIM | 604459 |
| Entrez | 11213 |
Gene structure
Transcript identifiers
Ensembl transcripts: 7 — 7 protein_coding
ENST00000261233, ENST00000457197, ENST00000545837, ENST00000854785, ENST00000854786, ENST00000947373, ENST00000947374
RefSeq mRNA: 2 — MANE Select: NM_007199
NM_001142523, NM_007199
CCDS: CCDS44937, CCDS8975
Canonical transcript exons
ENST00000261233 — 12 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000871820 | 66203711 | 66203893 |
| ENSE00000871821 | 66209456 | 66209520 |
| ENSE00000871822 | 66210147 | 66210201 |
| ENSE00000871825 | 66211446 | 66211597 |
| ENSE00000871827 | 66217171 | 66217235 |
| ENSE00000871829 | 66226723 | 66226837 |
| ENSE00000871830 | 66228252 | 66228370 |
| ENSE00000871832 | 66244486 | 66244684 |
| ENSE00000871833 | 66244948 | 66245010 |
| ENSE00000871834 | 66245098 | 66245262 |
| ENSE00000871835 | 66247695 | 66254622 |
| ENSE00002237551 | 66189214 | 66189432 |
Expression profiles
Bgee: expression breadth ubiquitous, 238 present calls, max score 94.76.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1391 / max 2573.3421, expressed in 1183 samples.
FANTOM5 promoters (5 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 126544 | 16.6855 | 1182 |
| 126546 | 0.8425 | 104 |
| 126545 | 0.4489 | 81 |
| 126547 | 0.0954 | 28 |
| 126548 | 0.0669 | 20 |
Top tissues by expression
284 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| monocyte | CL:0000576 | 94.76 | gold quality |
| mononuclear cell | CL:0000842 | 94.17 | gold quality |
| leukocyte | CL:0000738 | 93.74 | gold quality |
| bone marrow | UBERON:0002371 | 90.98 | gold quality |
| parietal pleura | UBERON:0002400 | 90.75 | gold quality |
| blood | UBERON:0000178 | 90.14 | gold quality |
| right lung | UBERON:0002167 | 89.84 | gold quality |
| bone marrow cell | CL:0002092 | 89.68 | gold quality |
| bone element | UBERON:0001474 | 89.05 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 88.42 | gold quality |
| pleura | UBERON:0000977 | 88.05 | gold quality |
| spleen | UBERON:0002106 | 87.89 | gold quality |
| lower lobe of lung | UBERON:0008949 | 87.81 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 87.16 | gold quality |
| calcaneal tendon | UBERON:0003701 | 86.66 | gold quality |
| omental fat pad | UBERON:0010414 | 86.55 | gold quality |
| peritoneum | UBERON:0002358 | 86.45 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 86.37 | gold quality |
| upper lobe of lung | UBERON:0008948 | 85.39 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 85.37 | gold quality |
| granulocyte | CL:0000094 | 85.27 | gold quality |
| visceral pleura | UBERON:0002401 | 84.76 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 84.21 | gold quality |
| lung | UBERON:0002048 | 84.06 | gold quality |
| adipose tissue | UBERON:0001013 | 83.88 | gold quality |
| connective tissue | UBERON:0002384 | 83.62 | gold quality |
| epithelium of nasopharynx | UBERON:0001951 | 82.91 | gold quality |
| left uterine tube | UBERON:0001303 | 82.07 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 81.94 | gold quality |
| pericardium | UBERON:0002407 | 81.40 | gold quality |
Single-cell (SCXA)
Detected in 3 experiment(s), a significant marker in 2.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-CURD-119 | yes | 25.52 |
| E-ANND-3 | yes | 21.25 |
| E-CURD-11 | no | 101.69 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): ATF3, JUN, NR3C1, STAT3
miRNA regulators (miRDB)
210 targeting IRAK3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-450A-1-3P | 100.00 | 69.33 | 1837 |
| HSA-MIR-3646 | 100.00 | 73.56 | 5283 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-432-3P | 100.00 | 67.86 | 705 |
| HSA-MIR-6740-5P | 100.00 | 65.64 | 932 |
| HSA-MIR-4713-3P | 100.00 | 65.92 | 505 |
| HSA-MIR-3134 | 100.00 | 66.43 | 777 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-340-5P | 100.00 | 72.50 | 4437 |
| HSA-MIR-6873-3P | 100.00 | 71.42 | 2626 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-4534 | 99.99 | 66.58 | 1907 |
| HSA-MIR-3662 | 99.99 | 73.82 | 5684 |
| HSA-MIR-6077 | 99.99 | 68.04 | 2299 |
| HSA-MIR-449A | 99.99 | 71.05 | 1776 |
| HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 |
| HSA-MIR-524-5P | 99.98 | 73.43 | 4882 |
| HSA-MIR-4775 | 99.98 | 75.00 | 6394 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-12136 | 99.98 | 72.81 | 5713 |
| HSA-MIR-5696 | 99.98 | 72.36 | 4487 |
| HSA-MIR-607 | 99.97 | 73.62 | 5593 |
| HSA-MIR-302C-5P | 99.97 | 72.56 | 3642 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-3148 | 99.97 | 75.06 | 6478 |
| HSA-MIR-1250-3P | 99.96 | 70.04 | 4038 |
| HSA-MIR-3605-5P | 99.96 | 67.12 | 932 |
Literature-anchored findings (GeneRIF, showing 40)
- Identification and characterization of murine IRAK-M (PMID:12054681)
- Thus, our data indicate that IRAK-M could play a pivotal role in the process of endotoxin tolerance in human monocytes and provide evidence that PI3K is involved in regulating its expression. (PMID:14592437)
- IRAK-M is rapidly upregulated in human monocytes pre-exposed to tumor cells and could be involved in deactivation of tumor-infiltrating monocytes mediated by tumor cells. (PMID:15728517)
- These findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1. (PMID:17379480)
- IRAK-M is involved in the pathogenesis of early-onset persistent asthma. (PMID:17503328)
- no evidence to suggest association between inflammatory bowel disease, Crohn’s disease (CD), ulcerative colitis (UC) or subsets of CD & UC and IRAK-M; an interaction was found between IRAK-M and CARD15 in UC patients (PMID:17558906)
- LPS tolerance in human endotoxemia models is associated with IRAK-M up-regulation. (PMID:17982103)
- Porphyromonas gingivalis lipopolysaccharide upregulates IRAK-M in macrophages. (PMID:18156187)
- observed striking up-regulation of IRAK-M in monocytes, but without concomitant proinflammatory cytokine production (PMID:18354163)
- Analysis of single single nucleotide polymorphisms and haplotypes did not reveal a significant association between polymorphisms in the IRAK-M gene and atopic dermatitis in this cohort. (PMID:19013233)
- Immunosuppression in sepsis caused by B. pseudomallei is associated with an upregulation of IRAK-M and an indicator of poor outcome. (PMID:19114913)
- IRAK-M is a major mediator of globular adiponectin-induced endotoxin tolerance in primary macrophages (PMID:19414798)
- Nine SNPs distributed across eight genetic regions (ALOX5, IRAK3, ITGB2, NCF2, NFKB1, SELP, SOD1, and STAT1) were associated with risk of glioma with P value of <0.01. (PMID:19423540)
- inhibition of LPS-induced NFKB and ERK activation by acute alcohol leads to hyporesponsiveness of monocytes to LPS due to increased IRAK-M; chronic alcohol sensitizes monocytes to LPS through decreased IRAK-M expression and activation of NFKB and ERK (PMID:19561104)
- Intact IRAK-M is strongly expressed in resting human alveolar macrophages but is cleaved in patients with pneumonia via neutrophil-mediated induction of caspase-6 (CASP-6) activity. (PMID:21098228)
- Data demonstrates that TGF-beta-dependent induction of IRAK-M expression is an important, clinically relevant mechanism by which tumors may circumvent anti-tumor responses of macrophages. (PMID:21278795)
- Common SNPs in the IRAK3 gene may be determinants of sepsis-induced acute lung injury. (PMID:21297081)
- The upregulation of IRAK-M in macrophages is involved in the local immunosuppression around implants, and may contribute to septic and aseptic implant loosening. (PMID:21987497)
- The results confirm the importance of the IRAK3 in asthma pathogenesis in the European populations (PMID:22070913)
- these data indicate that epithelial IRAK-M overexpression in T(H)2 cytokine-exposed airways inhibits TLR2 signaling, providing a novel mechanism for the increased susceptibility of infections in asthmatic patients. (PMID:22154382)
- Data suggest further evaluation of IRAK3 as a diagnostic and prognostic marker, and as a target for intervention. (PMID:22272346)
- the tested variations of IRAK-M and SIGIRR genes do not confer a relevant role in the susceptibility to systemic lupus erythematosus in European-descent populations (PMID:22634523)
- these data identify an important signaling regulator in human macrophages that is used by surfactant to control the long-term alveolar inflammatory response, i.e., enhanced IRAK-M activity. (PMID:22886503)
- IRAK-M mediates TLR7-induced MEKK3-dependent second wave NFjB activation to produce inhibitory molecules (PMID:23376919)
- our study demonstrates that patients carrying IRAK-M+22148 G haplotype are more susceptible to sepsis than patients carrying IRAK-M+22148 A haplotype, suggesting that IRAK-M+22148 G haplotype might be a risk factor for sepsis. (PMID:23588345)
- These data indicate the enhancing effect of IRAK-M on epithelial human rhinovirus-16 infection, which is partly through the autophagic pathway. (PMID:24074582)
- The structure function of the death domain of human IRAK-M (PMID:25481771)
- IRAK-M expression is upregulated in peripheral blood cells from idiopathic pulmonary fibrosis patients (PMID:25595781)
- HIF1alpha is a regulator of monocyte functional re-programming in sepsis via regulating IRAKM expression. (PMID:25746953)
- IRAK3 methylation was associated with tumor stage and poor prognosis of hepatocellular carcinoma patients. (PMID:25852282)
- Alpha-Melanocyte-Stimulating Hormone Suppresses TLR2-Mediated Functional Responses through IRAK-M in Normal Human Keratinocytes (PMID:26309029)
- Data indicate a strong positive correlation between interleukin-1 receptor-associated kinase 3 (IRAK-M) and pSTAT3 protein in colorectal cancer (CRC). (PMID:27150039)
- Rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response. (PMID:27698401)
- IRAK-M functions to modulate inflammatory signaling pathways and is critical in maintaining immune system homeostasis in the gut. However, increased IRAK-M is associated with increased disease pathogenesis and increased cancer severity in human patients. (PMID:27939424)
- MERS-CoV S protein binds to DPP4 to suppress macrophage activation via induction of IRAK-M, PPARgamma and the immunosuppressive cytokine IL-10. (PMID:28118607)
- Clinical trial with house dust mite allergen challenge of asthmatic patients reveal that IRAK-M is a PIN1 target critical for IL-33 signaling in allergic asthma. NMR analysis and docking simulations suggest that PIN1 might regulate IRAK-M conformation and function in IL-33 signaling. (PMID:29686383)
- Study determined that the expression of a novel circRNA, circIRAK3, was increased in metastatic breast cancer (BC) cells and predictive of BC recurrence and identified miR-3607 as a circIRAK3-associated miRNA. FOXC1 the target of miR-3607, was downregulated in circIRAK3-silenced cells and mediated circIRAK3-induced BC cell migration. FOXC1 in turn could bind to the IRAK3 promoter, triggering a positive-feedback loop. (PMID:29803789)
- TLR stimulation led to IRAKM-caspase-8-ASC complex formation, resulting in the activation of caspase-8 and IL-1beta release in microglia. (PMID:30372424)
- Findings demonstrated a distinctive role of IRAK-M in maintaining chronic Th2 airway inflammation and indicated a complex role for IRAK-M in the initiation and progression of experimental allergic asthma. (PMID:30617222)
- IRAK3 modulates downstream innate immune signalling through its guanylate cyclase activity. (PMID:31664109)
Cross-species orthologs
9 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | irak3 | ENSDARG00000053131 |
| mus_musculus | Irak3 | ENSMUSG00000020227 |
| rattus_norvegicus | Irak3 | ENSRNOG00000004226 |
| drosophila_melanogaster | pll | FBGN0010441 |
| drosophila_melanogaster | Haspin | FBGN0046706 |
| caenorhabditis_elegans | WBGENE00004029 | |
| caenorhabditis_elegans | hasp-1 | WBGENE00007258 |
| caenorhabditis_elegans | WBGENE00012159 | |
| caenorhabditis_elegans | hasp-2 | WBGENE00021214 |
Paralogs (4): IRAK2 (ENSG00000134070), HASPIN (ENSG00000177602), IRAK1 (ENSG00000184216), IRAK4 (ENSG00000198001)
Protein
Protein identifiers
Interleukin-1 receptor-associated kinase 3 — Q9Y616 (reviewed: Q9Y616)
Alternative names: IL-1 receptor-associated kinase M, Inactive IL-1 receptor-associated kinase 3
All UniProt accessions (2): Q9Y616, F5GYN6
UniProt curated annotations — full annotation on UniProt →
Function. Putative inactive protein kinase which regulates signaling downstream of immune receptors including IL1R and Toll-like receptors. Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex. Upon IL33-induced lung inflammation, positively regulates expression of IL6, CSF3, CXCL2 and CCL5 mRNAs in dendritic cells.
Subunit / interactions. Monomer. Homodimer; disulfide-linked. May interact with IRAK4 (when phosphorylated). Interacts (when phosphorylated at Ser-110) with PIN1 (via WW domain) in response to IL33-mediated (but not TLR4 ligand LPS) dendritic cell stimulation.
Subcellular location. Cytoplasm. Nucleus.
Tissue specificity. Expressed in eosinophils, dendritic cells and/or monocytes (at protein level). Expressed predominantly in peripheral blood lymphocytes.
Disease relevance. Asthma-related traits 5 (ASRT5) [MIM:611064] Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, dyspnea, bronchial hyperresponsiveness as assessed by methacholine challenge test, serum IgE levels, atopy and atopic dermatitis. Disease susceptibility is associated with variants affecting the gene represented in this entry.
Domain organisation. The nucleotide binding domain binds ATP with low affinity.
Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9Y616-1 | 1 | yes |
| Q9Y616-2 | 2 |
RefSeq proteins (2): NP_001135995, NP_009130* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000488 | Death_dom | Domain |
| IPR000719 | Prot_kinase_dom | Domain |
| IPR011009 | Kinase-like_dom_sf | Homologous_superfamily |
| IPR011029 | DEATH-like_dom_sf | Homologous_superfamily |
| IPR042698 | IRAK3_PK | Domain |
| IPR042747 | IRAK3_death | Domain |
Pfam: PF00069, PF00531
UniProt features (73 total): helix 22, sequence variant 15, strand 14, mutagenesis site 5, binding site 4, domain 2, modified residue 2, disulfide bond 2, turn 2, chain 1, splice variant 1, region of interest 1, sequence conflict 1, site 1
Structure
Experimental structures (PDB)
3 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 6ZIW | X-RAY DIFFRACTION | 2.18 |
| 6RUU | X-RAY DIFFRACTION | 2.95 |
| 5UKE | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9Y616-F1 | 71.79 | 0.40 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1): 110–111 (cis/trans isomerization of proline peptide bond; by pin1; dependent on ser-110 phosphorylation)
Ligand- & substrate-binding residues (4): 171–179; 192; 295–298; 311
Post-translational modifications (2): 467, 110
Disulfide bonds (2): 202, 287
Mutagenesis-validated functional residues (5):
| Position | Phenotype |
|---|---|
| 110 | abolishes phosphorylation. abolishes interaction with pin1. reduces protein stability. |
| 110 | phosphomimic. slight decrease in the interaction with pin1. weak interaction with pin1 in absence of il33-mediated dendr |
| 210 | abolishes dimerization. |
| 214 | enhances dimerization. |
| 467 | no effect on the interaction with pin1. |
Function
Pathways and Gene Ontology
Reactome pathways
12 pathways
| ID | Pathway |
|---|---|
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane |
| R-HSA-9020702 | Interleukin-1 signaling |
| R-HSA-1280215 | Cytokine Signaling in Immune system |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade |
| R-HSA-168249 | Innate Immune System |
| R-HSA-168256 | Immune System |
| R-HSA-168898 | Toll-like Receptor Cascades |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade |
| R-HSA-446652 | Interleukin-1 family signaling |
| R-HSA-449147 | Signaling by Interleukins |
MSigDB gene sets: 305 (showing top):
GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_TOLERANCE_INDUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, CHUNG_BLISTER_CYTOTOXICITY_DN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, PID_IL1_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY
GO Biological Process (30): positive regulation of cytokine production (GO:0001819), negative regulation of cytokine-mediated signaling pathway (GO:0001960), MyD88-dependent toll-like receptor signaling pathway (GO:0002755), protein phosphorylation (GO:0006468), Toll signaling pathway (GO:0008063), response to virus (GO:0009615), positive regulation of macrophage tolerance induction (GO:0010933), negative regulation of macrophage cytokine production (GO:0010936), cytokine-mediated signaling pathway (GO:0019221), lipopolysaccharide-mediated signaling pathway (GO:0031663), response to peptidoglycan (GO:0032494), response to lipopolysaccharide (GO:0032496), negative regulation of interleukin-12 production (GO:0032695), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of toll-like receptor signaling pathway (GO:0034122), intracellular signal transduction (GO:0035556), negative regulation of protein catabolic process (GO:0042177), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), negative regulation of protein-containing complex disassembly (GO:0043242), regulation of protein-containing complex disassembly (GO:0043244), response to exogenous dsRNA (GO:0043330), negative regulation of MAPK cascade (GO:0043409), negative regulation of innate immune response (GO:0045824), interleukin-1-mediated signaling pathway (GO:0070498), response to interleukin-1 (GO:0070555), positive regulation of immune system process (GO:0002684), signal transduction (GO:0007165), regulation of innate immune response (GO:0045088)
GO Molecular Function (9): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein kinase binding (GO:0019901), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515)
GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886)
Reactome top-level categories
Rollup of top-10 pathways:
| Category | Pathways |
|---|---|
| Immune System | 2 |
| Toll-like Receptor Cascades | 2 |
| Toll Like Receptor 2 (TLR2) Cascade | 2 |
| Toll Like Receptor 4 (TLR4) Cascade | 1 |
| Toll Like Receptor TLR1:TLR2 Cascade | 1 |
| Toll Like Receptor TLR6:TLR2 Cascade | 1 |
| Interleukin-1 family signaling | 1 |
| Innate Immune System | 1 |
| Signaling by Interleukins | 1 |
| Cytokine Signaling in Immune system | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cell surface receptor signaling pathway | 3 |
| negative regulation of signal transduction | 2 |
| toll-like receptor signaling pathway | 2 |
| response to molecule of bacterial origin | 2 |
| response to oxygen-containing compound | 2 |
| negative regulation of cytokine production | 2 |
| intracellular anatomical structure | 2 |
| canonical NF-kappaB signal transduction | 2 |
| regulation of canonical NF-kappaB signal transduction | 2 |
| protein dimerization activity | 2 |
| cytokine production | 1 |
| regulation of cytokine production | 1 |
| positive regulation of gene expression | 1 |
| positive regulation of multicellular organismal process | 1 |
| regulation of cytokine-mediated signaling pathway | 1 |
| cytokine-mediated signaling pathway | 1 |
| negative regulation of response to cytokine stimulus | 1 |
| phosphorylation | 1 |
| protein modification process | 1 |
| response to other organism | 1 |
| positive regulation of tolerance induction | 1 |
| macrophage tolerance induction | 1 |
| regulation of macrophage tolerance induction | 1 |
| negative regulation of cytokine production involved in immune response | 1 |
| macrophage cytokine production | 1 |
| regulation of macrophage cytokine production | 1 |
| cellular response to cytokine stimulus | 1 |
| cellular response to lipopolysaccharide | 1 |
| response to nitrogen compound | 1 |
| response to lipid | 1 |
| interleukin-12 production | 1 |
| regulation of interleukin-12 production | 1 |
| interleukin-6 production | 1 |
| regulation of interleukin-6 production | 1 |
| tumor necrosis factor production | 1 |
| regulation of tumor necrosis factor production | 1 |
| negative regulation of tumor necrosis factor superfamily cytokine production | 1 |
| negative regulation of immune system process | 1 |
| regulation of toll-like receptor signaling pathway | 1 |
| signal transduction | 1 |
Protein interactions and networks
STRING
2322 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| IRAK3 | IRAK1 | P51617 | 984 |
| IRAK3 | IRAK2 | O43187 | 974 |
| IRAK3 | IRAK4 | Q9NWZ3 | 947 |
| IRAK3 | MYD88 | P78397 | 924 |
| IRAK3 | TRAF6 | Q9Y4K3 | 863 |
| IRAK3 | SIGIRR | Q6IA17 | 843 |
| IRAK3 | IL1R1 | P14778 | 781 |
| IRAK3 | TLR4 | O00206 | 774 |
| IRAK3 | TLR2 | O60603 | 770 |
| IRAK3 | INPP5D | Q92835 | 736 |
| IRAK3 | TOLLIP | Q9H0E2 | 707 |
| IRAK3 | TLR5 | O60602 | 664 |
| IRAK3 | TLR9 | Q9NR96 | 660 |
| IRAK3 | TLR3 | O15455 | 647 |
| IRAK3 | TLR8 | Q9NR97 | 645 |
IntAct
33 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| TRAF6 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.680 |
| IRAK3 | TRAF6 | psi-mi:“MI:0915”(physical association) | 0.680 |
| IRAK1 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.560 |
| IRAK2 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.560 |
| IRAK3 | IRAK1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| IRAK3 | IRAK2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| IRAK3 | IRAK2 | psi-mi:“MI:0914”(association) | 0.560 |
| IRAK3 | CD14 | psi-mi:“MI:0915”(physical association) | 0.440 |
| IRAK3 | HOXB7 | psi-mi:“MI:0915”(physical association) | 0.440 |
| IRAK3 | CD14 | psi-mi:“MI:0403”(colocalization) | 0.440 |
| HOXB7 | IRAK3 | psi-mi:“MI:0403”(colocalization) | 0.440 |
| IRAK3 | KRT8 | psi-mi:“MI:0915”(physical association) | 0.400 |
| IRAK3 | KRT18 | psi-mi:“MI:0915”(physical association) | 0.400 |
| IRAK3 | MYD88 | psi-mi:“MI:0915”(physical association) | 0.400 |
| IRAK3 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.400 |
| TICAM2 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.400 |
| HSP90AB1 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.400 |
| ATP6V0B | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.370 |
| IRAK3 | COPB1 | psi-mi:“MI:0915”(physical association) | 0.370 |
| IRAK3 | ECM1 | psi-mi:“MI:0915”(physical association) | 0.370 |
| FOLR1 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.370 |
| IRAK3 | CDCA5 | psi-mi:“MI:0915”(physical association) | 0.370 |
| IRAK3 | ADH1B | psi-mi:“MI:0915”(physical association) | 0.370 |
| NONO | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.370 |
| NTRK3 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.370 |
| LDB1 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.370 |
| NSA2 | IRAK3 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ABL1 | psi-mi:“MI:0914”(association) | 0.350 | |
| IRAK3 | H2AZ1 | psi-mi:“MI:0914”(association) | 0.350 |
| IRAK3 | CD44 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (35): TRAF6 (Two-hybrid), IRAK3 (Proximity Label-MS), IRAK3 (Proximity Label-MS), IRAK3 (Affinity Capture-Western), IRAK3 (Affinity Capture-Western), RNF152 (Affinity Capture-Western), IRAK3 (Proximity Label-MS), IRAK3 (Affinity Capture-Western), CD44 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), TBK1 (Affinity Capture-MS), HSPB8 (Affinity Capture-MS), H2AFZ (Affinity Capture-MS), HIST2H2AC (Affinity Capture-MS)
ESM2 similar proteins: A4Q9F4, A6QLH5, D3Z7P3, D3ZVU9, E9PV86, M0R7T9, O35652, O43414, O54804, O60242, O60347, O70512, O94925, P08887, P0C7M8, P13264, P35790, P85298, Q01134, Q08DW9, Q13202, Q13505, Q2HJ53, Q2TBM7, Q3UGX3, Q4R766, Q4R7M4, Q58DH2, Q5XI70, Q62225, Q6AYT7, Q6DN14, Q80T74, Q80UW0, Q80ZF8, Q86W50, Q8C460, Q8N2K0, Q8NBA8, Q8NHH1
Diamond homologs: A0A0P0XII1, C0LGD7, C0LGG7, C0LGU1, C0LGU5, D7UPN3, F4JEQ2, F4JPX3, G5ECP4, O22187, O22476, O43187, O48814, O49839, O49840, O65472, O65530, O80719, O80939, P43293, P46573, P51617, P93050, Q05652, Q06548, Q0P5I2, Q0WRY5, Q1PDV6, Q1PDW3, Q1PE89, Q1PEM5, Q1RMT8, Q2LGB3, Q39086, Q3E9X6, Q3EDL4, Q5PP29, Q5R810, Q5WA76, Q5XF79
SIGNOR signaling
3 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| IRAK3 | down-regulates | IRAK4 | binding |
| NR3C1 | “up-regulates quantity” | IRAK3 | “transcriptional regulation” |
| IRAK3 | “down-regulates activity” | Inflammation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 6 | 54.4× | 1e-07 |
| MyD88 dependent cascade initiated on endosome | 6 | 54.4× | 1e-07 |
| Toll Like Receptor 7/8 (TLR7/8) Cascade | 5 | 43.9× | 4e-06 |
| Toll Like Receptor 9 (TLR9) Cascade | 5 | 41.8× | 5e-06 |
| MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 5 | 36.2× | 8e-06 |
| Toll Like Receptor 4 (TLR4) Cascade | 5 | 31.2× | 1e-05 |
| Toll-like Receptor Cascades | 5 | 29.6× | 2e-05 |
| Cytokine Signaling in Immune system | 5 | 9.7× | 1e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| toll-like receptor 4 signaling pathway | 6 | 131.7× | 2e-09 |
| positive regulation of type I interferon production | 5 | 87.8× | 4e-07 |
| positive regulation of canonical NF-kappaB signal transduction | 8 | 24.2× | 2e-07 |
| cellular response to lipopolysaccharide | 5 | 20.4× | 2e-04 |
| inflammatory response | 6 | 9.4× | 1e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
129 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 2 |
| Uncertain significance | 93 |
| Likely benign | 13 |
| Benign | 6 |
Top pathogenic / likely-pathogenic (2)
| Variant ID | HGVS | Classification |
|---|---|---|
| 423059 | NM_007199.3(IRAK3):c.1218_1219insTGA (p.Val407Ter) | Likely pathogenic |
| 503865 | NM_007199.3(IRAK3):c.1148dup (p.Arg384fs) | Likely pathogenic |
SpliceAI
2928 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 12:66203700:A:AG | acceptor_gain | 1.0000 |
| 12:66203701:A:G | acceptor_gain | 1.0000 |
| 12:66210144:TAG:T | acceptor_loss | 1.0000 |
| 12:66210145:A:AG | acceptor_gain | 1.0000 |
| 12:66210145:AGG:A | acceptor_loss | 1.0000 |
| 12:66210146:G:GG | acceptor_gain | 1.0000 |
| 12:66210198:AAAG:A | donor_loss | 1.0000 |
| 12:66210199:AAGG:A | donor_loss | 1.0000 |
| 12:66210200:AGG:A | donor_loss | 1.0000 |
| 12:66210201:GGTAT:G | donor_loss | 1.0000 |
| 12:66210202:G:GA | donor_loss | 1.0000 |
| 12:66210203:T:G | donor_loss | 1.0000 |
| 12:66211444:A:G | acceptor_gain | 1.0000 |
| 12:66217236:G:GG | donor_gain | 1.0000 |
| 12:66245095:AAGC:A | acceptor_gain | 1.0000 |
| 12:66245095:AAGCG:A | acceptor_gain | 1.0000 |
| 12:66189431:GG:G | donor_gain | 0.9900 |
| 12:66189432:GG:G | donor_gain | 0.9900 |
| 12:66189432:GGTG:G | donor_loss | 0.9900 |
| 12:66189433:G:GA | donor_loss | 0.9900 |
| 12:66189434:T:G | donor_loss | 0.9900 |
| 12:66190115:T:G | donor_gain | 0.9900 |
| 12:66209491:G:GT | donor_gain | 0.9900 |
| 12:66209492:A:T | donor_gain | 0.9900 |
| 12:66210142:CTTA:C | acceptor_loss | 0.9900 |
| 12:66210145:AG:A | acceptor_gain | 0.9900 |
| 12:66210146:GG:G | acceptor_gain | 0.9900 |
| 12:66211443:A:AG | acceptor_gain | 0.9900 |
| 12:66211443:AAG:A | acceptor_gain | 0.9900 |
| 12:66244550:C:CA | acceptor_gain | 0.9900 |
AlphaMissense
3948 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 12:66189420:T:A | W41R | 0.996 |
| 12:66189420:T:C | W41R | 0.996 |
| 12:66203834:T:C | L86P | 0.993 |
| 12:66245247:A:C | R433S | 0.990 |
| 12:66245247:A:T | R433S | 0.990 |
| 12:66189422:G:C | W41C | 0.988 |
| 12:66189422:G:T | W41C | 0.988 |
| 12:66228273:T:A | W264R | 0.988 |
| 12:66228273:T:C | W264R | 0.988 |
| 12:66245246:G:C | R433T | 0.988 |
| 12:66203806:G:C | A77P | 0.987 |
| 12:66189396:G:C | D33H | 0.986 |
| 12:66203776:A:C | S67R | 0.986 |
| 12:66203778:T:A | S67R | 0.986 |
| 12:66203778:T:G | S67R | 0.986 |
| 12:66203795:T:C | L73P | 0.986 |
| 12:66203846:T:C | L90P | 0.984 |
| 12:66228283:G:C | R267P | 0.984 |
| 12:66245221:T:C | C425R | 0.983 |
| 12:66189417:G:C | G40R | 0.982 |
| 12:66203783:C:A | T69K | 0.982 |
| 12:66203797:T:A | W74R | 0.980 |
| 12:66203797:T:C | W74R | 0.980 |
| 12:66244680:G:A | G361E | 0.979 |
| 12:66189430:T:C | L44P | 0.978 |
| 12:66245245:A:G | R433G | 0.978 |
| 12:66244673:A:C | S359R | 0.977 |
| 12:66244675:C:A | S359R | 0.977 |
| 12:66244675:C:G | S359R | 0.977 |
| 12:66211585:A:C | K192N | 0.976 |
dbSNP variants (sampled 300 via entrez): RS1000027530 (12:66236547 G>A), RS1000177646 (12:66235857 C>T), RS1000209533 (12:66238992 A>T), RS1000245350 (12:66187870 T>C), RS1000333745 (12:66242043 G>A,C,T), RS1000341406 (12:66232063 C>T), RS1000370917 (12:66219183 G>T), RS1000396243 (12:66224993 A>C), RS1000579389 (12:66222905 A>G), RS1000616881 (12:66229781 C>T), RS1000627962 (12:66235541 C>G), RS1000672279 (12:66231725 A>T), RS1000673079 (12:66230388 T>C), RS1000690764 (12:66229178 C>G), RS1000785344 (12:66228688 A>C)
Disease associations
OMIM: gene MIM:604459 | disease phenotypes: MIM:142623, MIM:611064
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| asthma-related traits, susceptibility to, 5 | Limited | Autosomal dominant |
Mondo (2): Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), asthma-related traits, susceptibility to, 5 (MONDO:0012607)
Orphanet (1): Hirschsprung disease (Orphanet:388)
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
3 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST002361_26 | Smooth-surface caries | 3.000000e-07 |
| GCST005976_21 | White blood cell count (basophil) | 2.000000e-10 |
| GCST011398_6 | Response to esketamine in treatment resistant depression | 4.000000e-08 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0005090 | basophil count |
| EFO:0009748 | response to ketamine |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (3): CHEMBL4742326 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748234 (PROTEIN-PROTEIN INTERACTION), CHEMBL5081 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 279,917 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1287853 | FEDRATINIB | 4 | 3,554 |
| CHEMBL2035187 | PACRITINIB | 4 | 3,345 |
| CHEMBL2103830 | FOSTAMATINIB | 4 | 3,841 |
| CHEMBL3301622 | GILTERITINIB | 4 | 2,395 |
| CHEMBL477772 | PAZOPANIB | 4 | 15,540 |
| CHEMBL502835 | NINTEDANIB | 4 | 8,545 |
| CHEMBL535 | SUNITINIB | 4 | 79,020 |
| CHEMBL601719 | CRIZOTINIB | 4 | 14,403 |
| CHEMBL608533 | MIDOSTAURIN | 4 | 7,259 |
| CHEMBL939 | GEFITINIB | 4 | 117,814 |
| CHEMBL2105728 | CRENOLANIB | 3 | 2,167 |
| CHEMBL31965 | CANERTINIB | 3 | 8,083 |
| CHEMBL603469 | LESTAURTINIB | 3 | |
| CHEMBL1230609 | FORETINIB | 2 | 3,096 |
| CHEMBL1236962 | OMIPALISIB | 2 | 3,989 |
| CHEMBL124660 | TANDUTINIB | 2 | 2,530 |
| CHEMBL1721885 | SU-014813 | 2 | 363 |
| CHEMBL1822792 | MK-2461 | 2 | 686 |
| CHEMBL1944698 | ZOTIRACICLIB | 2 | 2,915 |
| CHEMBL215152 | DEFOSBARASERTIB | 2 | 372 |
| CHEMBL475251 | R-406 | 2 | |
| CHEMBL521851 | PICTILISIB | 2 | |
| CHEMBL564829 | MILCICLIB | 2 | |
| CHEMBL572878 | TOZASERTIB | 2 | |
| CHEMBL1908394 | GSK-461364 | 1 | |
| CHEMBL1908397 | KW-2449 | 1 | |
| CHEMBL1952329 | SGI-1776 | 1 | |
| CHEMBL259084 | MLN-8054 | 1 | |
| CHEMBL296468 | BMS-387032 | 1 | |
| CHEMBL3544932 | TAK-901 | 1 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — Interleukin-1 receptor-associated kinase (IRAK) family
Most potent curated ligand interactions (1 total), top 1:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| IRAK3 PROTAC 23 | Binding | 8.3 | pIC50 |
Binding affinities (BindingDB)
12 measured of 12 human assays (12 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| Staurosporine | KD | 1.7 nM | |
| PKC-412 | KD | 190 nM | |
| 4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid | KD | 300 nM | |
| 4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide | KD | 740 nM | |
| N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide | KD | 1100 nM | |
| CI-1033 | KD | 1700 nM | |
| BMS-387072 | KD | 1800 nM | |
| GEFITINIB | IC50 | 2300 nM | US-9416123: Kinase modulators for the treatment of cancer |
| 5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide | KD | 2600 nM | |
| 5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide | KD | 2900 nM | |
| 1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b | KD | 3100 nM | |
| N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide | KD | 3500 nM |
ChEMBL bioactivities
106 potent at pChembl≥5 of 107 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.40 | IC50 | 4 | nM | CHEMBL4788568 |
| 8.40 | IC50 | 4 | nM | CHEMBL4763746 |
| 8.30 | IC50 | 5 | nM | CHEMBL4749646 |
| 8.22 | IC50 | 6 | nM | CHEMBL4744403 |
| 8.22 | IC50 | 6 | nM | CHEMBL4777817 |
| 8.22 | IC50 | 6 | nM | CHEMBL4798668 |
| 8.15 | Kd | 7 | nM | GILTERITINIB |
| 8.00 | IC50 | 10 | nM | CHEMBL4094760 |
| 8.00 | IC50 | 10 | nM | CHEMBL4779593 |
| 7.96 | Kd | 11 | nM | R-406 |
| 7.95 | Kd | 11.24 | nM | CHEMBL5653589 |
| 7.92 | Kd | 12 | nM | CHEMBL3688339 |
| 7.89 | IC50 | 13 | nM | CHEMBL4791281 |
| 7.89 | Kd | 13 | nM | STAUROSPORINE |
| 7.82 | IC50 | 15 | nM | CHEMBL4754560 |
| 7.80 | Kd | 16 | nM | LESTAURTINIB |
| 7.72 | IC50 | 19 | nM | CHEMBL4779139 |
| 7.68 | IC50 | 21 | nM | CHEMBL4762658 |
| 7.68 | IC50 | 21 | nM | CHEMBL4757434 |
| 7.68 | IC50 | 21 | nM | CHEMBL4747690 |
| 7.66 | IC50 | 22 | nM | CHEMBL4746543 |
| 7.62 | Kd | 24 | nM | MK-5108 |
| 7.62 | IC50 | 24 | nM | CHEMBL4763804 |
| 7.60 | IC50 | 25 | nM | CHEMBL4787051 |
| 7.58 | Kd | 26 | nM | SGI-1776 |
| 7.58 | ED50 | 26.22 | nM | CHEMBL5653589 |
| 7.57 | Kd | 27 | nM | TAK-901 |
| 7.57 | IC50 | 27 | nM | CHEMBL4064608 |
| 7.51 | IC50 | 31 | nM | CHEMBL4278882 |
| 7.51 | Kd | 31 | nM | CRIZOTINIB |
| 7.48 | IC50 | 33 | nM | CHEMBL4752190 |
| 7.48 | IC50 | 33 | nM | CHEMBL4753038 |
| 7.47 | IC50 | 34 | nM | CHEMBL4743058 |
| 7.47 | Kd | 34 | nM | CHEMBL4749646 |
| 7.46 | Kd | 35 | nM | PACRITINIB |
| 7.37 | Kd | 43 | nM | R-406 |
| 7.30 | IC50 | 50 | nM | CHEMBL4778668 |
| 7.29 | IC50 | 51 | nM | CHEMBL4750934 |
| 7.24 | Kd | 57 | nM | CYC-116 |
| 7.10 | Kd | 80 | nM | XL-228 |
| 7.03 | Kd | 93 | nM | CHEMBL4064608 |
| 6.92 | Kd | 120 | nM | FEDRATINIB |
| 6.83 | Kd | 147 | nM | LESTAURTINIB |
| 6.80 | Kd | 160 | nM | TAE-684 |
| 6.75 | Kd | 180 | nM | MIDOSTAURIN |
| 6.62 | Kd | 240 | nM | KW-2449 |
| 6.59 | Kd | 254 | nM | K-252A |
| 6.54 | Kd | 291 | nM | MILCICLIB |
| 6.54 | Kd | 286 | nM | ZOTIRACICLIB |
| 6.43 | Kd | 370 | nM | FORETINIB |
PubChem BioAssay actives
98 with measured affinity, of 538 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 2-(1-methyl-2,6-dioxopiperidin-3-yl)-5-[4-[2-[1-[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]piperidin-4-yl]ethyl]piperazin-1-yl]isoindole-1,3-dione | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0040 | uM |
| 1-[4-[4-[(5-propan-2-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]piperazin-1-yl]ethanone | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0040 | uM |
| 2-(2,6-dioxopiperidin-3-yl)-5-[4-[2-[1-[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]piperidin-4-yl]ethyl]piperazin-1-yl]isoindole-1,3-dione | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0050 | uM |
| 1-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]ethanone | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0060 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[7-[[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]amino]heptanoylamino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0060 | uM |
| 2-(2,6-dioxopiperidin-3-yl)-5-[4-[[1-[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]piperidin-4-yl]methyl]piperazin-1-yl]isoindole-1,3-dione | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0060 | uM |
| Gilteritinib | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0070 | uM |
| N-(4-morpholin-4-ylcyclohexyl)-5-(oxan-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0100 | uM |
| N-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]-4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0100 | uM |
| 6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one | 625066: Binding constant for IRAK3 kinase domain | kd | 0.0110 | uM |
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148602: Binding affinity to human IRAK3 incubated for 45 mins by Kinobead based pull down assay | kd | 0.0112 | uM |
| 1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0120 | uM |
| N-[4-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]butyl]-4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0130 | uM |
| (2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one | 435528: Binding constant for IRAK3 kinase domain | kd | 0.0130 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[4-[[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]amino]butanoylamino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0150 | uM |
| (15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one | 507570: Binding affinity to IRAK3 | kd | 0.0160 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-[2-[2-[2-[[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0190 | uM |
| N-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexyl]-4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0210 | uM |
| N-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]-4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0210 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-[2-[2-[2-oxo-2-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0210 | uM |
| N-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]-4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0220 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-[2-[[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0240 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-[2-[2-[[4-oxo-4-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]butanoyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0250 | uM |
| N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0260 | uM |
| 5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0270 | uM |
| Crizotinib | 625066: Binding constant for IRAK3 kinase domain | kd | 0.0310 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-[2-[2-[2-[2-[2-oxo-2-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0330 | uM |
| 2-(2,6-dioxopiperidin-3-yl)-4-[2-[2-[2-[2-[2-[3-oxo-3-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]propoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]isoindole-1,3-dione | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0330 | uM |
| 2-(2,6-dioxopiperidin-3-yl)-4-[2-[2-[2-[3-oxo-3-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]propoxy]ethoxy]ethoxy]ethylamino]isoindole-1,3-dione | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0340 | uM |
| Pacritinib | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0350 | uM |
| 2-(2,6-dioxopiperidin-3-yl)-4-[2-[2-[2-[2-[3-oxo-3-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]propoxy]ethoxy]ethoxy]ethoxy]ethylamino]isoindole-1,3-dione | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0500 | uM |
| (2S,4R)-1-[(2S)-3,3-dimethyl-2-[[2-[2-[2-[2-[2-[2-oxo-2-[4-[4-[(5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl)amino]cyclohexyl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]butanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide | 1723774: Inhibition of kinase tracer 236 binding to recombinant human full-length GST-tagged IRAK3 expressed in insect cells by Lanthascreen Eu kinase binding assay | ic50 | 0.0510 | uM |
| 4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0570 | uM |
| 4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.0800 | uM |
| Fedratinib | 625066: Binding constant for IRAK3 kinase domain | kd | 0.1200 | uM |
| 5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine | 625066: Binding constant for IRAK3 kinase domain | kd | 0.1600 | uM |
| Midostaurin | 435528: Binding constant for IRAK3 kinase domain | kd | 0.1800 | uM |
| [4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone | 625066: Binding constant for IRAK3 kinase domain | kd | 0.2400 | uM |
| methyl (15S,16R,18R)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-16-carboxylate | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.2540 | uM |
| (16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.2860 | uM |
| N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.2910 | uM |
| 1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide | 625066: Binding constant for IRAK3 kinase domain | kd | 0.3700 | uM |
| N-methyl-6-(trifluoromethyl)-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine | 1673297: Binding affinity to human wild type partial length IRAK3 (V147 to E596 residues) expressed in bacterial expression system by Kinomescan method | kd | 0.4800 | uM |
| 14-[[[(2R)-1,4-dioxan-2-yl]methyl-methylsulfamoyl]amino]-5-(1-methylpyrazol-4-yl)-2-oxo-7-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,9,12,14-heptaene | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.5020 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148602: Binding affinity to human IRAK3 incubated for 45 mins by Kinobead based pull down assay | kd | 0.5768 | uM |
| (3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one | 625066: Binding constant for IRAK3 kinase domain | kd | 0.6100 | uM |
| 4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide | 435528: Binding constant for IRAK3 kinase domain | kd | 0.7300 | uM |
| N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-[(6-fluoropyrazolo[1,5-a]pyrimidin-5-yl)amino]-4-(propan-2-ylamino)pyridine-3-carboxamide | 1664785: Inhibition of human wild type partial length IRAK3 (147 to 596 residues) expressed in bacterial expression system | ic50 | 0.7600 | uM |
| 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine | 1425028: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry. | kd | 0.7710 | uM |
| Pazopanib | 435528: Binding constant for IRAK3 kinase domain | kd | 0.8000 | uM |
CTD chemical–gene interactions
32 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | increases expression | 2 |
| Vehicle Emissions | decreases expression, decreases reaction, increases expression | 2 |
| Lipopolysaccharides | increases expression | 2 |
| aristolochic acid I | decreases expression | 1 |
| trichostatin A | increases expression | 1 |
| potassium chromate(VI) | affects cotreatment, decreases expression | 1 |
| epigallocatechin gallate | affects cotreatment, decreases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide | decreases expression, decreases reaction | 1 |
| incobotulinumtoxinA | increases expression | 1 |
| (+)-JQ1 compound | decreases expression | 1 |
| Norethindrone Acetate | affects cotreatment, increases expression | 1 |
| Acetaminophen | decreases expression | 1 |
| Air Pollutants | decreases expression, increases abundance | 1 |
| Allergens | increases expression | 1 |
| Benzo(a)pyrene | increases methylation | 1 |
| Diethylhexyl Phthalate | decreases expression | 1 |
| Doxorubicin | decreases expression | 1 |
| Estradiol | affects cotreatment, increases expression | 1 |
| Formaldehyde | decreases expression | 1 |
| Hyaluronic Acid | increases expression | 1 |
| Methyl Methanesulfonate | decreases expression | 1 |
| Progesterone | increases expression | 1 |
| Silicon Dioxide | increases methylation | 1 |
| Smoke | decreases expression, increases abundance | 1 |
| Tetradecanoylphorbol Acetate | affects cotreatment, affects expression | 1 |
| Tobacco Smoke Pollution | increases expression | 1 |
| Valproic Acid | increases expression | 1 |
| Vanadates | decreases expression | 1 |
| Zinc | affects cotreatment, affects expression | 1 |
ChEMBL screening assays
147 unique, capped per target: 147 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL4729440 | Binding | Protac activity at CRBN/IRAK3 in LPS-induced human THP1 cells assessed as induction of IRAK3 degradation at 1 uM by Western blot analysis relative to control | Discovery of Proteolysis-Targeting Chimera Molecules that Selectively Degrade the IRAK3 Pseudokinase. — J Med Chem |
Cellosaurus cell lines
3 cell lines: 3 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B9YE | Abcam THP-1 IRAK3 KO | Cancer cell line | Male |
| CVCL_E0FA | Ubigene HeLa IRAK3 KO | Cancer cell line | Female |
| CVCL_SS86 | HAP1 IRAK3 (-) | Cancer cell line | Male |
Clinical trials (associated diseases)
48 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT02343562 | PHASE4 | UNKNOWN | Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis |
| NCT07186647 | PHASE4 | COMPLETED | Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques |
| NCT04904081 | PHASE3 | UNKNOWN | Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery |
| NCT00630838 | PHASE2 | COMPLETED | Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC) |
| NCT01985646 | EARLY_PHASE1 | COMPLETED | A Trial on Conservative Treatment for Infants’ Hirschsprung Disease |
| NCT00478712 | Not specified | RECRUITING | Hirschsprung Disease Genetic Study |
| NCT01515501 | Not specified | COMPLETED | Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial) |
| NCT01793168 | Not specified | RECRUITING | Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford |
| NCT01927809 | Not specified | UNKNOWN | Genetic Mosaicism in Hirschsprung’s Disease |
| NCT02193685 | Not specified | UNKNOWN | Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease |
| NCT02216994 | Not specified | UNKNOWN | A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study |
| NCT02296008 | Not specified | COMPLETED | 3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders |
| NCT02776176 | Not specified | UNKNOWN | Enhanced Recovery After Surgery In Hirschsprung Disease |
| NCT02857205 | Not specified | COMPLETED | MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis |
| NCT03269812 | Not specified | UNKNOWN | Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease |
| NCT03666767 | Not specified | COMPLETED | Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries |
| NCT04020939 | Not specified | COMPLETED | The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery. |
| NCT04106947 | Not specified | UNKNOWN | Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations |
| NCT04149093 | Not specified | UNKNOWN | The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease |
| NCT04150120 | Not specified | COMPLETED | eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness |
| NCT04213976 | Not specified | UNKNOWN | Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis |
| NCT04476225 | Not specified | COMPLETED | Induced Pluripotent Stem Cells for Disease Research |
| NCT04598841 | Not specified | COMPLETED | Nutrition Support for Hirschsprung Disease |
| NCT04622410 | Not specified | RECRUITING | Registry for Hirschsprung Disease of the BELAPS |
| NCT04624334 | Not specified | TERMINATED | Non-invasive Assessment of Colonic Motility |
| NCT04730128 | Not specified | COMPLETED | Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients |
| NCT04837963 | Not specified | COMPLETED | Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children |
| NCT04957667 | Not specified | COMPLETED | Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population |
| NCT05038345 | Not specified | TERMINATED | Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample |
| NCT05044741 | Not specified | COMPLETED | Risk Factors of Perforated HSCR in Neonates |
| NCT05293353 | Not specified | UNKNOWN | Neokare Safety and Tolerability Assessment in Neonates With GI Problems |
| NCT05307419 | Not specified | UNKNOWN | Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease |
| NCT05450991 | Not specified | RECRUITING | Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations |
| NCT05655845 | Not specified | UNKNOWN | Risk Factors for Bowel Dysfunction at Preschool and Early Childhood Age in Children With Hirschsprung Disease |
| NCT06072976 | Not specified | RECRUITING | The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies |
| NCT06197061 | Not specified | UNKNOWN | Comparison of Robot-assisted With Laparoscopic-assisted Modified Soave Procedure for Classical Hirschsprung Disease |
| NCT06573723 | Not specified | RECRUITING | Institutional Registry of Rare Diseases |
| NCT06590142 | Not specified | RECRUITING | Hirschsprung’s Advances; Working Towards Autologous tIssue therapIes |
| NCT06592534 | Not specified | NOT_YET_RECRUITING | Babies With Enterocolitis - A Study of Faecal Calprotectin in Hirschsprung Disease (The BEACH Study) |
| NCT06650683 | Not specified | RECRUITING | Impact of Providing Nursing Support on Parental Stress Related to Preoperative Care of a Newborn with Hirschsprung’s Disease |
Related Atlas pages
- Associated diseases: asthma-related traits, susceptibility to, 5
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): asthma-related traits, susceptibility to, 5, Hirschsprung disease, susceptibility to, 1, smooth surface dental caries