IRAK3
protein-codinginterleukin 1 receptor associated kinase 3, the group of MicroRNA protein coding host genes
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~65.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0012607
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IRAK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007199.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 4 | 3 | 9 | ||
| missense | 90 | 6 | 2 | 98 | ||
| nonsense | 1 | 5 | 1 | 7 | ||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 2 | 1 | 4 | ||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 2 | 104 | 13 | 5 | 124 |
Highest pathogenic variant AF is 0.00001163241
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009130.2 | 12 | MANE Select | |
| Ensembl | ENSP00000261233.4 | 12 | MANE Select | |
| RefSeq | NP_001135995.1 | 11 | Standard | |
| Ensembl | ENSP00000409852.2 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| irak3 | Danio rerio | Structure: blood cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neurotrophin signaling pathway - Homo sapiens (human)
- Regulation of toll-like receptor signaling pathway
- IL-1 signaling pathway
- Signaling by Interleukins
- signal transduction through il1r
Biological Process
- negative regulation of cytokine-mediated signaling pathway
- MyD88-dependent toll-like receptor signaling pathway
- protein phosphorylation
- response to virus
- positive regulation of macrophage tolerance induction
Molecular Function
- magnesium ion binding
- protein serine/threonine kinase activity
- ATP binding
- protein homodimerization activity
- protein heterodimerization activity
Cellular Component
- nucleus
- cytoplasm
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261233
- Coding exons
- 12
- Length
- 65744
- Individuals with no LoFs
- 125383
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 364
- Defined
- 125748
- p
- 0.00145
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0745 | 315 | 311 | 1.01 | 0.0000153 | 3929 |
| Missense (PolyPhen) | 89 | 101.7 | 0.87511 | 1329 | ||
| Synonymous | 0.637 | 104 | 113 | 0.924 | 0.00000553 | 1089 |
| Loss of Function | -0.643 | 29 | 25.5 | 1.14 | 0.00000122 | 333 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.0058 | 0.0058 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0017 | 0.0017 | notable |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00079 | 0.00079 | rare |
| South Asian | 0.0010 | 0.0010 | notable |
| Other | 0.0016 | 0.0016 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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. {ECO:0000250|UniProtKB:Q8K4B2, ECO:0000269|PubMed:10383454}.;
Recessive Scores
- pRec
- 0.209
Intolerance Scores
- LoFtool
- 0.982
- RVIS EVS
- -0.35
- RVIS percentile EVS
- 29.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.941
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |