IRAK3

interleukin 1 receptor associated kinase 3, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 12:66189194-66254622

Links

ENSG00000090376 ∙ NCBI:11213 ∙ OMIM:604459 ∙ HGNC:17020 ∙ Uniprot:Q9Y616 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• asthma-related traits, susceptibility to, 5 (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRAK3 gene.

• Inborn genetic diseases (21 variants)
• not provided (13 variants)
• Multisystem inflammatory syndrome in children (1 variants)
• Hirschsprung disease, susceptibility to, 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRAK3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			21	1		22
nonsense		1	2	1		4
start loss				1		1
frameshift		1		1		2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	2	23	5	1

Variants in IRAK3

This is a list of pathogenic ClinVar variants found in the IRAK3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-66189300-A-G			Likely benign (Mar 30, 2018)
12-66189304-C-A			Uncertain significance (Oct 12, 2017)
12-66189304-C-G		not specified	Uncertain significance (Jan 23, 2024)
12-66189324-G-A		not specified	Uncertain significance (Jan 24, 2023)
12-66189343-C-A		not specified	Uncertain significance (Aug 08, 2022)
12-66189393-C-A			Uncertain significance (Dec 05, 2019)
12-66189396-G-A		not specified	Uncertain significance (Dec 11, 2023)
12-66203730-C-G		not specified	Uncertain significance (May 26, 2022)
12-66203767-C-G		not specified	Uncertain significance (Jan 17, 2024)
12-66203782-A-G		not specified	Uncertain significance (Feb 21, 2024)
12-66203803-T-C		not specified	Uncertain significance (Jun 23, 2021)
12-66203804-G-A		Asthma-related traits, susceptibility to, 5	risk factor (Jun 01, 2007)
12-66203860-C-T		not specified	Uncertain significance (May 02, 2023)
12-66203861-A-G		not specified	Uncertain significance (Feb 27, 2023)
12-66203872-A-G		not specified	Uncertain significance (Jun 06, 2023)
12-66203884-A-C		not specified	Uncertain significance (Dec 19, 2023)
12-66203885-C-T		not specified	Uncertain significance (Dec 20, 2023)
12-66209521-G-T		Asthma-related traits, susceptibility to, 5	risk factor (Jun 01, 2007)
12-66209530-G-A		IRAK3-related disorder	Likely benign (Sep 09, 2019)
12-66210153-G-T		not specified	Uncertain significance (Jan 08, 2024)
12-66210189-C-T		not specified	Uncertain significance (May 26, 2023)
12-66210200-A-G			Benign (Dec 31, 2019)
12-66211448-A-G		IRAK3-related disorder	Benign (Oct 17, 2019)
12-66211452-T-A		not specified	Uncertain significance (Jun 29, 2023)
12-66211477-A-G		IRAK3-related disorder	Benign (Jan 03, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRAK3	protein_coding	protein_coding	ENST00000261233	12	65744

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.31e-21	0.000403	125383	1	364	125748	0.00145

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0745	315	311	1.01	0.0000153	3929
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00588	0.00588
Ashkenazi Jewish	0.00	0.00
East Asian	0.00169	0.00169
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000793	0.000791
Middle Eastern	0.00169	0.00169
South Asian	0.00101	0.00101
Other	0.00163	0.00163

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Neurotrophin signaling pathway - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;IL-1 signaling pathway;Signaling by Interleukins;signal transduction through il1r;Cytokine Signaling in Immune system;Toll-Like Receptors Cascades;Interleukin-1 signaling;Innate Immune System;Immune System;IL1;Toll Like Receptor 4 (TLR4) Cascade;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;IL1-mediated signaling events;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.209

Intolerance Scores

• loftool: 0.982
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.54

Haploinsufficiency Scores

• pHI: 0.127
• hipred: N
• hipred_score: 0.394
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.941

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Irak3
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; hematopoietic system phenotype; endocrine/exocrine gland phenotype; limbs/digits/tail phenotype; immune system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: irak3
• Affected structure: blood cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• 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;negative regulation of macrophage cytokine production;cytokine-mediated signaling pathway;negative regulation of NF-kappaB transcription factor activity;response to peptidoglycan;response to lipopolysaccharide;negative regulation of interleukin-12 production;negative regulation of interleukin-6 production;negative regulation of tumor necrosis factor production;negative regulation of toll-like receptor signaling pathway;intracellular signal transduction;negative regulation of protein catabolic process;negative regulation of protein complex disassembly;regulation of protein complex disassembly;response to exogenous dsRNA;negative regulation of MAP kinase activity;negative regulation of innate immune response;protein autophosphorylation;positive regulation of NF-kappaB transcription factor activity;interleukin-1-mediated signaling pathway;response to interleukin-1
• Cellular component: nucleus;cytoplasm;plasma membrane
• Molecular function: magnesium ion binding;protein serine/threonine kinase activity;ATP binding;protein homodimerization activity;protein heterodimerization activity