IRAK2

interleukin 1 receptor associated kinase 2

Basic information

Region (hg38): 3:10164918-10243745

Links

ENSG00000134070 ∙ NCBI:3656 ∙ OMIM:603304 ∙ HGNC:6113 ∙ Uniprot:O43187 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRAK2 gene.

• Inborn genetic diseases (28 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRAK2 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				2		2
missense			27	1	1	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	27	4	1

Variants in IRAK2

This is a list of pathogenic ClinVar variants found in the IRAK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-10164953-C-T			Likely benign (Mar 01, 2023)
3-10164967-A-G		not specified	Uncertain significance (Sep 14, 2022)
3-10164971-A-G		not specified	Uncertain significance (Feb 21, 2024)
3-10177875-G-T		not specified	Uncertain significance (Aug 21, 2023)
3-10177915-C-T		not specified	Uncertain significance (May 22, 2023)
3-10177916-G-A		not specified	Uncertain significance (Jun 28, 2022)
3-10177978-T-A		not specified	Uncertain significance (Jul 05, 2023)
3-10178004-C-T			Likely benign (Mar 01, 2023)
3-10200402-C-G		not specified	Uncertain significance (Dec 15, 2023)
3-10200479-G-A		not specified	Uncertain significance (Feb 07, 2023)
3-10209613-A-G		not specified	Uncertain significance (May 03, 2023)
3-10209618-G-A		not specified	Uncertain significance (Oct 17, 2023)
3-10209666-G-A		not specified	Likely benign (Jul 20, 2022)
3-10213252-G-A		not specified	Uncertain significance (Nov 30, 2021)
3-10213284-C-T			Likely benign (Feb 01, 2023)
3-10213358-G-T		not specified	Uncertain significance (Jun 06, 2023)
3-10213485-C-G		not specified	Uncertain significance (Sep 06, 2022)
3-10213511-G-A		not specified	Uncertain significance (Apr 22, 2022)
3-10213541-T-C		not specified	Uncertain significance (Jan 26, 2022)
3-10216948-A-G		not specified	Uncertain significance (Jan 23, 2024)
3-10216950-G-T		not specified	Uncertain significance (Jun 17, 2022)
3-10219687-C-T		not specified	Uncertain significance (Oct 03, 2022)
3-10219693-C-G		not specified	Uncertain significance (Mar 27, 2023)
3-10219770-A-T		not specified	Uncertain significance (Mar 30, 2022)
3-10222648-G-T		not specified	Uncertain significance (Apr 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRAK2	protein_coding	protein_coding	ENST00000256458	13	78879

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.61e-19	0.00768	125522	1	225	125748	0.000899

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0632	374	371	1.01	0.0000216	4056
Missense in Polyphen		122	124.01	0.98378		1325
Synonymous	0.716	141	152	0.926	0.00000973	1246
Loss of Function	0.396	30	32.4	0.925	0.00000160	352

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00220	0.00220
Ashkenazi Jewish	0.00	0.00
East Asian	0.00136	0.00136
Finnish	0.0000937	0.0000924
European (Non-Finnish)	0.000995	0.000950
Middle Eastern	0.00136	0.00136
South Asian	0.000593	0.000588
Other	0.00102	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization. {ECO:0000269|PubMed:10383454, ECO:0000269|PubMed:9374458}.
• Pathway: Neurotrophin signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);JAK-STAT-Ncore;Regulation of toll-like receptor signaling pathway;IL-1 signaling pathway;Structural Pathway of Interleukin 1 (IL-1);Fibrin Complement Receptor 3 Signaling Pathway;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signaling by Interleukins;signal transduction through il1r;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Interleukin-1 signaling;Innate Immune System;Immune System;IL1;IL-7 signaling;IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1;activated TAK1 mediates p38 MAPK activation;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;MyD88 dependent cascade initiated on endosome;JAK STAT pathway and regulation;EPO signaling;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;VEGF;IRAK2 mediated activation of TAK1 complex;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;Endogenous TLR signaling;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.528
• rvis_EVS: 1.23
• rvis_percentile_EVS: 93.26

Haploinsufficiency Scores

• pHI: 0.0823
• hipred: N
• hipred_score: 0.477

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irak2
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Gene ontology

• Biological process: activation of MAPK activity;regulation of cytokine-mediated signaling pathway;toll-like receptor signaling pathway;MyD88-dependent toll-like receptor signaling pathway;protein phosphorylation;inflammatory response;I-kappaB kinase/NF-kappaB signaling;JNK cascade;cytokine-mediated signaling pathway;lipopolysaccharide-mediated signaling pathway;negative regulation of NF-kappaB transcription factor activity;toll-like receptor 9 signaling pathway;intracellular signal transduction;positive regulation of NF-kappaB transcription factor activity;nucleotide-binding oligomerization domain containing signaling pathway;interleukin-1-mediated signaling pathway;response to interleukin-1
• Cellular component: nucleus;cytoplasm;cytosol;plasma membrane;endosome membrane
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;protein homodimerization activity;protein heterodimerization activity