IRAK2

protein-coding

interleukin 1 receptor associated kinase 2

Gene summary

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]

MANE transcript

NM_001570.4

Inheritance

AR, AD

ClinVar variants

U:108B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr3:10,164,919-10,243,745

External References & Databases

Ensembl (ENSG00000134070)

Transcript & Mutation Effects

hg38 • Region Span ~78.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immune dysregulation, autoimmunity, and autoinflammationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957790

Submitter: PanelApp Australia

immune dysregulation, autoimmunity, and autoinflammationLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0957790

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IRAK2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 100

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001570.4. 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 clinvar	2 clinvar		4
missense			103 clinvar	6 clinvar		109
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	108	8	0	116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001570.4	RefSeq	NP_001561.3	13	MANE Select
ENST00000256458.5	Ensembl	ENSP00000256458.4	13	MANE Select
ENST00000873196.1	Ensembl	ENSP00000543255.1	12	Standard
ENST00000873196.2	Ensembl	ENSP00000543255.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neurotrophin signaling pathway - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)
JAK-STAT-Ncore
Regulation of toll-like receptor signaling pathway
IL-1 signaling pathway

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

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding
protein homodimerization activity
protein heterodimerization activity

Cellular Component

nucleus
cytoplasm
cytosol
plasma membrane
endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256458
Coding exons: 13
Length: 78879
Individuals with no LoFs: 125522
Homozygous LoFs: 1
Heterozygous LoFs: 225
Defined: 125748
p: 0.000899

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0632	374	371	1.01	0.0000216	4056
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.0018	0.0017	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0014	0.0014	notable
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.0010	0.00095	rare
South Asian	0.00059	0.00059	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.177

Intolerance Scores

LoFtool: 0.528
RVIS EVS: 1.23
RVIS percentile EVS: 93.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

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