Irak4 Deficiency

Categories: Genetic diseases, Rare diseases, Blood diseases, Immune diseases

Aliases & Classifications for Irak4 Deficiency

MalaCards integrated aliases for Irak4 Deficiency:

Name: Irak4 Deficiency 54 50 24 25 56 71 29 13 69
Interleukin-1 Receptor-Associated Kinase 4 Deficiency 25 69
Irak-4 Deficiency 50 25
Irak4d 24 71
Immunodeficiency Due to Interleukin-1 Receptor-Associated Kinase-4 Deficiency 56
Interleukin Receptor-Associated Kinase Deficiency 50
Interleukin 1 Receptor-Associated Kinase 4 13


Orphanet epidemiological data:

immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: any age;


Orphanet: 56  
Rare immunological diseases

External Ids:

OMIM 54 607676
Orphanet 56 ORPHA70592
UMLS via Orphanet 70 C1843256
ICD10 via Orphanet 34 D84.8
MedGen 40 C1843256
SNOMED-CT via HPO 65 165517008 234532001

Summaries for Irak4 Deficiency

NIH Rare Diseases : 50 irak-4 deficiency is a condition that affects the immune system (primary immunodeficiency). it causes recurring severe infections by a type of bacteria called pyogenic bacteria. individuals with irak-4 deficiency seem to be particularly susceptible to infections caused by bacteria called streptococcus pneumoniae. the deficiency is caused by mutations in the irak4 gene and is inherited in an autosomal recessive pattern. treatment may include intravenous immunoglobulin therapy (ivig), taking antibiotics before an infection develops, and vaccines. althought the infections can be life-threatening, they tend to occur less often as a person gets older. last updated: 9/20/2013

MalaCards based summary : Irak4 Deficiency, also known as interleukin-1 receptor-associated kinase 4 deficiency, is related to leukocyte adhesion deficiency, type iii and prothrombin thrombophilia, and has symptoms including neutropenia, immunodeficiency and recurrent streptococcus pneumoniae infections. An important gene associated with Irak4 Deficiency is IRAK4 (Interleukin 1 Receptor Associated Kinase 4), and among its related pathways/superpathways are Innate Immune System and HIV Life Cycle. Related phenotypes are hematopoietic system and adipose tissue

Genetics Home Reference : 25 IRAK-4 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This immunodeficiency leads to recurrent infections by a subset of bacteria known as pyogenic bacteria but not by other infectious agents. (Infection with pyogenic bacteria causes the production of pus.) The most common infections in IRAK-4 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent with age.

OMIM : 54
IRAK4 deficiency is an autosomal recessive primary immunodeficiency that impairs Toll (see TLR4; 603030)/IL1R (see IL1R1; 147810) immunity, except for the TLR3 (603029)- and TLR4-interferon-alpha (IFNA; 147660)/beta (IFNB; 147640) pathways (Ku et al., 2007). (607676)

UniProtKB/Swiss-Prot : 71 IRAK4 deficiency: Causes extracellular pyogenic bacterial and fungal infections in otherwise healthy children.

Related Diseases for Irak4 Deficiency

Diseases related to Irak4 Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
id Related Disease Score Top Affiliating Genes
1 leukocyte adhesion deficiency, type iii 10.9
2 prothrombin thrombophilia 10.6 TLR2 TLR4
3 fibrosis of extraocular muscles, congenital, 1 10.6 IRAK4 TIRAP
4 rickettsialpox 10.6 TLR2 TLR4
5 oculo-cerebral dysplasia 10.5 TLR1 TLR5
6 antigen-peptide-transporter 2 deficiency 10.5 TLR2 TLR4
7 fanconi syndrome 10.5 TLR2 TLR4
8 arteriosclerosis 10.5 BTK MYD88
9 mycobacterium kansasii 10.5 TLR1 TLR2
10 aseptic meningitis 10.4 TLR2 TLR4
11 queensland tick typhus 10.4 MYD88 TLR2
12 alkhurma hemorrhagic fever 10.4 TLR2 TLR4
13 hereditary choroidal atrophy 10.4 MYD88 TLR2 TLR4
14 neonatal meningitis 10.4 TLR2 TLR4
15 hypertensive heart disease 10.3 TLR2 TLR4 TLR5
16 mixed malaria 10.3 IRAK4 MYD88
17 gastroduodenal crohn's disease 10.3 TLR2 TLR4 TLR5
18 mycobacterium malmoense 10.3 CD14 TLR2
19 adenoid squamous cell carcinoma 10.3 TLR2 TLR4 TLR5
20 mycobacterium xenopi 10.2 CD14 TLR2
21 lateral cystocele 10.2 TIRAP TLR1 TLR4
22 thymus clear cell carcinoma 10.1 TLR2 TLR4
23 epidermolysis bullosa dystrophica, ad 10.1 TIRAP TLR2
24 nasopharyngitis 10.1 MYD88 TLR2 TLR4 TLR5
25 inner ear disease 10.0 TLR1 TLR10 TLR4
26 asphyxiating thoracic dystrophy 10.0 TLR2 TLR4 TLR5
27 pellagra 10.0 TLR4 TLR6
28 megaloblastic anemia 9.9 TLR2 TLR4
29 pericarditis 9.9
30 pleural empyema 9.9
31 common cold 9.8 TLR4 TLR5 TLR6
32 pneumonia 9.8
33 hyper ige syndrome 9.8
34 bartonellosis 9.8 TLR1 TLR10 TLR2 TLR4
35 neutrophil-specific granule deficiency 9.8 TLR1 TLR2 TLR6
36 uterine adnexa cancer 9.7 TLR1 TLR2 TLR6
37 trichosporonosis 9.5 TLR1 TLR2 TLR4 TLR6
38 tinea barbae 9.5 TLR1 TLR2 TLR4 TLR6
39 gastric ulcer 9.5 TLR1 TLR2 TLR4 TLR6
40 malaria 9.4 CD36 MYD88 TIRAP TLR2 TLR4
41 compensatory emphysema 9.1 TIRAP TLR1 TLR2 TLR4 TLR6
42 melioidosis 9.0 LY96 TLR1 TLR10 TLR2 TLR4 TLR5
43 schneiderian carcinoma 8.8 MYD88 TIRAP TLR1 TLR2 TLR4 TLR6
44 anal atresia, hypospadias, and penoscrotal inversion 6.3 BTK CD14 CD36 IRAK4 LY96 MYD88
45 invasive pneumococcal disease, recurrent isolated, 1 5.7 BTK CD14 CD36 IRAK4 LY96 MYD88

Graphical network of the top 20 diseases related to Irak4 Deficiency:

Diseases related to Irak4 Deficiency

Symptoms & Phenotypes for Irak4 Deficiency

Clinical features from OMIM:


Human phenotypes related to Irak4 Deficiency:

56 32
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 neutropenia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001875
2 immunodeficiency 56 32 hallmark (90%) Very frequent (99-80%) HP:0002721
3 recurrent streptococcus pneumoniae infections 56 32 hallmark (90%) Very frequent (99-80%) HP:0005366
4 recurrent staphylococcal infections 56 32 hallmark (90%) Very frequent (99-80%) HP:0007499
5 recurrent bacterial infections 56 Very frequent (99-80%)

MGI Mouse Phenotypes related to Irak4 Deficiency:

id Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.93 BTK CD14 CD36 IRAK4 LY96 MYD88
2 adipose tissue MP:0005375 9.8 CD14 CD36 MYD88 TLR2 TLR4 TLR5
3 digestive/alimentary MP:0005381 9.73 BTK CD36 MYD88 TLR2 TLR4 TLR5
4 homeostasis/metabolism MP:0005376 9.61 TLR2 TLR4 TLR5 BTK CD14 CD36
5 immune system MP:0005387 9.4 CD14 CD36 IRAK4 LY96 MYD88 TIRAP

Drugs & Therapeutics for Irak4 Deficiency

Search Clinical Trials , NIH Clinical Center for Irak4 Deficiency

Genetic Tests for Irak4 Deficiency

Genetic tests related to Irak4 Deficiency:

id Genetic test Affiliating Genes
1 Irak4 Deficiency 29 24 IRAK4

Anatomical Context for Irak4 Deficiency

Publications for Irak4 Deficiency

Articles related to Irak4 Deficiency:

id Title Authors Year
IRAK4 Deficiency in a Patient with Recurrent Pneumococcal Infections: Case Report and Review of the Literature. ( 28503543 )
IRAK4 deficiency promotes cardiac remodeling induced by pressure overload. ( 26884959 )
Recurrent systemic pneumococcal disease and IRAK4 deficiency. ( 17984826 )

Variations for Irak4 Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Irak4 Deficiency:

id Symbol AA change Variation ID SNP ID
1 IRAK4 p.Arg12Cys VAR_072888 rs377584435
2 IRAK4 p.Gly298Asp VAR_072892 rs568782766

ClinVar genetic disease variations for Irak4 Deficiency:

id Gene Variation Type Significance SNP ID Assembly Location
1 IRAK4 IRAK4, 1-BP DEL, 821T deletion Pathogenic
2 IRAK4 NM_016123.3(IRAK4): c.877C> T (p.Gln293Ter) single nucleotide variant Pathogenic rs121908002 GRCh37 Chromosome 12, 44172041: 44172041
3 IRAK4 IRAK4, 2-BP DEL, 620AC deletion Pathogenic
4 IRAK4 IRAK4, IVS7DS, G-T, +5 single nucleotide variant Pathogenic
5 IRAK4 NM_016123.3(IRAK4): c.34C> T (p.Arg12Cys) single nucleotide variant Pathogenic/Likely pathogenic rs377584435 GRCh37 Chromosome 12, 44161948: 44161948

Expression for Irak4 Deficiency

Search GEO for disease gene expression data for Irak4 Deficiency.

Pathways for Irak4 Deficiency

Pathways related to Irak4 Deficiency according to GeneCards Suite gene sharing:

(show all 43)
id Super pathways Score Top Affiliating Genes
Show member pathways
13.99 BTK CD14 CD36 IRAK4 LY96 MYD88
Show member pathways
13.64 BTK CD14 CD36 IRAK4 LY96 MYD88
Show member pathways
13.49 BTK CD14 CD36 LY96 MYD88 TIRAP
Show member pathways
13.46 BTK CD14 CD36 IRAK4 LY96 MYD88
Show member pathways
Show member pathways
13.24 BTK CD14 IRAK4 MYD88 TLR1 TLR10
Show member pathways
12.97 BTK CD14 CD36 IRAK4 LY96 MYD88
Show member pathways
12.76 IRAK4 MYD88 TLR1 TLR10 TLR2 TLR4
Show member pathways
12.68 IRAK4 MYD88 TLR2 TLR4
Show member pathways
11 12.61 BTK IRAK4 MYD88 TLR1 TLR2 TLR6
Show member pathways
Show member pathways
12.52 CD14 IRAK4 LY96 MYD88 TIRAP TLR4
Show member pathways
12.48 CD14 LY96 TLR4 TLR5
Show member pathways
12.38 CD14 IRAK4 LY96 MYD88 TIRAP TLR4
Show member pathways
12.32 IRAK4 LY96 MYD88 TLR2 TLR4
17 12.3 TLR1 TLR10 TLR2 TLR4 TLR5 TLR6
Show member pathways
12.28 BTK CD14 LY96 TLR4
19 12.26 CD14 IRAK4 MYD88 TIRAP TLR1 TLR2
20 12.22 CD14 CD36 TLR2 TLR4 TLR6
21 12.18 TLR1 TLR10 TLR2 TLR4 TLR5 TLR6
Show member pathways
12.14 TLR1 TLR10 TLR2 TLR4 TLR5 TLR6
Show member pathways
12.1 BTK CD14 CD36 LY96 MYD88 TIRAP
Show member pathways
12.05 TLR1 TLR10 TLR2 TLR4 TLR5 TLR6
Show member pathways
12.01 TLR1 TLR10 TLR2 TLR4 TLR5 TLR6
26 11.95 BTK CD14 IRAK4 LY96 MYD88 TIRAP
Show member pathways
11.94 CD14 LY96 MYD88 TLR4
28 11.92 TLR1 TLR10 TLR2 TLR4 TLR5 TLR6
29 11.9 CD14 MYD88 TLR4 TLR5
30 11.85 CD14 IRAK4 LY96 MYD88 TIRAP TLR4
31 11.84 CD14 TLR2 TLR4
32 11.81 BTK CD14 IRAK4 LY96 MYD88 TLR4
33 11.8 CD36 TLR2 TLR4 TLR5
34 11.73 CD14 MYD88 TLR2 TLR4 TLR5
35 11.68 CD14 LY96 MYD88 TLR4
36 11.67 IRAK4 MYD88 TIRAP
37 11.63 CD36 MYD88 TLR2 TLR4
Show member pathways
11.54 CD14 IRAK4 LY96 MYD88 TIRAP TLR1
39 11.47 CD14 CD36 LY96 TLR4
40 11.25 MYD88 TLR1 TLR2
41 11.23 CD14 LY96 TLR4
42 11.01 MYD88 TLR2
43 10.91 CD14 LY96 TLR4

GO Terms for Irak4 Deficiency

Cellular components related to Irak4 Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.91 CD36 TLR1 TLR10 TLR2 TLR4 TLR6
2 endosome membrane GO:0010008 9.65 CD14 IRAK4 LY96 MYD88 TLR4
3 phagocytic vesicle membrane GO:0030670 9.58 TLR1 TLR2 TLR6
4 intrinsic component of plasma membrane GO:0031226 9.54 LY96 TLR2 TLR4
5 plasma membrane GO:0005886 9.44 BTK CD14 CD36 IRAK4 LY96 MYD88
6 membrane raft GO:0045121 9.43 BTK CD14 CD36 TLR1 TLR2 TLR6
7 lipopolysaccharide receptor complex GO:0046696 9.33 CD14 LY96 TLR4
8 Toll-like receptor 1-Toll-like receptor 2 protein complex GO:0035354 9.32 TLR1 TLR2

Biological processes related to Irak4 Deficiency according to GeneCards Suite gene sharing:

(show top 50) (show all 69)
id Name GO ID Score Top Affiliating Genes
1 defense response to Gram-positive bacterium GO:0050830 9.98 CD36 MYD88 TIRAP TLR2
2 apoptotic signaling pathway GO:0097190 9.95 BTK CD14 LY96 TLR4
3 I-kappaB kinase/NF-kappaB signaling GO:0007249 9.94 BTK CD14 LY96 TLR4
4 positive regulation of interleukin-6 production GO:0032755 9.94 CD36 MYD88 TLR2 TLR4
5 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.92 CD36 TIRAP TLR4
6 lipopolysaccharide-mediated signaling pathway GO:0031663 9.91 CD14 LY96 MYD88 TLR2 TLR4
7 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.91 BTK IRAK4 MYD88 TIRAP TLR2 TLR4
8 positive regulation of tumor necrosis factor production GO:0032760 9.91 CD14 CD36 LY96 MYD88 TIRAP TLR2
9 immune system process GO:0002376 9.9 BTK CD14 IRAK4 LY96 MYD88 TLR1
10 cellular response to mechanical stimulus GO:0071260 9.89 MYD88 TLR4 TLR5
11 positive regulation of JNK cascade GO:0046330 9.89 MYD88 TIRAP TLR4
12 positive regulation of interleukin-8 production GO:0032757 9.89 TIRAP TLR2 TLR4 TLR5
13 positive regulation of inflammatory response GO:0050729 9.88 TLR10 TLR2 TLR4
14 positive regulation of interleukin-12 production GO:0032735 9.88 CD36 TIRAP TLR2 TLR4
15 cellular response to lipoteichoic acid GO:0071223 9.85 CD14 CD36 TIRAP TLR2 TLR4
16 necroptotic process GO:0070266 9.84 CD14 LY96 TLR4
17 negative regulation of growth of symbiont in host GO:0044130 9.84 CD36 MYD88 TIRAP
18 cell activation GO:0001775 9.83 TLR1 TLR2 TLR6
19 toll-like receptor 4 signaling pathway GO:0034142 9.83 CD14 LY96 TIRAP TLR4
20 MyD88-independent toll-like receptor signaling pathway GO:0002756 9.82 CD14 LY96 TLR4
21 interleukin-1 beta secretion GO:0050702 9.81 CD36 TLR4 TLR6
22 positive regulation of interleukin-6 biosynthetic process GO:0045410 9.8 TIRAP TLR1 TLR6
23 toll-like receptor TLR6:TLR2 signaling pathway GO:0038124 9.8 CD14 CD36 TLR2 TLR6
24 negative regulation of MyD88-independent toll-like receptor signaling pathway GO:0034128 9.79 CD14 LY96 TLR4
25 positive regulation of NLRP3 inflammasome complex assembly GO:1900227 9.78 CD36 TLR4 TLR6
26 cellular response to diacyl bacterial lipopeptide GO:0071726 9.78 CD14 CD36 TLR2 TLR6
27 TRIF-dependent toll-like receptor signaling pathway GO:0035666 9.77 CD14 LY96 TLR4
28 cellular response to bacterial lipopeptide GO:0071221 9.75 CD36 TIRAP TLR2
29 positive regulation of interferon-beta production GO:0032728 9.74 TLR2 TLR4
30 positive regulation of interleukin-10 production GO:0032733 9.74 TLR2 TLR4
31 positive regulation of NF-kappaB import into nucleus GO:0042346 9.74 TLR2 TLR4
32 response to fatty acid GO:0070542 9.74 CD36 TLR2
33 cellular response to triacyl bacterial lipopeptide GO:0071727 9.74 CD14 TLR1 TLR2
34 3-UTR-mediated mRNA stabilization GO:0070935 9.73 MYD88 TIRAP
35 activation of NF-kappaB-inducing kinase activity GO:0007250 9.73 TIRAP TLR6
36 positive regulation of chemokine production GO:0032722 9.73 TLR2 TLR4
37 toll-like receptor 9 signaling pathway GO:0034162 9.73 IRAK4 MYD88
38 microglial cell activation GO:0001774 9.73 TLR2 TLR6
39 positive regulation of nitric-oxide synthase biosynthetic process GO:0051770 9.73 TLR2 TLR4
40 toll-like receptor TLR1:TLR2 signaling pathway GO:0038123 9.73 CD14 TLR1 TLR2
41 response to molecule of bacterial origin GO:0002237 9.72 CD14 TLR2
42 I-kappaB phosphorylation GO:0007252 9.72 TLR2 TLR4
43 T-helper 1 type immune response GO:0042088 9.72 TLR4 TLR6
44 positive regulation of tumor necrosis factor biosynthetic process GO:0042535 9.72 TLR1 TLR4
45 macrophage activation GO:0042116 9.72 TLR1 TLR4
46 positive regulation of lymphocyte proliferation GO:0050671 9.71 MYD88 TLR4
47 positive regulation of macrophage cytokine production GO:0060907 9.71 CD36 TLR4
48 detection of lipopolysaccharide GO:0032497 9.7 LY96 TLR4
49 positive regulation of toll-like receptor signaling pathway GO:0034123 9.7 TLR2 TLR5
50 nitric oxide metabolic process GO:0046209 9.69 TLR2 TLR6

Molecular functions related to Irak4 Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 receptor activity GO:0004872 9.76 TLR1 TLR2 TLR4 TLR6
2 transmembrane signaling receptor activity GO:0004888 9.72 TLR1 TLR10 TLR4 TLR5 TLR6
3 protein heterodimerization activity GO:0046982 9.61 TIRAP TLR1 TLR2
4 lipopolysaccharide binding GO:0001530 9.54 CD14 TLR2 TLR4
5 receptor binding GO:0005102 9.48 BTK MYD88
6 interleukin-1 receptor binding GO:0005149 9.43 IRAK4 MYD88 TLR5
7 lipopolysaccharide receptor activity GO:0001875 9.33 LY96 TLR2 TLR4
8 Toll-like receptor 2 binding GO:0035663 9.13 TIRAP TLR1 TLR6
9 Toll-like receptor binding GO:0035325 9.1 TLR2
10 lipopeptide binding GO:0071723 8.92 CD14 TLR1 TLR2 TLR6

Sources for Irak4 Deficiency

9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
32 HPO
33 ICD10
34 ICD10 via Orphanet
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
52 Novoseek
55 OMIM via Orphanet
59 PubMed
66 SNOMED-CT via Orphanet
68 Tocris
70 UMLS via Orphanet
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