Irak4 Deficiency malady

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

Aliases & Classifications for Irak4 Deficiency

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Aliases & Descriptions for Irak4 Deficiency:

Name: Irak4 Deficiency 52 48 24 25 54 70 27 12 68
Interleukin-1 Receptor-Associated Kinase 4 Deficiency 25 68
Irak-4 Deficiency 48 25
Irak4d 24 70
Immunodeficiency Due to Interleukin-1 Receptor-Associated Kinase-4 Deficiency 54
Interleukin Receptor-Associated Kinase Deficiency 48
Interleukin 1 Receptor-Associated Kinase 4 12


Orphanet epidemiological data:

irak4 deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: any age


External Ids:

OMIM52 607676
Orphanet54 ORPHA70592
ICD10 via Orphanet31 D84.8
MedGen37 C1843256

Summaries for Irak4 Deficiency

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NIH Rare Diseases:48 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 fibrosis of extraocular muscles, congenital, 1 and sinonasal undifferentiated carcinoma, and has symptoms including abnormality of neutrophils, abnormality of immune system physiology and abnormality of the lymphatic system. An important gene associated with Irak4 Deficiency is IRAK4 (Interleukin 1 Receptor Associated Kinase 4), and among its related pathways are NTHi-Induced Signaling and AGE/RAGE pathway. Affiliated tissues include neutrophil, and related mouse phenotypes are digestive/alimentary and adipose tissue.

UniProtKB/Swiss-Prot:70 IRAK4 deficiency: Causes extracellular pyogenic bacterial and fungal infections in otherwise healthy children.

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:52 IRAK4 deficiency is an autosomal recessive primary immunodeficiency that impairs Toll (see TLR4; 603030)/IL1R (see... (607676) more...

Related Diseases for Irak4 Deficiency

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

(show all 47)
idRelated DiseaseScoreTop Affiliating Genes
1fibrosis of extraocular muscles, congenital, 110.5IRAK4, TIRAP
2sinonasal undifferentiated carcinoma10.4TLR2, TLR4
3rickettsialpox10.4TLR2, TLR4
4atrial septal defect coronary sinus10.4TLR2, TLR4
5queensland tick typhus10.4MYD88, TLR2
6antigen-peptide-transporter 2 deficiency10.4TLR2, TLR4
7pernicious anemia10.3TLR2, TLR4
8mycobacterium fortuitum10.3TLR1, TLR2
9generalized atherosclerosis10.3BTK, MYD88
10toxocariasis10.3MYD88, TLR2, TLR4
11spondylohypoplasia, arthrogryposis and popliteal pterygium10.3TLR2, TLR4
12binocular vision disease10.3MYD88, TLR2, TLR4
13gastroduodenal crohn's disease10.3TLR2, TLR4, TLR5
14gallbladder lymphoma10.3TLR2, TLR4, TLR5
15plasmodium malariae malaria10.3IRAK4, MYD88
16uterine inversion10.3MYD88, TLR2, TLR4
17sheehan syndrome10.2IRAK4, TLR2, TLR4
18inner ear cancer10.2TLR2, TLR4
19atrial tachyarrhythmia with short pr interval10.2TIRAP, TLR2
20bartonellosis10.2TLR1, TLR2, TLR4
21mycobacterium gordonae10.2CD14, TLR2
22acute cholangitis10.2TLR2, TLR4
23mycobacterium xenopi10.2CD14, TLR2
24bacteremia10.2TIRAP, TLR2, TLR4
25paraneoplastic polyneuropathy10.1LY96, TLR2, TLR4
26accessory nerve disease10.1TLR2, TLR4
27nasopharyngitis10.1MYD88, TLR2, TLR4, TLR5
28choline deficiency disease9.9TLR4, TLR6
30pleural empyema9.9
31atopy9.9CD14, TLR2, TLR4
32askin's tumor9.8TIRAP, TLR2
33nevus mucinosis9.8TLR1, TLR2, TLR6
34trichosporonosis9.8TLR1, TLR2, TLR6
36hyper ige syndrome9.8
37tinea barbae9.8TLR1, TLR4, TLR6
38parametrium malignant neoplasm9.7TLR1, TLR2, TLR6
39abducens nerve neoplasm9.6TIRAP, TLR1, TLR2, TLR4, TLR5
40motion sickness9.6TLR10, TLR4, TLR6
41gastric ulcer9.5TLR1, TLR2, TLR4, TLR6
42malaria9.4CD36, MYD88, TIRAP, TLR2, TLR4
43compensatory emphysema9.2TIRAP, TLR1, TLR2, TLR4, TLR6
44melioidosis9.2LY96, TLR1, TLR10, TLR2, TLR4, TLR5
45ovary transitional cell carcinoma8.9MYD88, TIRAP, TLR1, TLR2, TLR4, TLR6
46anal atresia, hypospadias, and penoscrotal inversion6.8BTK, CD14, CD36, IRAK4, LY96, MYD88
47invasive pneumococcal disease, recurrent isolated, 16.3BTK, 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

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Clinical features from OMIM:


Human phenotypes related to Irak4 Deficiency:

 64 54 (show all 8)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of neutrophils64 hallmark (90%) HP:0001874
2 abnormality of immune system physiology64 hallmark (90%) HP:0010978
3 abnormality of the lymphatic system64 hallmark (90%) HP:0100763
4 immunodeficiency64 54 Very frequent (99-80%) HP:0002721
5 neutropenia54 Very frequent (99-80%)
6 recurrent bacterial infections54 Very frequent (99-80%)
7 recurrent streptococcus pneumoniae infections54 Very frequent (99-80%)
8 recurrent staphylococcal infections54 Very frequent (99-80%)

MGI Mouse Phenotypes related to Irak4 Deficiency according to GeneCards Suite gene sharing:

idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053819.2BTK, CD36, MYD88, TLR2, TLR4, TLR5
2MP:00053759.0CD14, CD36, MYD88, TLR2, TLR4, TLR5
3MP:00053767.9BTK, CD14, CD36, IRAK4, MYD88, TIRAP
4MP:00053976.3BTK, CD14, CD36, IRAK4, LY96, MYD88
5MP:00053875.5BTK, CD14, CD36, IRAK4, LY96, MYD88

Drugs & Therapeutics for Irak4 Deficiency

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Irak4 Deficiency

Genetic Tests for Irak4 Deficiency

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Genetic tests related to Irak4 Deficiency:

id Genetic test Affiliating Genes
1 Irak4 Deficiency27 24 IRAK4

Anatomical Context for Irak4 Deficiency

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MalaCards organs/tissues related to Irak4 Deficiency:


Publications for Irak4 Deficiency

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Articles related to Irak4 Deficiency:

IRAK4 deficiency promotes cardiac remodeling induced by pressure overload. (26884959)
Recurrent systemic pneumococcal disease and IRAK4 deficiency. (17984826)

Variations for Irak4 Deficiency

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

id Symbol AA change Variation ID SNP ID

Clinvar genetic disease variations for Irak4 Deficiency:

id Gene Variation Type Significance SNP ID Assembly Location
1IRAK4NM_016123.3(IRAK4): c.34C> T (p.Arg12Cys)SNVPathogenicrs377584435GRCh37Chr 12, 44161948: 44161948
2IRAK4IRAK4, IVS7DS, G-T, +5SNVPathogenicChr na, -1: -1
3IRAK4IRAK4, 1-BP DEL, 821TdeletionPathogenicChr na, -1: -1
4IRAK4NM_016123.3(IRAK4): c.877C> T (p.Gln293Ter)SNVPathogenicrs121908002GRCh37Chr 12, 44172041: 44172041
5IRAK4IRAK4, 2-BP DEL, 620ACdeletionPathogenicChr na, -1: -1

Expression for genes affiliated with Irak4 Deficiency

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Search GEO for disease gene expression data for Irak4 Deficiency.

Pathways for genes affiliated with Irak4 Deficiency

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

(show all 36)
idSuper pathwaysScoreTop Affiliating Genes
19.9MYD88, TLR2
Show member pathways
9.3IRAK4, MYD88, TLR2, TLR4
49.2CD14, TLR2, TLR4
59.1CD14, LY96, TLR4
69.1CD14, LY96, TLR4
79.1CD36, MYD88, TLR2, TLR4
89.0CD36, TLR2, TLR4, TLR5
Show member pathways
9.0CD14, MYD88, TLR4, TLR5
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8.9IRAK4, LY96, MYD88, TLR2, TLR4
118.8CD14, LY96, MYD88, TLR4
Show member pathways
8.8CD14, LY96, TLR4, TLR5
138.7CD14, MYD88, TLR2, TLR4, TLR5
148.6CD14, CD36, LY96, TLR4
158.2CD14, IRAK4, LY96, MYD88, TIRAP, TLR4
Show member pathways
8.2CD14, IRAK4, LY96, MYD88, TIRAP, TLR4
Show member pathways
8.2CD14, IRAK4, LY96, MYD88, TIRAP, TLR4
188.1BTK, IRAK4, MYD88, TLR1, TLR2, TLR6
197.9CD14, CD36, TLR2, TLR4, TLR6
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
217.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
227.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
267.8BTK, CD14, IRAK4, LY96, MYD88, TIRAP
Show member pathways
7.4IRAK4, MYD88, TLR1, TLR10, TLR2, TLR4
Show member pathways
7.3BTK, IRAK4, TLR1, TLR10, TLR2, TLR4
297.1CD14, IRAK4, MYD88, TIRAP, TLR1, TLR2
Show member pathways
Show member pathways
6.4CD14, IRAK4, LY96, MYD88, TIRAP, TLR1
Show member pathways
6.4CD14, IRAK4, LY96, MYD88, TIRAP, TLR1
Show member pathways
6.4BTK, CD14, IRAK4, MYD88, TLR1, TLR10
Show member pathways
5.5BTK, CD14, IRAK4, LY96, MYD88, TIRAP
Show member pathways
5.0BTK, CD14, CD36, IRAK4, LY96, MYD88
Show member pathways
5.0BTK, CD14, CD36, IRAK4, LY96, MYD88

GO Terms for genes affiliated with Irak4 Deficiency

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

idNameGO IDScoreTop Affiliating Genes
1intrinsic component of plasma membraneGO:003122610.2LY96, TLR2, TLR4
2lipopolysaccharide receptor complexGO:00466969.9CD14, LY96, TLR4
3Toll-like receptor 1-Toll-like receptor 2 protein complexGO:00353549.8TLR1, TLR2
4phagocytic vesicle membraneGO:00306709.8TLR1, TLR2, TLR6
5endosome membraneGO:00100089.4CD14, IRAK4, LY96, MYD88, TLR4
6Golgi apparatusGO:00057948.6CD14, CD36, TLR1, TLR2, TLR6
7membrane raftGO:00451218.3BTK, CD14, CD36, TLR1, TLR2, TLR6
8integral component of plasma membraneGO:00058878.1CD36, TLR1, TLR10, TLR2, TLR4, TLR5
9plasma membraneGO:00058864.9BTK, CD14, CD36, IRAK4, LY96, MYD88

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

(show top 50)    (show all 61)
idNameGO IDScoreTop Affiliating Genes
1I-kappaB phosphorylationGO:000725210.6TLR2, TLR4
2positive regulation of lymphocyte proliferationGO:005067110.6MYD88, TLR4
33-UTR-mediated mRNA stabilizationGO:007093510.6MYD88, TIRAP
4detection of triacyl bacterial lipopeptideGO:004249510.6TLR1, TLR2
5positive regulation of chemokine productionGO:003272210.6TLR2, TLR4
6macrophage activationGO:004211610.5TLR1, TLR4
7positive regulation of interferon-beta productionGO:003272810.5TLR2, TLR4
8positive regulation of interleukin-10 productionGO:003273310.5TLR2, TLR4
9positive regulation of NF-kappaB import into nucleusGO:004234610.5TLR2, TLR4
10positive regulation of toll-like receptor signaling pathwayGO:003412310.5TLR2, TLR5
11positive regulation of nitric-oxide synthase biosynthetic processGO:005177010.5TLR2, TLR4
12detection of lipopolysaccharideGO:003249710.5LY96, TLR4
13positive regulation of tumor necrosis factor biosynthetic processGO:004253510.5TLR1, TLR4
14toll-like receptor 9 signaling pathwayGO:003416210.4IRAK4, MYD88
15cellular response to mechanical stimulusGO:007126010.4MYD88, TLR4, TLR5
16positive regulation of macrophage cytokine productionGO:006090710.3CD36, TLR4
17response to fatty acidGO:007054210.3CD36, TLR2
18response to bacteriumGO:000961710.2CD14, TLR4
19positive regulation of JNK cascadeGO:004633010.2MYD88, TIRAP, TLR4
20detection of diacyl bacterial lipopeptideGO:004249610.1TLR2, TLR6
21nitric oxide metabolic processGO:004620910.0TLR2, TLR6
22positive regulation of inflammatory responseGO:005072910.0TLR10, TLR2, TLR4
23activation of NF-kappaB-inducing kinase activityGO:000725010.0TIRAP, TLR6
24negative regulation of growth of symbiont in hostGO:004413010.0CD36, MYD88, TIRAP
25cellular response to bacterial lipopeptideGO:007122110.0CD36, TIRAP, TLR2
26response to bacterial lipoproteinGO:003249310.0TLR2, TLR6
27cellular response to triacyl bacterial lipopeptideGO:007172710.0CD14, TLR1, TLR2
28positive regulation of ERK1 and ERK2 cascadeGO:00703749.9CD36, TIRAP, TLR4
29T-helper 1 type immune responseGO:00420889.9TLR4, TLR6
30positive regulation of interleukin-8 productionGO:00327579.8TIRAP, TLR2, TLR4, TLR5
31MyD88-independent toll-like receptor signaling pathwayGO:00027569.8CD14, LY96, TLR4
32necroptotic processGO:00702669.8CD14, LY96, TLR4
33negative regulation of MyD88-independent toll-like receptor signaling pathwayGO:00341289.8CD14, LY96, TLR4
34defense response to bacteriumGO:00427429.8TLR1, TLR4, TLR6
35positive regulation of interleukin-6 productionGO:00327559.7CD36, MYD88, TLR2, TLR4
36defense response to Gram-positive bacteriumGO:00508309.7CD36, MYD88, TIRAP, TLR2
37positive regulation of interleukin-12 productionGO:00327359.6CD36, TIRAP, TLR2, TLR4
38toll-like receptor TLR1:TLR2 signaling pathwayGO:00381239.6CD14, TLR1, TLR2
39positive regulation of interleukin-6 biosynthetic processGO:00454109.6TIRAP, TLR1, TLR6
40interleukin-1 beta secretionGO:00507029.6CD36, TLR4, TLR6
41apoptotic signaling pathwayGO:00971909.5BTK, CD14, LY96, TLR4
42I-kappaB kinase/NF-kappaB signalingGO:00072499.5BTK, CD14, LY96, TLR4
43positive regulation of NLRP3 inflammasome complex assemblyGO:19002279.5CD36, TLR4, TLR6
44positive regulation of NF-kappaB transcription factor activityGO:00510929.4BTK, MYD88, TIRAP, TLR2, TLR4
45lipopolysaccharide-mediated signaling pathwayGO:00316639.2CD14, LY96, MYD88, TLR2, TLR4
46toll-like receptor 4 signaling pathwayGO:00341429.2CD14, LY96, TIRAP, TLR4
47TRIF-dependent toll-like receptor signaling pathwayGO:00356669.1CD14, LY96, TLR4
48cellular response to lipoteichoic acidGO:00712239.1CD14, CD36, TIRAP, TLR2, TLR4
49cellular response to lipopolysaccharideGO:00712229.1CD14, CD36, LY96, TLR4, TLR5
50cell surface receptor signaling pathwayGO:00071669.0CD14, CD36, LY96, MYD88, TIRAP

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

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1interleukin-1 receptor bindingGO:000514910.3IRAK4, MYD88, TLR5
2lipopolysaccharide receptor activityGO:000187510.1LY96, TLR2, TLR4
3lipopolysaccharide bindingGO:00015309.9CD14, TLR2, TLR4
4lipopeptide bindingGO:00717239.6TLR1, TLR2, TLR6
5Toll-like receptor 2 bindingGO:00356639.5TIRAP, TLR1, TLR6
6receptor activityGO:00048729.0TLR1, TLR2, TLR4, TLR5, TLR6
7transmembrane signaling receptor activityGO:00048887.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6

Sources for Irak4 Deficiency

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31ICD10 via Orphanet
40MESH via Orphanet
53OMIM via Orphanet
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
69UMLS via Orphanet