MCID: IRK001
MIFTS: 46

Irak4 Deficiency malady

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

Aliases & Classifications for Irak4 Deficiency

About this section

Aliases & Descriptions for Irak4 Deficiency:

Name: Irak4 Deficiency 50 46 23 24 52 68 25 12 66
Interleukin-1 Receptor-Associated Kinase 4 Deficiency 24 66
Irak-4 Deficiency 46 24
Irak4d 23 68
 
Immunodeficiency Due to Interleukin-1 Receptor-Associated Kinase-4 Deficiency 52
Interleukin Receptor-Associated Kinase Deficiency 46
Interleukin 1 Receptor-Associated Kinase 4 12

Characteristics:

Orphanet epidemiological data:

52
irak4 deficiency:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: any age

Classifications:



External Ids:

OMIM50 607676
Orphanet52 ORPHA70592
ICD10 via Orphanet29 D84.8
MedGen35 C1843256

Summaries for Irak4 Deficiency

About this section
NIH Rare Diseases:46 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:68 IRAK4 deficiency: Causes extracellular pyogenic bacterial and fungal infections in otherwise healthy children.

Genetics Home Reference:24 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:50 IRAK4 deficiency is an autosomal recessive primary immunodeficiency that impairs Toll (see TLR4; 603030)/IL1R (see... (607676) more...

Related Diseases for Irak4 Deficiency

About this section

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

(show all 50)
idRelated DiseaseScoreTop Affiliating Genes
1fibrosis of extraocular muscles, congenital, 110.5IRAK4, TIRAP
2sinonasal undifferentiated carcinoma10.5TLR2, TLR4
3rickettsialpox10.5TLR2, TLR4
4atrial septal defect coronary sinus10.5TLR2, TLR4
5queensland tick typhus10.5MYD88, TLR2
6oculo cerebro osseous syndrome10.5TLR1, TLR5
7antigen-peptide-transporter 2 deficiency10.5TLR2, TLR4
8fanconi syndrome10.5TLR2, TLR4
9pernicious anemia10.4TLR2, TLR4
10mycobacterium fortuitum10.4TLR1, TLR2
11generalized atherosclerosis10.4BTK, MYD88
12toxocariasis10.4MYD88, TLR2, TLR4
13hepatic vein thrombosis10.4TLR2, TLR4, TLR5
14binocular vision disease10.3MYD88, TLR2, TLR4
15gastroduodenal crohn's disease10.3TLR2, TLR4, TLR5
16spondylohypoplasia, arthrogryposis and popliteal pterygium10.3TLR2, TLR4
17gallbladder lymphoma10.3TLR2, TLR4, TLR5
18plasmodium malariae malaria10.3IRAK4, MYD88
19uterine inversion10.3MYD88, TLR2, TLR4
20sheehan syndrome10.3IRAK4, TLR2, TLR4
21inner ear cancer10.3TLR2, TLR4
22bartonellosis10.3TLR1, TLR2, TLR4
23atrial tachyarrhythmia with short pr interval10.3TIRAP, TLR2
24mycobacterium gordonae10.3CD14, TLR2
25mycobacterium xenopi10.2CD14, TLR2
26acute cholangitis10.2TLR2, TLR4
27bacteremia10.2TIRAP, TLR2, TLR4
28paraneoplastic polyneuropathy10.2LY96, TLR2, TLR4
29accessory nerve disease10.1TLR2, TLR4
30nasopharyngitis10.1MYD88, TLR2, TLR4, TLR5
31pericarditis10.0
32pleural empyema10.0
33choline deficiency disease10.0TLR4, TLR6
34atopy9.9CD14, TLR2, TLR4
35pneumonia9.9
36hyper ige syndrome9.9
37askin's tumor9.8TIRAP, TLR2
38nevus mucinosis9.8TLR1, TLR2, TLR6
39trichosporonosis9.8TLR1, TLR2, TLR6
40tinea barbae9.8TLR1, TLR4, TLR6
41parametrium malignant neoplasm9.7TLR1, TLR2, TLR6
42abducens nerve neoplasm9.6TIRAP, TLR1, TLR2, TLR4, TLR5
43motion sickness9.6TLR10, TLR4, TLR6
44gastric ulcer9.5TLR1, TLR2, TLR4, TLR6
45malaria9.4CD36, MYD88, TIRAP, TLR2, TLR4
46compensatory emphysema9.1TIRAP, TLR1, TLR2, TLR4, TLR6
47melioidosis9.1LY96, TLR1, TLR10, TLR2, TLR4, TLR5
48ovary transitional cell carcinoma8.8MYD88, TIRAP, TLR1, TLR2, TLR4, TLR6
49anal atresia, hypospadias, and penoscrotal inversion6.4BTK, CD14, CD36, IRAK4, LY96, MYD88
50invasive pneumococcal disease, recurrent isolated, 15.9BTK, CD14, CD36, IRAK4, LY96, MYD88

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



Diseases related to irak4 deficiency

Symptoms for Irak4 Deficiency

About this section


Clinical features from OMIM:

607676

Symptoms:

 52
  • neutropenia
  • recurrent bacterial infections
  • immunodeficiency
  • recurrent streptococcus pneumoniae infections
  • recurrent staphylococcal infections

HPO human phenotypes related to Irak4 Deficiency:

id Description Frequency HPO Source Accession
1 abnormality of neutrophils hallmark (90%) HP:0001874
2 abnormality of immune system physiology hallmark (90%) HP:0010978
3 abnormality of the lymphatic system hallmark (90%) HP:0100763
4 immunodeficiency HP:0002721

Drugs & Therapeutics for Irak4 Deficiency

About this section

Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Irak4 Deficiency

Genetic Tests for Irak4 Deficiency

About this section

Genetic tests related to Irak4 Deficiency:

id Genetic test Affiliating Genes
1 Irak4 Deficiency25 23 IRAK4

Anatomical Context for Irak4 Deficiency

About this section

MalaCards organs/tissues related to Irak4 Deficiency:

34
Neutrophil

Animal Models for Irak4 Deficiency or affiliated genes

About this section

MGI Mouse Phenotypes related to Irak4 Deficiency:

39
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053818.4BTK, CD36, MYD88, TLR2, TLR4, TLR5
2MP:00053758.1CD14, CD36, MYD88, TLR2, TLR4, TLR5
3MP:00053767.1BTK, CD14, CD36, IRAK4, MYD88, TIRAP
4MP:00053875.8BTK, CD14, CD36, IRAK4, LY96, MYD88
5MP:00053975.6BTK, CD14, CD36, IRAK4, LY96, MYD88

Publications for Irak4 Deficiency

About this section

Articles related to Irak4 Deficiency:

idTitleAuthorsYear
1
IRAK4 deficiency promotes cardiac remodeling induced by pressure overload. (26884959)
2015
2
Recurrent systemic pneumococcal disease and IRAK4 deficiency. (17984826)
2007

Variations for Irak4 Deficiency

About this section

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

68
id Symbol AA change Variation ID SNP ID
1IRAK4p.Arg12CysVAR_072888rs377584435
2IRAK4p.Gly298AspVAR_072892rs568782766

Clinvar genetic disease variations for Irak4 Deficiency:

5
id Gene Variation Type Significance SNP ID Assembly Location
1IRAK4NM_016123.3(IRAK4): c.34C> T (p.Arg12Cys)single nucleotide variantPathogenicrs377584435GRCh37Chr 12, 44161948: 44161948
2IRAK4IRAK4, IVS7DS, G-T, +5single nucleotide variantPathogenic
3IRAK4IRAK4, 1-BP DEL, 821TdeletionPathogenic
4IRAK4NM_016123.3(IRAK4): c.877C> T (p.Gln293Ter)single nucleotide variantPathogenicrs121908002GRCh37Chr 12, 44172041: 44172041
5IRAK4IRAK4, 2-BP DEL, 620ACdeletionPathogenic

Expression for genes affiliated with Irak4 Deficiency

About this section
Search GEO for disease gene expression data for Irak4 Deficiency.

Pathways for genes affiliated with Irak4 Deficiency

About this section

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

(show all 41)
idSuper pathwaysScoreTop Affiliating Genes
19.9MYD88, TLR2
29.5IRAK4, MYD88, TIRAP
3
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
9
Show member pathways
9.0CD14, MYD88, TLR4, TLR5
10
Show member pathways
8.9IRAK4, LY96, MYD88, TLR2, TLR4
11
Show member pathways
8.8CD14, LY96, MYD88, TLR4
128.8CD14, LY96, MYD88, TLR4
13
Show member pathways
8.8CD14, LY96, TLR4, TLR5
14
Show member pathways
8.7BTK, CD14, LY96, TLR4
158.7CD14, MYD88, TLR2, TLR4, TLR5
168.6CD14, CD36, LY96, TLR4
17
Show member pathways
8.2CD14, IRAK4, LY96, MYD88, TIRAP, TLR4
18
Show member pathways
8.2CD14, IRAK4, LY96, MYD88, TIRAP, TLR4
198.2CD14, IRAK4, LY96, MYD88, TIRAP, TLR4
208.1BTK, IRAK4, MYD88, TLR1, TLR2, TLR6
217.9CD14, CD36, TLR2, TLR4, TLR6
22
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
237.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
247.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
25
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
26
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
27
Show member pathways
7.9TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
287.8BTK, CD14, IRAK4, LY96, MYD88, TIRAP
29
Show member pathways
7.4IRAK4, MYD88, TLR1, TLR10, TLR2, TLR4
30
Show member pathways
7.3BTK, IRAK4, TLR1, TLR10, TLR2, TLR4
317.1CD14, IRAK4, MYD88, TIRAP, TLR1, TLR2
32
Show member pathways
6.6BTK, IRAK4, MYD88, TIRAP, TLR1, TLR10
33
Show member pathways
6.4CD14, IRAK4, LY96, MYD88, TIRAP, TLR1
34
Show member pathways
6.4CD14, IRAK4, LY96, MYD88, TIRAP, TLR1
35
Show member pathways
6.4BTK, CD14, IRAK4, MYD88, TLR1, TLR10
36
Show member pathways
5.5BTK, CD14, IRAK4, LY96, MYD88, TIRAP
37
Show member pathways
5.0BTK, CD14, CD36, IRAK4, LY96, MYD88
38
Show member pathways
5.0BTK, CD14, CD36, IRAK4, LY96, MYD88
39
Show member pathways
5.0BTK, CD14, CD36, IRAK4, LY96, MYD88
40
Show member pathways
5.0BTK, CD14, CD36, IRAK4, LY96, MYD88
41
Show member pathways
5.0BTK, CD14, CD36, IRAK4, LY96, MYD88

GO Terms for genes affiliated with Irak4 Deficiency

About this section

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

idNameGO IDScoreTop Affiliating Genes
1Toll-like receptor 1-Toll-like receptor 2 protein complexGO:003535410.5TLR1, TLR2
2intrinsic component of plasma membraneGO:003122610.0LY96, TLR2, TLR4
3lipopolysaccharide receptor complexGO:00466969.8CD14, LY96, TLR4
4phagocytic vesicle membraneGO:00306709.4TLR1, TLR2, TLR6
5endosome membraneGO:00100089.1CD14, IRAK4, LY96, MYD88, TLR4
6Golgi apparatusGO:00057948.0CD14, CD36, TLR1, TLR2, TLR6
7membrane raftGO:00451217.8BTK, CD14, CD36, TLR1, TLR2, TLR6
8integral component of plasma membraneGO:00058877.4CD36, TLR1, TLR10, TLR2, TLR4, TLR5
9plasma membraneGO:00058864.7BTK, 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
1positive regulation of lymphocyte proliferationGO:005067110.6MYD88, TLR4
2positive regulation of toll-like receptor signaling pathwayGO:003412310.6TLR2, TLR5
3detection of triacyl bacterial lipopeptideGO:004249510.5TLR1, TLR2
43-UTR-mediated mRNA stabilizationGO:007093510.5MYD88, TIRAP
5detection of lipopolysaccharideGO:003249710.4LY96, TLR4
6positive regulation of tumor necrosis factor biosynthetic processGO:004253510.4TLR1, TLR4
7macrophage activationGO:004211610.4TLR1, TLR4
8I-kappaB phosphorylationGO:000725210.4TLR2, TLR4
9positive regulation of macrophage cytokine productionGO:006090710.3CD36, TLR4
10cellular response to mechanical stimulusGO:007126010.2MYD88, TLR4, TLR5
11detection of diacyl bacterial lipopeptideGO:004249610.0TLR2, TLR6
12response to bacterial lipoproteinGO:003249310.0TLR2, TLR6
13T-helper 1 type immune responseGO:004208810.0TLR4, TLR6
14positive regulation of JNK cascadeGO:004633010.0MYD88, TIRAP, TLR4
15nitric oxide metabolic processGO:00462099.9TLR2, TLR6
16positive regulation of inflammatory responseGO:00507299.9TLR10, TLR2, TLR4
17cellular response to bacterial lipopeptideGO:00712219.9CD36, TIRAP, TLR2
18negative regulation of growth of symbiont in hostGO:00441309.8CD36, MYD88, TIRAP
19toll-like receptor TLR1:TLR2 signaling pathwayGO:00381239.8CD14, TLR1, TLR2
20cellular response to triacyl bacterial lipopeptideGO:00717279.8CD14, TLR1, TLR2
21MyD88-independent toll-like receptor signaling pathwayGO:00027569.7CD14, LY96, TLR4
22negative regulation of MyD88-independent toll-like receptor signaling pathwayGO:00341289.7CD14, LY96, TLR4
23TRIF-dependent toll-like receptor signaling pathwayGO:00356669.7CD14, LY96, TLR4
24positive regulation of interleukin-6 biosynthetic processGO:00454109.6TIRAP, TLR1, TLR6
25positive regulation of interleukin-12 productionGO:00327359.5CD36, TIRAP, TLR2, TLR4
26positive regulation of NLRP3 inflammasome complex assemblyGO:19002279.5CD36, TLR4, TLR6
27interleukin-1 beta secretionGO:00507029.5CD36, TLR4, TLR6
28positive regulation of interleukin-8 productionGO:00327579.4TIRAP, TLR2, TLR4, TLR5
29I-kappaB kinase/NF-kappaB signalingGO:00072499.3BTK, CD14, LY96, TLR4
30positive regulation of interleukin-6 productionGO:00327559.3CD36, MYD88, TLR2, TLR4
31toll-like receptor 4 signaling pathwayGO:00341429.3CD14, LY96, TIRAP, TLR4
32necroptotic processGO:00702669.2CD14, LY96, TLR4
33lipopolysaccharide-mediated signaling pathwayGO:00316639.1CD14, LY96, MYD88, TLR2, TLR4
34positive regulation of NF-kappaB transcription factor activityGO:00510929.1BTK, MYD88, TIRAP, TLR2, TLR4
35defense response to Gram-positive bacteriumGO:00508309.0CD36, MYD88, TIRAP, TLR2
36cellular response to lipoteichoic acidGO:00712238.9CD14, CD36, TIRAP, TLR2, TLR4
37apoptotic signaling pathwayGO:00971908.8BTK, CD14, LY96, TLR4
38cellular response to diacyl bacterial lipopeptideGO:00717268.8CD14, CD36, TLR2, TLR6
39toll-like receptor TLR6:TLR2 signaling pathwayGO:00381248.8CD14, CD36, TLR2, TLR6
40cellular response to lipopolysaccharideGO:00712228.8CD14, CD36, LY96, TLR4, TLR5
41regulation of cytokine secretionGO:00507078.6TLR1, TLR10, TLR2, TLR4, TLR5, TLR6
42positive regulation of I-kappaB kinase/NF-kappaB signalingGO:00431238.4CD36, IRAK4, MYD88, TIRAP, TLR4, TLR6
43response to lipopolysaccharideGO:00324968.2CD14, LY96, MYD88, TIRAP, TLR2, TLR4
44toll-like receptor signaling pathwayGO:00022248.2IRAK4, MYD88, TLR1, TLR10, TLR2, TLR4
45positive regulation of tumor necrosis factor productionGO:00327608.1CD14, CD36, LY96, MYD88, TIRAP, TLR2
46cell surface receptor signaling pathwayGO:00071667.9CD14, CD36, LY96, MYD88, TIRAP
47immune responseGO:00069557.6CD36, TLR1, TLR10, TLR2, TLR4, TLR6
48inflammatory responseGO:00069546.3CD14, LY96, MYD88, TIRAP, TLR1, TLR10
49innate immune responseGO:00450875.7BTK, CD14, IRAK4, LY96, MYD88, TIRAP
50MyD88-dependent toll-like receptor signaling pathwayGO:00027555.6BTK, CD14, CD36, IRAK4, LY96, MYD88

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

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1interleukin-1 receptor bindingGO:000514910.2IRAK4, MYD88, TLR5
2lipopolysaccharide receptor activityGO:00018759.9LY96, TLR2, TLR4
3Toll-like receptor 2 bindingGO:00356639.4TIRAP, TLR1, TLR6
4lipopeptide bindingGO:00717239.4TLR1, TLR2, TLR6
5lipopolysaccharide bindingGO:00015309.2CD14, TLR2, TLR4
6receptor activityGO:00048728.3TLR1, TLR2, TLR4, TLR5, TLR6
7transmembrane signaling receptor activityGO:00048887.6TLR1, TLR10, TLR2, TLR4, TLR5, TLR6

Sources for Irak4 Deficiency

About this section
2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet