IMD33
MCID: IMM099
MIFTS: 37

Immunodeficiency 33 (IMD33)

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

Aliases & Classifications for Immunodeficiency 33

MalaCards integrated aliases for Immunodeficiency 33:

Name: Immunodeficiency 33 57 12 20 72 15
X-Linked Mendelian Susceptibility to Mycobacterial Diseases Due to Ikbkg Deficiency 12 20 58
X-Linked Mendelian Susceptibility to Mycobacterial Diseases Due to Nemo Deficiency 12 20 58
X-Linked Msmd Due to Ikbkg Deficiency 12 20 58
Imd33 57 12 72
Familial Atypical Mycobacteriosis, Type 1, X-Linked 29 6
Atypical Mycobacteriosis, Familial, X-Linked 1 44 70
X-Linked Msmd Due to Nemo Deficiency 12 58
Invasive Pneumococcal Disease, Recurrent Isolated, 2, Formerly; Ipd2, Formerly 57
Invasive Pneumococcal Disease, Recurrent Isolated, 2, Formerly 57
X-Linked Disseminated Atypical Mycobacterial Infection Type 1 72
Invasive Pneumococcal Disease, Recurrent Isolated, Type 2 39
X-Linked Susceptibility to Mycobacterial Disease Type 1 72
Recurrent Isolated Invasive Pneumococcal Disease 2 72
Familial, X-Linked, Atypical Mycobacteriosis 1 72
X-Linked Immunodeficiency 33, Mycobacteriosis 72
Familial X-Linked 1 Atypical Mycobacteriosis 20
Nf-Kappa B Essential Modulator Deficiency 20
Nemo Deficiency Syndrome 20
Ipd2, Formerly 57
Amcbx1 72
Ipd2 72

Characteristics:

Orphanet epidemiological data:

58

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
highly variable severity
onset usually in infancy or early childhood
laboratory abnormalities may be subtle and may change over time
treatment with ivig is beneficial
carrier mothers may have conical teeth or hypodontia

Inheritance:
x-linked recessive


HPO:

31
immunodeficiency 33:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0112003
OMIM® 57 300636
OMIM Phenotypic Series 57 PS300755
ICD10 via Orphanet 33 D84.8
Orphanet 58 ORPHA319612
MedGen 41 C1970879
UMLS 70 C1970879

Summaries for Immunodeficiency 33

OMIM® : 57 Immunodeficiency-33 (IMD33) is an X-linked recessive disorder that affects only males. It is characterized by early-onset severe infections, usually due to pneumococcus, H. influenzae, and atypical mycobacteria, although other organisms have also been detected. Immunologic investigations may show variable abnormalities or may be normal. Disturbances include dysgammaglobulinemia with hypogammaglobulinemia, decreased IgG2, aberrant levels of IgM and IgA, and decreased class-switched memory B cells. There is often poor, but variable, response to vaccination; in particular, most patients do not develop antibodies to certain polysaccharide vaccines, notably pneumococcus. Other immunologic abnormalities may include impaired NK cytotoxic function, impaired cytokine production upon stimulation with IL1B (147720) or TNFA (191160), low IL6 (147620), low IL12 (see 161561), and decreased IFNG (147570). Patients do not have overt abnormalities of T-cell proliferation, although signaling pathways, such as CD40LG (300386)/CD40 (109535), may be disturbed. There is heterogeneity in the immunologic phenotype, resulting in highly variable clinical courses, most likely due to the different effects of hypomorphic mutations. Treatment with antibiotics and IVIg is usually beneficial; hematopoietic stem cell transplantation may not be necessary, but can be effective. Features of hypohidrotic ectodermal dysplasia are generally not present, although some patients may have conical teeth or hypodontia (summary by Orange et al., 2004, Filipe-Santos et al., 2006, Salt et al., 2008, Heller et al., 2020). (300636) (Updated 05-Apr-2021)

MalaCards based summary : Immunodeficiency 33, also known as x-linked mendelian susceptibility to mycobacterial diseases due to ikbkg deficiency, is related to non-alcoholic fatty liver disease and cd40 ligand deficiency. An important gene associated with Immunodeficiency 33 is IKBKG (Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma), and among its related pathways/superpathways are TCR Signaling (Qiagen) and Measles. Affiliated tissues include b cells, and related phenotypes are delayed eruption of teeth and hypodontia

Disease Ontology : 12 A combined immunodeficiency characterized by early-onset severe infection and variable immunological abnormalities that has material basis in hemizygous mutation in IKBKG on chromosome Xq28.

UniProtKB/Swiss-Prot : 72 Immunodeficiency 33: An X-linked recessive disorder characterized by variably impaired immunologic function and early-onset recurrent infections, usually due to pneumococcus, H. influenzae, and atypical mycobacteria. Features of hypohidrotic ectodermal dysplasia are generally not present, although some patients may have conical teeth or hypodontia.

Related Diseases for Immunodeficiency 33

Diseases related to Immunodeficiency 33 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 non-alcoholic fatty liver disease 10.2
2 cd40 ligand deficiency 9.6 IKBKG BTK
3 immunodeficiency with hyper-igm, type 1 9.6 IKBKG BTK
4 immune deficiency disease 9.5 IKBKG BTK

Symptoms & Phenotypes for Immunodeficiency 33

Human phenotypes related to Immunodeficiency 33:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 delayed eruption of teeth 31 occasional (7.5%) HP:0000684
2 hypodontia 31 very rare (1%) HP:0000668
3 conical tooth 31 very rare (1%) HP:0000698
4 decreased circulating total igm 31 very rare (1%) HP:0002850
5 increased circulating iga level 31 very rare (1%) HP:0003261
6 recurrent bacterial infections 31 very rare (1%) HP:0002718
7 immunodeficiency 31 HP:0002721
8 disseminated nontuberculous mycobacterial infection 31 HP:0032283

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Immunology:
recurrent infections
dysgammaglobulinemia
hypogammaglobulinemia
variably impaired immunologic function
increased igm (in some patients)
more
Head And Neck Teeth:
conical teeth (in some patients)
delayed eruption of teeth (in some patients)
hypodontia (in some patients)

Clinical features from OMIM®:

300636 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Immunodeficiency 33 according to GeneCards Suite gene sharing:

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-127 9.47 IKBKG
2 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.47 BTK
3 Increased shRNA abundance (Z-score > 2) GR00366-A-140 9.47 BTK
4 Increased shRNA abundance (Z-score > 2) GR00366-A-17 9.47 IKBKG
5 Increased shRNA abundance (Z-score > 2) GR00366-A-212 9.47 IKBKG
6 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.47 IKBKG
7 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.47 BTK
8 Increased shRNA abundance (Z-score > 2) GR00366-A-34 9.47 IKBKG
9 Increased shRNA abundance (Z-score > 2) GR00366-A-4 9.47 BTK
10 Increased shRNA abundance (Z-score > 2) GR00366-A-56 9.47 IKBKG
11 Increased shRNA abundance (Z-score > 2) GR00366-A-59 9.47 BTK
12 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.47 BTK
13 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.47 BTK
14 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.47 BTK

Drugs & Therapeutics for Immunodeficiency 33

Search Clinical Trials , NIH Clinical Center for Immunodeficiency 33

Cochrane evidence based reviews: atypical mycobacteriosis, familial, x-linked 1

Genetic Tests for Immunodeficiency 33

Genetic tests related to Immunodeficiency 33:

# Genetic test Affiliating Genes
1 Familial Atypical Mycobacteriosis, Type 1, X-Linked 29 IKBKG

Anatomical Context for Immunodeficiency 33

MalaCards organs/tissues related to Immunodeficiency 33:

40
B Cells

Publications for Immunodeficiency 33

Articles related to Immunodeficiency 33:

(show all 16)
# Title Authors PMID Year
1
T Cell Impairment Is Predictive for a Severe Clinical Course in NEMO Deficiency. 6 57
31965418 2020
2
IKBKG (NEMO) 5' Untranslated Splice Mutations Lead to Severe, Chronic Disseminated Mycobacterial Infections. 57 6
29534156 2018
3
Functional Evaluation of an IKBKG Variant Suspected to Cause Immunodeficiency Without Ectodermal Dysplasia. 57 6
28993958 2017
4
Successful hematopoietic cell transplantation in patients with unique NF-κB essential modulator (NEMO) mutations. 57 6
25068423 2014
5
IKBKG (nuclear factor-kappa B essential modulator) mutation can be associated with opportunistic infection without impairing Toll-like receptor function. 6 57
18179816 2008
6
IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease. 57 6
16950813 2007
7
X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production. 6 57
16818673 2006
8
The NEMO mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation. 6 57
16532398 2006
9
NEMO mutations in 2 unrelated boys with severe infections and conical teeth. 57 6
15833888 2005
10
Nuclear factor kappaB essential modulator-deficient child with immunodeficiency yet without anhidrotic ectodermal dysplasia. 57 6
15577852 2004
11
Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation. 57 6
15229184 2004
12
Rescue of recurrent deep intronic mutation underlying cell type-dependent quantitative NEMO deficiency. 57
30422821 2019
13
Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia. 57
15356572 2004
14
The presentation and natural history of immunodeficiency caused by nuclear factor kappaB essential modulator mutation. 57
15100680 2004
15
Pushing the limits of the scanning mechanism for initiation of translation. 6
12459250 2002
16
Hepatic NF-kappa B essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis. 61
18216263 2008

Variations for Immunodeficiency 33

ClinVar genetic disease variations for Immunodeficiency 33:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 IKBKG NM_003639.4(IKBKG):c.111dup (p.Met38fs) Duplication Pathogenic 11465 rs1569556522 GRCh37: X:153780326-153780327
GRCh38: X:154552111-154552112
2 IKBKG NM_003639.4(IKBKG):c.944A>C (p.Glu315Ala) SNV Pathogenic 11467 rs137853331 GRCh37: X:153791805-153791805
GRCh38: X:154563590-154563590
3 IKBKG NM_003639.4(IKBKG):c.956G>A (p.Arg319Gln) SNV Pathogenic 11468 rs137853332 GRCh37: X:153791817-153791817
GRCh38: X:154563602-154563602
4 IKBKG NM_003639.4(IKBKG):c.517C>G (p.Arg173Gly) SNV Pathogenic 11469 rs179363866 GRCh37: X:153786864-153786864
GRCh38: X:154558649-154558649
5 IKBKG NM_001099857.5(IKBKG):c.811_828del (p.Glu271_Ala276del) Deletion Pathogenic 916676 GRCh37: X:153791063-153791080
GRCh38: X:154562848-154562865
6 IKBKG NM_001099857.5(IKBKG):c.239T>C (p.Leu80Pro) SNV Pathogenic 916677 GRCh37: X:153784431-153784431
GRCh38: X:154556216-154556216
7 IKBKG NM_001099857.5(IKBKG):c.-16+344G>C SNV Pathogenic 916681 GRCh37: X:153776304-153776304
GRCh38: X:154548089-154548089
8 IKBKG NM_001099857.5(IKBKG):c.169G>A (p.Glu57Lys) SNV Pathogenic 68234 rs148695964 GRCh37: X:153780386-153780386
GRCh38: X:154552171-154552171
9 IKBKG NM_001099857.5(IKBKG):c.337G>A (p.Asp113Asn) SNV Pathogenic 68235 rs179363896 GRCh37: X:153784529-153784529
GRCh38: X:154556314-154556314
10 G6PD , IKBKG NM_001360016.2(G6PD):c.120+3646C>T SNV Uncertain significance 625962 rs782367664 GRCh37: X:153770605-153770605
GRCh38: X:154542390-154542390

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 33:

72
# Symbol AA change Variation ID SNP ID
1 IKBKG p.Cys417Tyr VAR_026496 rs137853326
2 IKBKG p.Arg173Gly VAR_031958 rs179363866
3 IKBKG p.Glu315Ala VAR_031959 rs137853331
4 IKBKG p.Arg319Gln VAR_031960 rs137853332

Expression for Immunodeficiency 33

Search GEO for disease gene expression data for Immunodeficiency 33.

Pathways for Immunodeficiency 33

Pathways related to Immunodeficiency 33 according to GeneCards Suite gene sharing:

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.34 IKBKG BTK
2
Show member pathways
12.27 IKBKG BTK
3
Show member pathways
12.19 IKBKG BTK
4
Show member pathways
12.12 IKBKG BTK
5
Show member pathways
12.09 IKBKG BTK
6
Show member pathways
12.04 IKBKG BTK
7 12.01 IKBKG BTK
8
Show member pathways
11.9 IKBKG BTK
9
Show member pathways
11.85 IKBKG BTK
10
Show member pathways
11.83 IKBKG BTK
11
Show member pathways
11.71 IKBKG BTK
12
Show member pathways
11.65 IKBKG BTK
13
Show member pathways
11.56 IKBKG BTK
14 11.36 IKBKG BTK
15 11.25 IKBKG BTK
16 10.97 IKBKG BTK
17 10.2 IKBKG BTK

GO Terms for Immunodeficiency 33

Biological processes related to Immunodeficiency 33 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apoptotic process GO:0006915 9.32 IKBKG BTK
2 innate immune response GO:0045087 9.26 IKBKG BTK
3 Fc-epsilon receptor signaling pathway GO:0038095 9.16 IKBKG BTK
4 positive regulation of NF-kappaB transcription factor activity GO:0051092 8.96 IKBKG BTK
5 I-kappaB kinase/NF-kappaB signaling GO:0007249 8.62 IKBKG BTK

Sources for Immunodeficiency 33

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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