MCID: IMM105
MIFTS: 42

Immunodeficiency with Hyper-Igm, Type 3

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

Aliases & Classifications for Immunodeficiency with Hyper-Igm, Type 3

MalaCards integrated aliases for Immunodeficiency with Hyper-Igm, Type 3:

Name: Immunodeficiency with Hyper-Igm, Type 3 57 13
Higm3 57 53 59 75 55
Immunodeficiency with Hyper Igm Type 3 53 29 6
Hyper-Igm Syndrome Due to Cd40 Deficiency 12 59
Hyper-Igm Syndrome 3 57 75
Cd40 Deficiency 12 15
Hyper-Igm Immunodeficiency Syndrome, Type 3 73
Immunodeficiency, with Hyper Igm, Type 3 40
Immunodeficiency with Hyper-Igm Type 3 12
Type 3 Hyper-Igm Immunodeficiency 12
Immunodeficiency with Hyper-Igm 3 75
Hyper-Igm Immunodeficiency Type 3 75
Hyper-Igm Syndrome Type 3 59
Hyper Igm Syndrome 3 53

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
increased susceptibility to bacterial and opportunistic infections, such as pneumocystis carinii


HPO:

32
immunodeficiency with hyper-igm, type 3:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


External Ids:

OMIM 57 606843
Disease Ontology 12 DOID:0060023
Orphanet 59 ORPHA101090
ICD10 via Orphanet 34 D80.5
UMLS via Orphanet 74 C1720957
MedGen 42 C1720957
MeSH 44 D053306
UMLS 73 C1720957

Summaries for Immunodeficiency with Hyper-Igm, Type 3

Disease Ontology : 12 A combined T cell and B cell immunodeficiency that has material basis in mutation in the TNFRSF5 gene, resulting in type 3 hyper-IgM immunodeficiency characterized by an inability of B cells to undergo isotype switching, an inability to mount an antibody-specific immune response, and a lack of germinal center formation.

MalaCards based summary : Immunodeficiency with Hyper-Igm, Type 3, also known as higm3, is related to light fixation seizure syndrome and immunodeficiency with hyper-igm, type 1. An important gene associated with Immunodeficiency with Hyper-Igm, Type 3 is CD40 (CD40 Molecule), and among its related pathways/superpathways are Cytokine Signaling in Immune system and Allograft rejection. Affiliated tissues include b cells, t cells and lymph node, and related phenotypes are immunodeficiency and neutropenia

OMIM : 57 HIGM3, first described in humans by Ferrari et al. (2001), is characterized by hypogammaglobulinemia with normal or elevated levels of IgM. For a general phenotypic description and a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230). (606843)

UniProtKB/Swiss-Prot : 75 Immunodeficiency with hyper-IgM 3: A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.

Related Diseases for Immunodeficiency with Hyper-Igm, Type 3

Diseases related to Immunodeficiency with Hyper-Igm, Type 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 31)
# Related Disease Score Top Affiliating Genes
1 light fixation seizure syndrome 29.8 CD40 CD40LG
2 immunodeficiency with hyper-igm, type 1 29.4 AICDA CD40 CD40LG
3 hyperimmunoglobulin syndrome 29.0 AICDA CD40 CD40LG
4 exanthema subitum 10.1 CD40 CD40LG
5 waldenstrom macroglobulinemia 10.1 CD40 CD40LG
6 salivary gland disease 10.0 CD40LG RAG1
7 progressive multifocal leukoencephalopathy 9.9 CD40LG RAG1
8 toxoplasmosis 9.8 CD40 CD40LG
9 immunodeficiency with hyper-igm, type 4 9.7 AICDA CD40 CD40LG
10 cd40 ligand deficiency 9.7 AICDA CD40 CD40LG
11 myocarditis 9.7 CD40 CD40LG
12 immunodeficiency with hyper-igm, type 2 9.7 AICDA CD40 CD40LG
13 mature b-cell neoplasm 9.7 AICDA CD40 CD40LG
14 coccidioidomycosis 9.7 CARD9 CD40LG
15 b cell deficiency 9.7 AICDA CD40 CD40LG
16 immunodeficiency 17 9.7 CARD9 CD40LG
17 burkitt lymphoma 9.7 AICDA CD40 CD40LG
18 primary systemic mycosis 9.6 CARD9 CD40LG
19 lymphoma, non-hodgkin, familial 9.6 AICDA CD40 CD40LG
20 alzheimer disease 9.6
21 diabetes mellitus, noninsulin-dependent 9.6
22 fatty liver disease, nonalcoholic 1 9.6
23 hematopoietic stem cell transplantation 9.6
24 hepatitis 9.6
25 combined immunodeficiency, x-linked 9.6 CD40 CD40LG RAG1
26 immune deficiency disease 9.6 CD40 CD40LG RAG1
27 follicular lymphoma 9.6 AICDA CD40
28 meningoencephalitis 9.5 CARD9 CD40LG
29 opportunistic mycosis 9.5 CARD9 CD40LG
30 leukemia, chronic lymphocytic 9.4 AICDA CD40 CD40LG
31 common variable immunodeficiency 9.1 AICDA CD40 CD40LG RAG1

Graphical network of the top 20 diseases related to Immunodeficiency with Hyper-Igm, Type 3:



Diseases related to Immunodeficiency with Hyper-Igm, Type 3

Symptoms & Phenotypes for Immunodeficiency with Hyper-Igm, Type 3

Symptoms via clinical synopsis from OMIM:

57
Hematology:
neutropenia

Immunology:
normal or increased igm
serum iga, igg, and ige severely deficient
lymph nodes lack germinal centers
primary dysfunction of b-lymphocyte isotype switching and memory b-cell generation


Clinical features from OMIM:

606843

Human phenotypes related to Immunodeficiency with Hyper-Igm, Type 3:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 32 HP:0002721
2 neutropenia 32 HP:0001875
3 recurrent bacterial infections 32 HP:0002718
4 iga deficiency 32 HP:0002720
5 igg deficiency 32 HP:0004315
6 increased igm level 32 HP:0003496
7 absence of lymph node germinal center 32 HP:0002849
8 impaired memory b cell generation 32 HP:0002847
9 impaired ig class switch recombination 32 HP:0002959
10 ige deficiency 32 HP:0005479

MGI Mouse Phenotypes related to Immunodeficiency with Hyper-Igm, Type 3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.63 AICDA CARD9 CD40 CD40LG RAG1 TRAF6
2 immune system MP:0005387 9.43 AICDA CARD9 CD40 CD40LG RAG1 TRAF6
3 renal/urinary system MP:0005367 8.92 CD40 CD40LG RAG1 TRAF6

Drugs & Therapeutics for Immunodeficiency with Hyper-Igm, Type 3

Search Clinical Trials , NIH Clinical Center for Immunodeficiency with Hyper-Igm, Type 3

Genetic Tests for Immunodeficiency with Hyper-Igm, Type 3

Genetic tests related to Immunodeficiency with Hyper-Igm, Type 3:

# Genetic test Affiliating Genes
1 Immunodeficiency with Hyper Igm Type 3 29 CD40

Anatomical Context for Immunodeficiency with Hyper-Igm, Type 3

MalaCards organs/tissues related to Immunodeficiency with Hyper-Igm, Type 3:

41
B Cells, T Cells, Lymph Node

Publications for Immunodeficiency with Hyper-Igm, Type 3

Articles related to Immunodeficiency with Hyper-Igm, Type 3:

# Title Authors Year
1
Clinical, immunological, and molecular characterization of hyper-IgM syndrome due to CD40 deficiency in eleven patients. ( 24122029 )
2013

Variations for Immunodeficiency with Hyper-Igm, Type 3

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency with Hyper-Igm, Type 3:

75
# Symbol AA change Variation ID SNP ID
1 CD40 p.Cys83Arg VAR_013628 rs28931586
2 CD40 p.Cys37Gly VAR_077569

ClinVar genetic disease variations for Immunodeficiency with Hyper-Igm, Type 3:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CD40 CD40, 455A-T, +5, EX5 single nucleotide variant Pathogenic
2 CD40 NM_001250.5(CD40): c.247T> C (p.Cys83Arg) single nucleotide variant Pathogenic rs28931586 GRCh37 Chromosome 20, 44750988: 44750988
3 CD40 NM_001250.5(CD40): c.247T> C (p.Cys83Arg) single nucleotide variant Pathogenic rs28931586 GRCh38 Chromosome 20, 46122349: 46122349
4 CD40 CD40, IVS3, A-T, -2 single nucleotide variant Pathogenic
5 CD40 CD40, 3-BP DEL, 175TAA deletion Pathogenic
6 CD40 NM_001250.5(CD40): c.-1T> C single nucleotide variant Benign rs1883832 GRCh37 Chromosome 20, 44746982: 44746982
7 CD40 NM_001250.5(CD40): c.-1T> C single nucleotide variant Benign rs1883832 GRCh38 Chromosome 20, 46118343: 46118343

Expression for Immunodeficiency with Hyper-Igm, Type 3

Search GEO for disease gene expression data for Immunodeficiency with Hyper-Igm, Type 3.

Pathways for Immunodeficiency with Hyper-Igm, Type 3

Pathways related to Immunodeficiency with Hyper-Igm, Type 3 according to GeneCards Suite gene sharing:

(show all 19)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.98 CD40 CD40LG RAG1 TRAF6
2
Show member pathways
12.49 AICDA CD40 CD40LG
3
Show member pathways
12.33 CD40 CD40LG TRAF6
4
Show member pathways
12.27 CD40 CD40LG TRAF6
5
Show member pathways
12.08 CD40 CD40LG TRAF6
6 11.87 AICDA CARD9 CD40LG RAG1 TRAF6
7
Show member pathways
11.85 CD40 CD40LG TRAF6
8
Show member pathways
11.64 CARD9 TRAF6
9 11.48 CD40 CD40LG TRAF6
10 11.36 AICDA CD40LG
11
Show member pathways
11.35 CD40LG TRAF6
12
Show member pathways
11.3 CD40 CD40LG TRAF6
13 11.29 CD40 CD40LG
14 11.23 CD40 CD40LG
15 11.17 CD40 CD40LG
16 10.98 CD40 CD40LG
17 10.94 CD40 CD40LG
18 10.81 CD40 CD40LG TRAF6
19 10.49 AICDA CD40 CD40LG RAG1

GO Terms for Immunodeficiency with Hyper-Igm, Type 3

Cellular components related to Immunodeficiency with Hyper-Igm, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 CD40 receptor complex GO:0035631 8.62 CD40 TRAF6

Biological processes related to Immunodeficiency with Hyper-Igm, Type 3 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 9.73 CARD9 CD40 TRAF6
2 regulation of apoptotic process GO:0042981 9.69 CARD9 CD40 TRAF6
3 defense response to virus GO:0051607 9.61 AICDA CARD9 CD40
4 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 9.58 CARD9 CD40 TRAF6
5 platelet activation GO:0030168 9.57 CD40 CD40LG
6 positive regulation of T cell proliferation GO:0042102 9.55 CD40LG TRAF6
7 I-kappaB kinase/NF-kappaB signaling GO:0007249 9.54 CARD9 TRAF6
8 protein autoubiquitination GO:0051865 9.52 RAG1 TRAF6
9 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.5 CD40 CD40LG TRAF6
10 B cell proliferation GO:0042100 9.49 CD40 CD40LG
11 positive regulation of interleukin-12 production GO:0032735 9.48 CD40 CD40LG
12 positive regulation of endothelial cell apoptotic process GO:2000353 9.46 CD40 CD40LG
13 immune response GO:0006955 9.46 CD40 CD40LG RAG1 TRAF6
14 cellular response to lipopolysaccharide GO:0071222 9.43 AICDA CD40 TRAF6
15 isotype switching GO:0045190 9.37 AICDA CD40LG
16 B cell differentiation GO:0030183 9.13 AICDA CD40LG RAG1
17 regulation of immunoglobulin secretion GO:0051023 8.8 CD40 CD40LG TRAF6

Molecular functions related to Immunodeficiency with Hyper-Igm, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ubiquitin protein ligase binding GO:0031625 9.13 AICDA CD40 TRAF6
2 tumor necrosis factor receptor binding GO:0005164 8.62 CD40LG TRAF6

Sources for Immunodeficiency with Hyper-Igm, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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