HIGM5
MCID: IMM176
MIFTS: 41

Immunodeficiency with Hyper-Igm, Type 5 (HIGM5)

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

Aliases & Classifications for Immunodeficiency with Hyper-Igm, Type 5

MalaCards integrated aliases for Immunodeficiency with Hyper-Igm, Type 5:

Name: Immunodeficiency with Hyper-Igm, Type 5 56
Immunodeficiency with Hyper Igm Type 5 12 52 29 6 15
Higm5 56 12 52 58 73
Hyper-Igm Syndrome 5 56 12 73
Hyper-Igm Syndrome Due to Uracil N-Glycosylase 12 58
Hyper-Igm Syndrome Due to Ung Deficiency 12 58
Immunodeficiency with Hyper Igm, Type 5 56 13
Hyper-Igm Immunodeficiency Syndrome, Type 5 71
Immunodeficiency, with Hyper Igm, Type 5 39
Immunodeficiency with Hyper-Igm 5 73
Hyper-Igm Immunodeficiency Type 5 73
Hyper-Igm Syndrome Type 5 58
Hyper Igm Syndrome 5 52

Characteristics:

OMIM:

56
Miscellaneous:
recurrent bacterial infections

Inheritance:
autosomal recessive


HPO:

31
immunodeficiency with hyper-igm, type 5:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0060759
OMIM 56 608106
OMIM Phenotypic Series 56 PS308230
MeSH 43 D053306
ICD10 32 D80.5
ICD10 via Orphanet 33 D80.5
UMLS via Orphanet 72 C1720958
Orphanet 58 ORPHA101092
MedGen 41 C1720958
UMLS 71 C1720958

Summaries for Immunodeficiency with Hyper-Igm, Type 5

Disease Ontology : 12 A hyper IgM syndrome that is characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process that has material basis in homozygous or compound heterozygous mutation in the UNG gene on chromosome 12q23-q24.1.

MalaCards based summary : Immunodeficiency with Hyper-Igm, Type 5, also known as immunodeficiency with hyper igm type 5, is related to congenital rubella and orbital disease. An important gene associated with Immunodeficiency with Hyper-Igm, Type 5 is UNG (Uracil DNA Glycosylase), and among its related pathways/superpathways are DNA Double-Strand Break Repair and DNA Damage. Affiliated tissues include b cells, lymph node and t cells, and related phenotypes are immunodeficiency and recurrent bacterial infections

OMIM : 56 Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230). (608106)

UniProtKB/Swiss-Prot : 73 Immunodeficiency with hyper-IgM 5: 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 5

Diseases related to Immunodeficiency with Hyper-Igm, Type 5 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 31)
# Related Disease Score Top Affiliating Genes
1 congenital rubella 10.2 UNG CD40LG
2 orbital disease 10.2 ERCC6 CD40LG
3 suppurative otitis media 10.2 ERCC6 CD40LG
4 human granulocytic anaplasmosis 10.1 LIG4 CD40LG
5 immunodeficiency with hyper-igm, type 1 10.0 UNG CD40LG AICDA
6 schuurs-hoeijmakers syndrome 10.0 UNG CD40LG AICDA
7 severe combined immunodeficiency with sensitivity to ionizing radiation 10.0 PAXX LIG4
8 lig4 syndrome 10.0 MRE11 LIG4
9 combined t cell and b cell immunodeficiency 9.9 LIG4 CD40LG
10 omenn syndrome 9.9 LIG4 CD40LG AICDA
11 autosomal dominant non-syndromic intellectual disability 9.9 UNG CD40LG AICDA
12 transient hypogammaglobulinemia of infancy 9.8 TNFRSF13B CD40LG
13 seckel syndrome 9.8 MRE11 LIG4 ERCC6
14 nijmegen breakage syndrome 9.8 MRE11 LIG4 AICDA
15 immunoglobulin a deficiency 1 9.8 TNFRSF13B CD40LG
16 selective immunoglobulin deficiency disease 9.8 TNFRSF13B CD40LG
17 good syndrome 9.8 TNFRSF13B CD40LG
18 dysgammaglobulinemia 9.8 TNFRSF13B CD40LG
19 thrombocytopenia due to platelet alloimmunization 9.8 TNFRSF13B CD40LG
20 cranial nerve disease 9.7 ERCC6 CD40LG
21 lynch syndrome 9.7 MRE11 LIG4 ERCC6
22 macroglobulinemia 9.6 TNFRSF13B CD40LG
23 xeroderma pigmentosum, variant type 9.6 UNG LIG4 ERCC6
24 immunodeficiency with hyper-igm, type 3 9.6 TNFRSF13B CD40LG AICDA
25 immunoglobulin alpha deficiency 9.6 TNFRSF13B CD40LG AICDA
26 cd40 ligand deficiency 9.6 TNFRSF13B CD40LG AICDA
27 b cell deficiency 9.6 TNFRSF13B CD40LG AICDA
28 immunodeficiency with hyper-igm, type 4 9.5 UNG LIG4 ERCC6 CD40LG AICDA
29 common variable immunodeficiency 9.4 TNFRSF13B CD40LG AICDA
30 immunodeficiency with hyper-igm, type 2 9.4 UNG TNFRSF13B CD40LG AICDA
31 immune deficiency disease 9.1 UNG TNFRSF13B LIG4 CD40LG AICDA

Graphical network of the top 20 diseases related to Immunodeficiency with Hyper-Igm, Type 5:



Diseases related to Immunodeficiency with Hyper-Igm, Type 5

Symptoms & Phenotypes for Immunodeficiency with Hyper-Igm, Type 5

Human phenotypes related to Immunodeficiency with Hyper-Igm, Type 5:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 31 HP:0002721
2 recurrent bacterial infections 31 HP:0002718
3 decreased circulating iga level 31 HP:0002720
4 decreased circulating igg level 31 HP:0004315
5 lymphadenopathy 31 HP:0002716
6 recurrent upper and lower respiratory tract infections 31 HP:0200117
7 epididymitis 31 HP:0000031
8 increased circulating igm level 31 HP:0003496
9 impaired ig class switch recombination 31 HP:0002959

Symptoms via clinical synopsis from OMIM:

56
Respiratory:
recurrent upper and lower respiratory tract infections

Genitourinary Internal Genitalia Male:
chronic epididymitis

Immunology:
impaired ig class switch recombination (csr)
lymph node hyperplasia
normal b-cell (cd19+) count
elevated igm
low igg and iga

Clinical features from OMIM:

608106

GenomeRNAi Phenotypes related to Immunodeficiency with Hyper-Igm, Type 5 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 9.02 ERCC6 LIG4 MRE11 SMUG1 UNG

MGI Mouse Phenotypes related to Immunodeficiency with Hyper-Igm, Type 5:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.97 AICDA CD40LG ERCC6 LIG4 MRE11 PAXX
2 hematopoietic system MP:0005397 9.92 AICDA CD40LG ERCC6 LIG4 MRE11 PAXX
3 homeostasis/metabolism MP:0005376 9.91 AICDA CD40LG ERCC6 LIG4 MRE11 PAXX
4 immune system MP:0005387 9.76 AICDA CD40LG ERCC6 LIG4 MRE11 PAXX
5 mortality/aging MP:0010768 9.61 AICDA CD40LG ERCC6 LIG4 MRE11 PAXX
6 neoplasm MP:0002006 9.23 AICDA ERCC6 LIG4 MRE11 PAXX SMUG1

Drugs & Therapeutics for Immunodeficiency with Hyper-Igm, Type 5

Search Clinical Trials , NIH Clinical Center for Immunodeficiency with Hyper-Igm, Type 5

Genetic Tests for Immunodeficiency with Hyper-Igm, Type 5

Genetic tests related to Immunodeficiency with Hyper-Igm, Type 5:

# Genetic test Affiliating Genes
1 Immunodeficiency with Hyper Igm Type 5 29 UNG

Anatomical Context for Immunodeficiency with Hyper-Igm, Type 5

MalaCards organs/tissues related to Immunodeficiency with Hyper-Igm, Type 5:

40
B Cells, Lymph Node, T Cells

Publications for Immunodeficiency with Hyper-Igm, Type 5

Articles related to Immunodeficiency with Hyper-Igm, Type 5:

# Title Authors PMID Year
1
Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. 56 6
12958596 2003
2
B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil. 6
15967827 2005

Variations for Immunodeficiency with Hyper-Igm, Type 5

ClinVar genetic disease variations for Immunodeficiency with Hyper-Igm, Type 5:

6 (show all 21) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 UNG UNG, 1-BP DEL, 462Cdeletion Pathogenic 12290
2 UNG UNG, 2-BP DEL, 639TAdeletion Pathogenic 12291
3 UNG NM_080911.3(UNG):c.752T>C (p.Phe251Ser)SNV Pathogenic 12292 rs104894380 12:109541367-109541367 12:109103562-109103562
4 UNG UNG, 2-BP DEL, 497ATdeletion Pathogenic 12293
5 UNG NM_080911.3(UNG):c.685C>T (p.Arg229Ter)SNV Pathogenic 578381 rs772214871 12:109541300-109541300 12:109103495-109103495
6 UNG NM_080911.3(UNG):c.533+6G>ASNV Conflicting interpretations of pathogenicity 306973 rs55812333 12:109539810-109539810 12:109102005-109102005
7 UNG NM_080911.3(UNG):c.262C>T (p.Arg88Cys)SNV Uncertain significance 440391 rs151095402 12:109536366-109536366 12:109098561-109098561
8 UNG NM_080911.3(UNG):c.265A>G (p.Asn89Asp)SNV Uncertain significance 532544 rs201031933 12:109536369-109536369 12:109098564-109098564
9 UNG NM_080911.3(UNG):c.911G>A (p.Gly304Asp)SNV Uncertain significance 532545 rs1555265484 12:109547743-109547743 12:109109938-109109938
10 UNG NM_080911.3(UNG):c.651G>A (p.Thr217=)SNV Uncertain significance 573856 rs141783420 12:109541266-109541266 12:109103461-109103461
11 UNG NM_080911.3(UNG):c.*70_*71deldeletion Uncertain significance 36893 rs193922714 12:109547842-109547843 12:109110037-109110038
12 UNG NM_080911.3(UNG):c.61G>A (p.Ala21Thr)SNV Uncertain significance 643750 12:109535545-109535545 12:109097740-109097740
13 UNG NM_080911.3(UNG):c.260C>T (p.Ala87Val)SNV Uncertain significance 646511 12:109536364-109536364 12:109098559-109098559
14 UNG NM_080911.3(UNG):c.366A>C (p.Arg122Ser)SNV Uncertain significance 652008 12:109537020-109537020 12:109099215-109099215
15 UNG NM_080911.3(UNG):c.593A>G (p.His198Arg)SNV Uncertain significance 648895 12:109540703-109540703 12:109102898-109102898
16 UNG NM_080911.3(UNG):c.805C>T (p.Arg269Trp)SNV Uncertain significance 648430 12:109547637-109547637 12:109109832-109109832
17 UNG NM_080911.3(UNG):c.802-6T>CSNV Uncertain significance 639461 12:109547628-109547628 12:109109823-109109823
18 UNG NC_000012.11:g.(?_109547614)_(109547794_?)dupduplication Uncertain significance 645881 12:109547614-109547794 12:109109809-109109989
19 UNG NM_080911.3(UNG):c.544A>G (p.Ile182Val)SNV Uncertain significance 306974 rs545691651 12:109540654-109540654 12:109102849-109102849
20 UNG NM_080911.3(UNG):c.732G>A (p.Gln244=)SNV Likely benign 36895 rs193922715 12:109541347-109541347 12:109103542-109103542
21 UNG NM_080911.3(UNG):c.246G>C (p.Leu82=)SNV Benign/Likely benign 36894 rs144083363 12:109536350-109536350 12:109098545-109098545

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency with Hyper-Igm, Type 5:

73
# Symbol AA change Variation ID SNP ID
1 UNG p.Phe251Ser VAR_017094 rs104894380

Expression for Immunodeficiency with Hyper-Igm, Type 5

Search GEO for disease gene expression data for Immunodeficiency with Hyper-Igm, Type 5.

Pathways for Immunodeficiency with Hyper-Igm, Type 5

Pathways related to Immunodeficiency with Hyper-Igm, Type 5 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.56 UNG SMUG1 MRE11 LIG4 ERCC6
2 12.02 PAXX MRE11 LIG4
3
Show member pathways
11.96 UNG SMUG1 MRE11 LIG4 ERCC6
4 11.23 CD40LG AICDA
5 11.13 TNFRSF13B CD40LG
6 10.7 MRE11 LIG4
7
Show member pathways
10.64 UNG SMUG1
8 10.5 UNG TNFRSF13B CD40LG AICDA

GO Terms for Immunodeficiency with Hyper-Igm, Type 5

Cellular components related to Immunodeficiency with Hyper-Igm, Type 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.5 UNG SMUG1 RBM15B PAXX MRE11 LIG4
2 site of double-strand break GO:0035861 9.16 PAXX MRE11
3 nonhomologous end joining complex GO:0070419 8.62 PAXX LIG4

Biological processes related to Immunodeficiency with Hyper-Igm, Type 5 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.63 UNG SMUG1 PAXX MRE11 LIG4 ERCC6
2 activation of JUN kinase activity GO:0007257 9.54 ERCC6 CD40LG
3 chromosome organization GO:0051276 9.52 MRE11 LIG4
4 response to gamma radiation GO:0010332 9.51 LIG4 ERCC6
5 double-strand break repair via nonhomologous end joining GO:0006303 9.5 PAXX MRE11 LIG4
6 response to X-ray GO:0010165 9.49 LIG4 ERCC6
7 somatic hypermutation of immunoglobulin genes GO:0016446 9.48 UNG AICDA
8 single strand break repair GO:0000012 9.46 LIG4 ERCC6
9 depyrimidination GO:0045008 9.43 UNG SMUG1
10 base-excision repair GO:0006284 9.43 UNG SMUG1 ERCC6
11 DNA repair GO:0006281 9.43 UNG SMUG1 PAXX MRE11 LIG4 ERCC6
12 double-strand break repair via classical nonhomologous end joining GO:0097680 9.4 LIG4 ERCC6
13 DNA ligation involved in DNA repair GO:0051103 9.37 PAXX LIG4
14 isotype switching GO:0045190 8.92 UNG LIG4 CD40LG AICDA

Molecular functions related to Immunodeficiency with Hyper-Igm, Type 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.85 UNG TNFRSF13B SMUG1 RBM15B PAXX MRE11
2 hydrolase activity GO:0016787 9.65 UNG SMUG1 MRE11 ERCC6 AICDA
3 protein C-terminus binding GO:0008022 9.13 MRE11 LIG4 ERCC6
4 uracil DNA N-glycosylase activity GO:0004844 8.62 UNG SMUG1

Sources for Immunodeficiency with Hyper-Igm, Type 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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