IMD28
MCID: IMM180
MIFTS: 39

Immunodeficiency 28 (IMD28)

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

Aliases & Classifications for Immunodeficiency 28

MalaCards integrated aliases for Immunodeficiency 28:

Name: Immunodeficiency 28 57 12 72 29 6 15 70
Ifngr2 Deficiency 57 12 72
Imd28 57 12 72
Mendelian Susceptibility to Mycobacterial Diseases Due to Complete Interferon Gamma Receptor 2 Deficiency 12 58
Mendelian Susceptibility to Mycobacterial Diseases Due to Complete Ifngammar2 Deficiency 12 58
Msmd Due to Complete Interferon Gamma Receptor 2 Deficiency 12 58
Immunodeficiency 28, Mycobacteriosis, Autosomal Recessive 57 72
Msmd Due to Complete Ifngammar2 Deficiency 12 58
Immunodeficiency 28, Mycobacteriosis 57 12
Autosomal Recessive Mendelian Susceptibility to Mycobacterial Diseases Due to Partial Interferon Gamma Receptor 2 Deficiency 58
Autosomal Recessive Mendelian Susceptibility to Mycobacterial Diseases Due to Partial Ifngammar2 Deficiency 58
Autosomal Recessive Msmd Due to Partial Interferon Gamma Receptor 2 Deficiency 58
Autosomal Recessive Msmd Due to Partial Ifngammar2 Deficiency 58
Immunodeficiency, Type 28, Mycobacteriosis 39

Characteristics:

Orphanet epidemiological data:

58
mendelian susceptibility to mycobacterial diseases due to complete ifngammar2 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;
autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial ifngammar2 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in early childhood
patients may develop disseminated disease after bcg vaccination


HPO:

31
immunodeficiency 28:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0111995
OMIM® 57 614889
OMIM Phenotypic Series 57 PS300755
ICD10 via Orphanet 33 D84.8
SNOMED-CT via HPO 68 234532001 258211005
UMLS 70 C4013947

Summaries for Immunodeficiency 28

UniProtKB/Swiss-Prot : 72 Immunodeficiency 28: A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD28 is an autosomal recessive disease that manifests early in life, with severe, often fatal, infection.

MalaCards based summary : Immunodeficiency 28, also known as ifngr2 deficiency, is related to immunodeficiency 27a and beta-lactam allergy. An important gene associated with Immunodeficiency 28 is IFNGR2 (Interferon Gamma Receptor 2), and among its related pathways/superpathways are TGF-Beta Pathway and Cytokine Signaling in Immune system. Related phenotypes are immunodeficiency and recurrent mycobacterial infections

Disease Ontology : 12 A primary immunodeficiency disease characterized by increased susceptibility to mycobacterial disease, high levels of IFNG in the plasma, and absence of cellular response to IFNG that has material basis in homozygous or compound heterozygous mutation in IFNGR2 on chromosome 21q22.11.

OMIM® : 57 IMD28 is caused by autosomal recessive (AR) IFNGR2 deficiency, a rare molecular cause of susceptibility to mycobacterial disease. The clinical presentation of complete AR IFNGR2 deficiency resembles that of complete IFNGR1 deficiency (IMD27A; 209950). The disease manifests early in life, with severe, often fatal, infection. The most commonly encountered pathogens include M. bovis bacillus Calmette-Guerin (BCG), M. avium, and M. fortuitum. Complete AR IFNGR2 deficiency is characterized by an undetectable cellular response to interferon-gamma (IFNG; 147570). There is also a rare, partial form of AR IFNGR2 deficiency, reported in 1 child, who retained a residual cellular response to IFNG and presented with a relatively mild infection by M. bovis BCG and M. abscessus (review by Al-Muhsen and Casanova, 2008). (614889) (Updated 05-Apr-2021)

Related Diseases for Immunodeficiency 28

Graphical network of the top 20 diseases related to Immunodeficiency 28:



Diseases related to Immunodeficiency 28

Symptoms & Phenotypes for Immunodeficiency 28

Human phenotypes related to Immunodeficiency 28:

31
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 31 HP:0002721
2 recurrent mycobacterial infections 31 HP:0011274

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Immunology:
increased susceptibility to mycobacterial infections
poor or absent response to gamma-interferon

Clinical features from OMIM®:

614889 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Immunodeficiency 28 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased HPV18 LCR reporter activity GR00197-A-1 9.02 IL12RB1 SPPL2A TMEM50B
2 Increased HPV18 LCR reporter activity GR00197-A-3 9.02 TMEM50B
3 Increased HPV18 LCR reporter activity GR00197-A-4 9.02 TMEM50B

Drugs & Therapeutics for Immunodeficiency 28

Search Clinical Trials , NIH Clinical Center for Immunodeficiency 28

Genetic Tests for Immunodeficiency 28

Genetic tests related to Immunodeficiency 28:

# Genetic test Affiliating Genes
1 Immunodeficiency 28 29 IFNGR2

Anatomical Context for Immunodeficiency 28

Publications for Immunodeficiency 28

Articles related to Immunodeficiency 28:

# Title Authors PMID Year
1
A purely quantitative form of partial recessive IFN-γR2 deficiency caused by mutations of the initiation or second codon. 57 6
31222290 2018
2
Complementation of a pathogenic IFNGR2 misfolding mutation with modifiers of N-glycosylation. 57 6
18625743 2008
3
Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations. 57 6
15924140 2005
4
Structure of the IFNγ receptor complex guides design of biased agonists. 6
30814731 2019
5
The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. 57
19084105 2008
6
High levels of interferon gamma in the plasma of children with complete interferon gamma receptor deficiency. 57
11335769 2001
7
Mutation in the signal-transducing chain of the interferon-gamma receptor and susceptibility to mycobacterial infection. 6
9616207 1998
8
Clinical indications for intravenous immunoglobulin utilization in a tertiary medical center: a 9-year retrospective study. 61
29193136 2018

Variations for Immunodeficiency 28

ClinVar genetic disease variations for Immunodeficiency 28:

6 (show top 50) (show all 62)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 IFNGR2 NM_001329128.1(IFNGR2):c.333_334AG[1] (p.Glu112fs) Microsatellite Pathogenic 14726 rs587776822 GRCh37: 21:34793856-34793857
GRCh38: 21:33421549-33421550
2 IFNGR2 NM_005534.3(IFNGR2):c.503C>A (p.Thr168Asn) SNV Pathogenic 14727 rs74315444 GRCh37: 21:34799281-34799281
GRCh38: 21:33426974-33426974
3 IFNGR2 NM_005534.3(IFNGR2):c.663_689del (p.Phe224_Ile232del) Deletion Pathogenic 14728 rs587776823 GRCh37: 21:34804582-34804608
GRCh38: 21:33432275-33432301
4 IFNGR2 NM_005534.3(IFNGR2):c.382_387dup (p.Thr128_Met129dup) Duplication Pathogenic 37286 rs398122890 GRCh37: 21:34793959-34793960
GRCh38: 21:33421652-33421653
5 IFNGR2 NM_005534.4(IFNGR2):c.503_504del (p.Thr168fs) Deletion Pathogenic 949584 GRCh37: 21:34799281-34799282
GRCh38: 21:33426974-33426975
6 IFNGR2 NM_005534.4(IFNGR2):c.4del (p.Arg2fs) Deletion Pathogenic 987750 GRCh37: 21:34775853-34775853
GRCh38: 21:33403547-33403547
7 IFNGR2 NM_005534.4(IFNGR2):c.1A>G (p.Met1Val) SNV Pathogenic 987732 GRCh37: 21:34775850-34775850
GRCh38: 21:33403544-33403544
8 IFNGR2 NM_005534.3(IFNGR2):c.708A>T (p.Glu236Asp) SNV Conflicting interpretations of pathogenicity 111250 rs121913212 GRCh37: 21:34804630-34804630
GRCh38: 21:33432323-33432323
9 IFNGR2 , TMEM50B NM_005534.4(IFNGR2):c.879+4C>T SNV Uncertain significance 840030 GRCh37: 21:34805182-34805182
GRCh38: 21:33432875-33432875
10 IFNGR2 , TMEM50B NM_005534.4(IFNGR2):c.1006A>G (p.Thr336Ala) SNV Uncertain significance 842557 GRCh37: 21:34809261-34809261
GRCh38: 21:33436954-33436954
11 IFNGR2 NM_005534.4(IFNGR2):c.48CGC[6] (p.Ala22dup) Microsatellite Uncertain significance 939013 GRCh37: 21:34775896-34775897
GRCh38: 21:33403590-33403591
12 IFNGR2 NM_005534.4(IFNGR2):c.319A>G (p.Met107Val) SNV Uncertain significance 941744 GRCh37: 21:34793899-34793899
GRCh38: 21:33421592-33421592
13 IFNGR2 NM_005534.3(IFNGR2):c.308C>T (p.Ala103Val) SNV Uncertain significance 576275 rs139212989 GRCh37: 21:34793888-34793888
GRCh38: 21:33421581-33421581
14 IFNGR2 , TMEM50B NM_005534.3(IFNGR2):c.764C>T (p.Thr255Ile) SNV Uncertain significance 640908 rs373582182 GRCh37: 21:34805063-34805063
GRCh38: 21:33432756-33432756
15 IFNGR2 , TMEM50B NM_005534.4(IFNGR2):c.949T>C (p.Trp317Arg) SNV Uncertain significance 840029 GRCh37: 21:34809204-34809204
GRCh38: 21:33436897-33436897
16 IFNGR2 , TMEM50B NM_005534.3(IFNGR2):c.889G>A (p.Asp297Asn) SNV Uncertain significance 111259 rs121913219 GRCh37: 21:34809144-34809144
GRCh38: 21:33436837-33436837
17 IFNGR2 NM_005534.4(IFNGR2):c.20_31dup (p.Leu11_Leu12insArgSerLeuLeu) Duplication Uncertain significance 952636 GRCh37: 21:34775868-34775869
GRCh38: 21:33403562-33403563
18 IFNGR2 NM_005534.3(IFNGR2):c.65C>T (p.Ala22Val) SNV Uncertain significance 474969 rs1555878402 GRCh37: 21:34775914-34775914
GRCh38: 21:33403608-33403608
19 IFNGR2 NM_001329128.1(IFNGR2):c.48_50CGC[1] (p.Ala19_Ala22del) Microsatellite Uncertain significance 541801 rs765468464 GRCh37: 21:34775897-34775908
GRCh38: 21:33403591-33403602
20 IFNGR2 NM_005534.3(IFNGR2):c.514T>A (p.Phe172Ile) SNV Uncertain significance 541802 rs375419913 GRCh37: 21:34799292-34799292
GRCh38: 21:33426985-33426985
21 overlap with 4 genes NC_000021.8:g.(?_34638751)_(34809289_?)dup Duplication Uncertain significance 541805 GRCh37: 21:34638751-34809289
GRCh38:
22 IFNGR2 , TMEM50B NM_005534.3(IFNGR2):c.780G>A (p.Ser260=) SNV Uncertain significance 569520 rs121913217 GRCh37: 21:34805079-34805079
GRCh38: 21:33432772-33432772
23 IFNGR2 , TMEM50B NM_005534.3(IFNGR2):c.940G>A (p.Asp314Asn) SNV Uncertain significance 582786 rs369529404 GRCh37: 21:34809195-34809195
GRCh38: 21:33436888-33436888
24 IFNGR2 NM_005534.3(IFNGR2):c.510G>A (p.Thr170=) SNV Uncertain significance 111247 rs121913209 GRCh37: 21:34799288-34799288
GRCh38: 21:33426981-33426981
25 IFNGR2 and overlap with 1 gene(s) NC_000021.8:g.(?_34799171)_(34809289_?)dup Duplication Uncertain significance 650195 GRCh37: 21:34799171-34809289
GRCh38: 21:33426864-33436982
26 IFNGR2 , TMEM50B NM_005534.3(IFNGR2):c.914C>T (p.Ala305Val) SNV Uncertain significance 662505 rs893539360 GRCh37: 21:34809169-34809169
GRCh38: 21:33436862-33436862
27 IFNGR2 , TMEM50B NM_005534.3(IFNGR2):c.1007C>G (p.Thr336Arg) SNV Uncertain significance 664258 rs763384272 GRCh37: 21:34809262-34809262
GRCh38: 21:33436955-33436955
28 IFNGR2 NM_005534.3(IFNGR2):c.115C>T (p.Arg39Cys) SNV Uncertain significance 665306 rs572786148 GRCh37: 21:34787236-34787236
GRCh38: 21:33414929-33414929
29 IFNGR2 NM_005534.3(IFNGR2):c.56C>T (p.Ala19Val) SNV Uncertain significance 666003 rs956427420 GRCh37: 21:34775905-34775905
GRCh38: 21:33403599-33403599
30 IFNGR2 , TMEM50B NM_005534.4(IFNGR2):c.788C>T (p.Ala263Val) SNV Uncertain significance 998754 GRCh37: 21:34805087-34805087
GRCh38: 21:33432780-33432780
31 IFNGR2 NM_005534.4(IFNGR2):c.48CGC[3] (p.Ala21_Ala22del) Microsatellite Uncertain significance 1000970 GRCh37: 21:34775897-34775902
GRCh38: 21:33403591-33403596
32 IFNGR2 NM_005534.4(IFNGR2):c.406C>T (p.Arg136Trp) SNV Uncertain significance 1002548 GRCh37: 21:34793986-34793986
GRCh38: 21:33421679-33421679
33 IFNGR2 NM_005534.4(IFNGR2):c.451G>A (p.Gly151Arg) SNV Uncertain significance 1008942 GRCh37: 21:34799229-34799229
GRCh38: 21:33426922-33426922
34 IFNGR2 , TMEM50B NM_005534.4(IFNGR2):c.977C>T (p.Pro326Leu) SNV Uncertain significance 960830 GRCh37: 21:34809232-34809232
GRCh38: 21:33436925-33436925
35 IFNGR2 NM_005534.4(IFNGR2):c.116G>A (p.Arg39His) SNV Uncertain significance 1022655 GRCh37: 21:34787237-34787237
GRCh38: 21:33414930-33414930
36 IFNGR2 and overlap with 1 gene(s) NC_000021.8:g.(?_34799171)_(34809289_?)dup Duplication Uncertain significance 1023284 GRCh37: 21:34799171-34809289
GRCh38:
37 IFNGR2 NM_005534.3(IFNGR2):c.37C>T (p.Leu13Phe) SNV Uncertain significance 474968 rs1012938610 GRCh37: 21:34775886-34775886
GRCh38: 21:33403580-33403580
38 IFNGR2 NM_005534.3(IFNGR2):c.616A>G (p.Arg206Gly) SNV Uncertain significance 566491 rs147894635 GRCh37: 21:34804538-34804538
GRCh38: 21:33432231-33432231
39 IFNGR2 NM_005534.3(IFNGR2):c.58G>A (p.Ala20Thr) SNV Uncertain significance 582069 rs1176465152 GRCh37: 21:34775907-34775907
GRCh38: 21:33403601-33403601
40 IFNGR2 NM_005534.3(IFNGR2):c.532C>T (p.His178Tyr) SNV Uncertain significance 654567 rs769963583 GRCh37: 21:34799310-34799310
GRCh38: 21:33427003-33427003
41 IFNGR2 NM_005534.4(IFNGR2):c.277G>C (p.Glu93Gln) SNV Uncertain significance 860027 GRCh37: 21:34793857-34793857
GRCh38: 21:33421550-33421550
42 IFNGR2 NM_005534.4(IFNGR2):c.53C>T (p.Ala18Val) SNV Uncertain significance 863856 GRCh37: 21:34775902-34775902
GRCh38: 21:33403596-33403596
43 IFNGR2 NM_005534.4(IFNGR2):c.83C>T (p.Ser28Phe) SNV Uncertain significance 943609 GRCh37: 21:34787204-34787204
GRCh38: 21:33414897-33414897
44 IFNGR2 NM_001329128.1(IFNGR2):c.722A>T (p.Asn241Ile) SNV Uncertain significance 636564 rs201843430 GRCh37: 21:34804587-34804587
GRCh38: 21:33432280-33432280
45 IFNGR2 NM_005534.4(IFNGR2):c.610C>T (p.Pro204Ser) SNV Uncertain significance 1035663 GRCh37: 21:34804532-34804532
GRCh38: 21:33432225-33432225
46 IFNGR2 NM_005534.4(IFNGR2):c.232G>A (p.Asp78Asn) SNV Uncertain significance 1036762 GRCh37: 21:34793812-34793812
GRCh38: 21:33421505-33421505
47 IFNGR2 NM_005534.4(IFNGR2):c.407G>A (p.Arg136Gln) SNV Uncertain significance 1037224 GRCh37: 21:34793987-34793987
GRCh38: 21:33421680-33421680
48 IFNGR2 , TMEM50B NM_005534.4(IFNGR2):c.990AGA[1] (p.Glu331del) Microsatellite Uncertain significance 1046008 GRCh37: 21:34809244-34809246
GRCh38: 21:33436937-33436939
49 IFNGR2 NM_005534.3(IFNGR2):c.206+8G>A SNV Likely benign 541804 rs766931525 GRCh37: 21:34787335-34787335
GRCh38: 21:33415028-33415028
50 IFNGR2 , TMEM50B NM_005534.3(IFNGR2):c.756C>T (p.Ser252=) SNV Likely benign 717050 rs186369364 GRCh37: 21:34805055-34805055
GRCh38: 21:33432748-33432748

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 28:

72
# Symbol AA change Variation ID SNP ID
1 IFNGR2 p.Thr168Asn VAR_023281 rs74315444
2 IFNGR2 p.Arg114Cys VAR_075305 rs124350607
3 IFNGR2 p.Ser124Phe VAR_075306
4 IFNGR2 p.Gly141Arg VAR_075307 rs119609472
5 IFNGR2 p.Gly227Arg VAR_075308

Expression for Immunodeficiency 28

Search GEO for disease gene expression data for Immunodeficiency 28.

Pathways for Immunodeficiency 28

Pathways related to Immunodeficiency 28 according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.11 IL12RB1 IFNGR2 IFNGR1 IFNAR1
2
Show member pathways
12.95 IL12RB1 IFNGR2 IFNGR1 IFNAR1
3
Show member pathways
12.44 IFNGR2 IFNGR1 IFNAR1
4 12.42 IFNGR2 IFNGR1 IFNAR1
5 12.39 IL12RB1 IFNGR2 IFNGR1 IFNAR1
6
Show member pathways
12.21 IL12RB1 IFNGR2 IFNGR1
7
Show member pathways
12.14 IFNGR2 IFNGR1 IFNAR1
8
Show member pathways
12.08 IFNGR2 IFNGR1 IFNAR1
9
Show member pathways
12.01 IL12RB1 IFNGR2 IFNGR1 IFNAR1
10
Show member pathways
11.81 IFNGR2 IFNGR1 IFNAR1
11 11.6 IFNGR2 IFNGR1
12 11.6 IFNGR2 IFNGR1 IFNAR1
13 11.39 IFNGR2 IFNGR1 IFNAR1
14
Show member pathways
11.32 IL12RB1 IFNGR2 IFNGR1 IFNAR1
15
Show member pathways
11.23 IFNGR2 IFNGR1
16 11.18 IFNGR2 IFNGR1
17 11.02 IFNGR2 IFNGR1
18
Show member pathways
11.01 IL12RB1 IFNGR2 IFNGR1

GO Terms for Immunodeficiency 28

Cellular components related to Immunodeficiency 28 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.43 TMEM50B SPPL2A IL12RB1 IFNGR2 IFNGR1 IFNAR1
2 late endosome GO:0005770 9.16 SPPL2A IFNAR1
3 plasma membrane GO:0005886 9.1 TMEM50B SPPL2A IL12RB1 IFNGR2 IFNGR1 IFNAR1

Biological processes related to Immunodeficiency 28 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 interferon-gamma-mediated signaling pathway GO:0060333 9.32 IFNGR2 IFNGR1
2 microglial cell activation GO:0001774 9.26 IFNGR2 IFNGR1
3 regulation of interferon-gamma-mediated signaling pathway GO:0060334 9.16 IFNGR2 IFNGR1
4 response to virus GO:0009615 9.13 IFNGR2 IFNGR1 IFNAR1
5 cytokine-mediated signaling pathway GO:0019221 8.92 IL12RB1 IFNGR2 IFNGR1 IFNAR1

Molecular functions related to Immunodeficiency 28 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine binding GO:0019955 9.16 IL12RB1 IFNGR1
2 interferon-gamma receptor activity GO:0004906 8.96 IFNGR2 IFNGR1
3 cytokine receptor activity GO:0004896 8.92 IL12RB1 IFNGR2 IFNGR1 IFNAR1

Sources for Immunodeficiency 28

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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