CVID1
MCID: IMM038
MIFTS: 38

Immunodeficiency, Common Variable, 1 (CVID1)

Categories: Cardiovascular diseases, Genetic diseases, Immune diseases, Infectious diseases

Aliases & Classifications for Immunodeficiency, Common Variable, 1

MalaCards integrated aliases for Immunodeficiency, Common Variable, 1:

Name: Immunodeficiency, Common Variable, 1 57 72 13 70
Antibody Deficiency Due to Icos Defect 57 72
Common Variable Immunodeficiency 1 29 6
Icos Deficiency 72 54
Cvid1 57 72
Immunodeficiency, Variable, Common, Type 1 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable age at onset, ranging from 18 months to 27 years


HPO:

31
immunodeficiency, common variable, 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Immunodeficiency, Common Variable, 1

OMIM® : 57 Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous group of disorders characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections, and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells are usually in the normal range, but can be low. Most individuals with CVID have onset of infections after age 10 years. CVID represents the most common form of primary immunodeficiency disorders and is the most common form of primary antibody deficiency. Approximately 10 to 20% of patients with a diagnosis of CVID have a family history of the disorder (reviews by Chapel et al., 2008, Conley et al., 2009, and Yong et al., 2009). (607594) (Updated 20-May-2021)

MalaCards based summary : Immunodeficiency, Common Variable, 1, also known as antibody deficiency due to icos defect, is related to common variable immunodeficiency and combined immunodeficiency, and has symptoms including diarrhea An important gene associated with Immunodeficiency, Common Variable, 1 is ICOS (Inducible T Cell Costimulator), and among its related pathways/superpathways are Allograft rejection and RANK Signaling in Osteoclasts. Affiliated tissues include b cells, t cells and whole blood, and related phenotypes are neutropenia in presence of anti-neutropil antibodies and splenomegaly

UniProtKB/Swiss-Prot : 72 Immunodeficiency, common variable, 1: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.

Related Diseases for Immunodeficiency, Common Variable, 1

Graphical network of the top 20 diseases related to Immunodeficiency, Common Variable, 1:



Diseases related to Immunodeficiency, Common Variable, 1

Symptoms & Phenotypes for Immunodeficiency, Common Variable, 1

Human phenotypes related to Immunodeficiency, Common Variable, 1:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 neutropenia in presence of anti-neutropil antibodies 31 occasional (7.5%) HP:0001904
2 splenomegaly 31 HP:0001744
3 hepatomegaly 31 HP:0002240
4 immunodeficiency 31 HP:0002721
5 recurrent otitis media 31 HP:0000403
6 impaired t cell function 31 HP:0005435
7 conjunctivitis 31 HP:0000509
8 recurrent pneumonia 31 HP:0006532
9 pneumonia 31 HP:0002090
10 diarrhea 31 HP:0002014
11 lymphadenopathy 31 HP:0002716
12 bronchiectasis 31 HP:0002110
13 decreased circulating iga level 31 HP:0002720
14 decreased circulating igg level 31 HP:0004315
15 decreased circulating total igm 31 HP:0002850
16 recurrent bronchitis 31 HP:0002837
17 recurrent bacterial infections 31 HP:0002718
18 recurrent sinusitis 31 HP:0011108
19 b lymphocytopenia 31 HP:0010976

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Abdomen Spleen:
splenomegaly

Head And Neck Eyes:
conjunctivitis

Immunology:
lymphadenopathy
recurrent bacterial infections
hypogammaglobulinemia
defective antibody production
normal numbers of t cells
more
Head And Neck Head:
sinusitis, recurrent

Respiratory Lung:
pneumonia, recurrent

Abdomen Liver:
hepatomegaly

Abdomen Gastrointestinal:
diarrhea
enteritis, recurrent

Respiratory Airways:
bronchiectasis
bronchitis, recurrent

Head And Neck Ears:
otitis media, recurrent

Laboratory Abnormalities:
markedly reduced iga levels
markedly reduced igg levels
reduced igm levels

Clinical features from OMIM®:

607594 (Updated 20-May-2021)

UMLS symptoms related to Immunodeficiency, Common Variable, 1:


diarrhea

Drugs & Therapeutics for Immunodeficiency, Common Variable, 1

Search Clinical Trials , NIH Clinical Center for Immunodeficiency, Common Variable, 1

Genetic Tests for Immunodeficiency, Common Variable, 1

Genetic tests related to Immunodeficiency, Common Variable, 1:

# Genetic test Affiliating Genes
1 Common Variable Immunodeficiency 1 29 ICOS

Anatomical Context for Immunodeficiency, Common Variable, 1

MalaCards organs/tissues related to Immunodeficiency, Common Variable, 1:

40
B Cells, T Cells, Whole Blood, Nk Cells, Brain, Skin

Publications for Immunodeficiency, Common Variable, 1

Articles related to Immunodeficiency, Common Variable, 1:

(show top 50) (show all 52)
# Title Authors PMID Year
1
Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. 61 54 57 6
12577056 2003
2
ICOS deficiency in patients with common variable immunodeficiency. 57 6 61
15507387 2004
3
ICOS is critical for CD40-mediated antibody class switching. 6 57
11343122 2001
4
Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. 6 61
19380800 2009
5
The role of costimulation in antibody deficiencies: ICOS and common variable immunodeficiency. 61 57
19426217 2009
6
ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells. 61 57
16982935 2006
7
TACI mutations and impaired B-cell function in subjects with CVID and healthy heterozygotes. 6
23237420 2013
8
Sequence variants of the TNFRSF13B gene in Czech CVID and IgAD patients in the context of other populations. 6
22884984 2012
9
Functional analysis of transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) mutations associated with common variable immunodeficiency. 6
21419480 2011
10
Phenotypic and clinical heterogeneity associated with monoallelic TNFRSF13B-A181E mutations in common variable immunodeficiency. 6
20156508 2010
11
The murine equivalent of the A181E TACI mutation associated with common variable immunodeficiency severely impairs B-cell function. 6
19605846 2009
12
Role of TNFRSF13B variants in patients with common variable immunodeficiency. 6
19779048 2009
13
Primary B cell immunodeficiencies: comparisons and contrasts. 57
19302039 2009
14
Common variable immunodeficiency disorders: division into distinct clinical phenotypes. 57
18319398 2008
15
Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. 6
17392797 2007
16
TLR9 activation is defective in common variable immune deficiency. 57
16424230 2006
17
Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. 6
16007087 2005
18
TACI is mutant in common variable immunodeficiency and IgA deficiency. 6
16007086 2005
19
Impaired secretion of IL-10 by T cells from patients with common variable immunodeficiency--involvement of protein kinase A type I. 57
12759461 2003
20
ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells. 57
12207353 2002
21
Common variable immunodeficiency: clinical and immunological features of 248 patients. 57
10413651 1999
22
Defect in IgV gene somatic hypermutation in common variable immuno-deficiency syndrome. 57
9789054 1998
23
CD40 ligand expression is defective in a subset of patients with common variable immunodeficiency. 57
7508119 1994
24
Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. 57
8438047 1993
25
Kinetics of the spontaneously occurring common variable hypogammaglobulinemia: an analysis of two individuals with previously normal immunoglobulin levels. 57
2863024 1985
26
Idiopathic late-onset immunoglobulin deficiency. Clinical observations in 50 patients. 57
782241 1976
27
Heterogeneity of "acquired" or common variable agammaglobulinemia. 57
4545549 1974
28
Quantitative abnormalities of allotypic genes in families with primary immune deficiencies. 57
4625886 1972
29
Agammaglobulinaemia with B lymphocytes. Specific defect of plasma-cell differentiation. 57
4106608 1971
30
A genetic defect in "acquired" agammaglobulinemia. 57
5243929 1968
31
Paternal immunoglobulin abnormalities in congenital hypogammaglobulinemia. 57
4164115 1967
32
ACQUIRED AGAMMAGLOBULINAEMIA IN SIBLINGS. 57
14238063 1965
33
Inherited "acquired" hypogammaglobulinaemia. 57
13786420 1961
34
Molecular basis of common variable immunodeficiency. 54 61
16630927 2006
35
Rapid whole blood flow cytometric test to detect ICOS deficiency in patients with common variable immunodeficiency. 61 54
16757923 2006
36
ICOSL in host defense at epithelial barriers: lessons from ICOSLG deficiency. 61
33756276 2021
37
Expanding Clinical Phenotype and Novel Insights into the Pathogenesis of ICOS Deficiency. 61
31858365 2020
38
ICOS-deficient and ICOS YF mutant mice fail to control Toxoplasma gondii infection of the brain. 61
31978191 2020
39
Cutting Edge: ICOS-Deficient Regulatory T Cells Display Normal Induction of Il10 but Readily Downregulate Expression of Foxp3. 61
30642977 2019
40
ICOS deficiency hampers the homeostasis, development and function of NK cells. 61
31283790 2019
41
Inducible T-Cell Co-Stimulator Impacts Chronic Graft-Versus-Host Disease by Regulating Both Pathogenic and Regulatory T Cells. 61
29988391 2018
42
14 Years after Discovery: Clinical Follow-up on 15 Patients with Inducible Co-Stimulator Deficiency. 61
28861081 2017
43
Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis. 61
26399252 2015
44
ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection. 61
23319295 2013
45
Impact of inducible co-stimulatory molecule (ICOS) on T-cell responses and protection against Mycobacterium tuberculosis infection. 61
21337542 2011
46
Inducible costimulator ligand regulates bleomycin-induced lung and skin fibrosis in a mouse model independently of the inducible costimulator/inducible costimulator ligand pathway. 61
20191584 2010
47
ICOS deficiency results in exacerbated IL-17 mediated experimental autoimmune encephalomyelitis. 61
19291374 2009
48
CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo. 61
19646680 2009
49
TACI, isotype switching, CVID and IgAD. 61
17917015 2007
50
Role of inducible costimulator in the development of lupus in MRL/lpr mice. 61
16616645 2006

Variations for Immunodeficiency, Common Variable, 1

ClinVar genetic disease variations for Immunodeficiency, Common Variable, 1:

6 (show top 50) (show all 117)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ICOS ICOS, 1,815-BP DEL Deletion Pathogenic 5501 GRCh37:
GRCh38:
2 ICOS NM_012092.4(ICOS):c.181del (p.Ile61fs) Deletion Pathogenic 940397 GRCh37: 2:204820479-204820479
GRCh38: 2:203955756-203955756
3 NFKB2 NM_001322934.2(NFKB2):c.2564del (p.Lys855fs) Deletion Pathogenic 65386 rs397514331 GRCh37: 10:104161901-104161901
GRCh38: 10:102402144-102402144
4 ICOS NM_012092.3(ICOS):c.394+2T>C SNV Likely pathogenic 573877 rs1559035937 GRCh37: 2:204820696-204820696
GRCh38: 2:203955973-203955973
5 TNFRSF13B NM_012452.2(TNFRSF13B):c.542C>A (p.Ala181Glu) SNV Likely pathogenic 5303 rs72553883 GRCh37: 17:16843729-16843729
GRCh38: 17:16940415-16940415
6 ICOS NM_012092.3(ICOS):c.58+1G>A SNV Likely pathogenic 663980 rs757598952 GRCh37: 2:204801596-204801596
GRCh38: 2:203936873-203936873
7 ICOS NM_012092.3(ICOS):c.591G>A (p.Val197=) SNV Conflicting interpretations of pathogenicity 333737 rs55655222 GRCh37: 2:204824313-204824313
GRCh38: 2:203959590-203959590
8 ICOS NM_012092.3(ICOS):c.451G>C (p.Val151Leu) SNV Conflicting interpretations of pathogenicity 497910 rs76778263 GRCh37: 2:204821438-204821438
GRCh38: 2:203956715-203956715
9 ICOS NM_012092.4(ICOS):c.375A>G (p.Gly125=) SNV Conflicting interpretations of pathogenicity 784704 rs768500706 GRCh37: 2:204820675-204820675
GRCh38: 2:203955952-203955952
10 ICOS NM_012092.3(ICOS):c.58+9T>G SNV Conflicting interpretations of pathogenicity 333732 rs140049646 GRCh37: 2:204801604-204801604
GRCh38: 2:203936881-203936881
11 ICOS NM_012092.3(ICOS):c.*1854G>A SNV Uncertain significance 333761 rs140979765 GRCh37: 2:204826176-204826176
GRCh38: 2:203961453-203961453
12 ICOS NM_012092.3(ICOS):c.*1293T>C SNV Uncertain significance 333758 rs528769953 GRCh37: 2:204825615-204825615
GRCh38: 2:203960892-203960892
13 ICOS NM_012092.3(ICOS):c.*931A>G SNV Uncertain significance 333746 rs886055497 GRCh37: 2:204825253-204825253
GRCh38: 2:203960530-203960530
14 ICOS NM_012092.3(ICOS):c.*995C>T SNV Uncertain significance 333749 rs190590580 GRCh37: 2:204825317-204825317
GRCh38: 2:203960594-203960594
15 ICOS NM_012092.4(ICOS):c.128A>G (p.Lys43Arg) SNV Uncertain significance 960748 GRCh37: 2:204820428-204820428
GRCh38: 2:203955705-203955705
16 ICOS NM_012092.3(ICOS):c.597A>G (p.Leu199=) SNV Uncertain significance 333738 rs145698501 GRCh37: 2:204824319-204824319
GRCh38: 2:203959596-203959596
17 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.142G>C (p.Ala48Pro) SNV Uncertain significance 946878 GRCh37: 17:7452612-7452612
GRCh38: 17:7549295-7549295
18 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.245C>T (p.Ala82Val) SNV Uncertain significance 933662 GRCh37: 17:7453474-7453474
GRCh38: 17:7550157-7550157
19 ICOS NM_012092.4(ICOS):c.512C>A (p.Ser171Tyr) SNV Uncertain significance 936305 GRCh37: 2:204822532-204822532
GRCh38: 2:203957809-203957809
20 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.596C>T (p.Ala199Val) SNV Uncertain significance 938176 GRCh37: 17:7460513-7460513
GRCh38: 17:7557196-7557196
21 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.364G>A (p.Ala122Thr) SNV Uncertain significance 957771 GRCh37: 17:7454286-7454286
GRCh38: 17:7550969-7550969
22 overlap with 83 genes NC_000017.10:g.(?_6589506)_(8151374_?)dup Duplication Uncertain significance 831200 GRCh37: 17:6589506-8151374
GRCh38:
23 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.433C>T (p.Arg145Cys) SNV Uncertain significance 225690 rs540997935 GRCh37: 17:7460154-7460154
GRCh38: 17:7556837-7556837
24 ICOS NM_012092.4(ICOS):c.500del (p.Lys167fs) Deletion Uncertain significance 1052706 GRCh37: 2:204821482-204821482
GRCh38: 2:203956759-203956759
25 ICOS NM_012092.4(ICOS):c.376G>A (p.Gly126Arg) SNV Uncertain significance 1053379 GRCh37: 2:204820676-204820676
GRCh38: 2:203955953-203955953
26 ICOS NM_012092.4(ICOS):c.502-6_502-5insG Insertion Uncertain significance 1058053 GRCh37: 2:204822516-204822517
GRCh38: 2:203957793-203957794
27 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.38G>A (p.Arg13Gln) SNV Uncertain significance 1061548 GRCh37: 17:7452508-7452508
GRCh38: 17:7549191-7549191
28 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.296G>A (p.Arg99Gln) SNV Uncertain significance 1063721 GRCh37: 17:7454128-7454128
GRCh38: 17:7550811-7550811
29 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.43G>A (p.Glu15Lys) SNV Uncertain significance 526011 rs768061768 GRCh37: 17:7452513-7452513
GRCh38: 17:7549196-7549196
30 ICOS NM_012092.3(ICOS):c.589G>A (p.Val197Met) SNV Uncertain significance 666015 rs111644920 GRCh37: 2:204824311-204824311
GRCh38: 2:203959588-203959588
31 ICOS NM_012092.4(ICOS):c.586+3A>G SNV Uncertain significance 835162 GRCh37: 2:204822609-204822609
GRCh38: 2:203957886-203957886
32 ICOS NM_012092.4(ICOS):c.77C>A (p.Ala26Asp) SNV Uncertain significance 841396 GRCh37: 2:204820377-204820377
GRCh38: 2:203955654-203955654
33 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.469C>T (p.Arg157Trp) SNV Uncertain significance 945930 GRCh37: 17:7460190-7460190
GRCh38: 17:7556873-7556873
34 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.569G>C (p.Arg190Pro) SNV Uncertain significance 954481 GRCh37: 17:7460486-7460486
GRCh38: 17:7557169-7557169
35 TNFSF12 , TNFSF12-TNFSF13 NM_003809.3(TNFSF12):c.707C>T (p.Ala236Val) SNV Uncertain significance 969323 GRCh37: 17:7460624-7460624
GRCh38: 17:7557307-7557307
36 ICOS NM_012092.4(ICOS):c.271A>G (p.Ser91Gly) SNV Uncertain significance 969446 GRCh37: 2:204820571-204820571
GRCh38: 2:203955848-203955848
37 ICOS NM_012092.4(ICOS):c.495A>C (p.Thr165=) SNV Uncertain significance 895773 GRCh37: 2:204821482-204821482
GRCh38: 2:203956759-203956759
38 ICOS NM_012092.4(ICOS):c.*1137C>T SNV Uncertain significance 895843 GRCh37: 2:204825459-204825459
GRCh38: 2:203960736-203960736
39 ICOS NM_012092.4(ICOS):c.*1172G>A SNV Uncertain significance 895844 GRCh37: 2:204825494-204825494
GRCh38: 2:203960771-203960771
40 ICOS NM_012092.4(ICOS):c.*1269A>C SNV Uncertain significance 895845 GRCh37: 2:204825591-204825591
GRCh38: 2:203960868-203960868
41 ICOS NM_012092.4(ICOS):c.510A>G (p.Ser170=) SNV Uncertain significance 896052 GRCh37: 2:204822530-204822530
GRCh38: 2:203957807-203957807
42 ICOS NM_012092.4(ICOS):c.*73T>C SNV Uncertain significance 896053 GRCh37: 2:204824395-204824395
GRCh38: 2:203959672-203959672
43 ICOS NM_012092.4(ICOS):c.*1300C>T SNV Uncertain significance 896118 GRCh37: 2:204825622-204825622
GRCh38: 2:203960899-203960899
44 ICOS NM_012092.4(ICOS):c.*1416G>T SNV Uncertain significance 896119 GRCh37: 2:204825738-204825738
GRCh38: 2:203961015-203961015
45 ICOS NM_012092.4(ICOS):c.*1457A>G SNV Uncertain significance 896120 GRCh37: 2:204825779-204825779
GRCh38: 2:203961056-203961056
46 ICOS NM_012092.4(ICOS):c.*1869A>C SNV Uncertain significance 896121 GRCh37: 2:204826191-204826191
GRCh38: 2:203961468-203961468
47 ICOS NM_012092.4(ICOS):c.*399G>A SNV Uncertain significance 897638 GRCh37: 2:204824721-204824721
GRCh38: 2:203959998-203959998
48 ICOS NM_012092.4(ICOS):c.*474G>T SNV Uncertain significance 897639 GRCh37: 2:204824796-204824796
GRCh38: 2:203960073-203960073
49 ICOS NM_012092.4(ICOS):c.*512T>C SNV Uncertain significance 897640 GRCh37: 2:204824834-204824834
GRCh38: 2:203960111-203960111
50 ICOS NM_012092.4(ICOS):c.*594C>T SNV Uncertain significance 897641 GRCh37: 2:204824916-204824916
GRCh38: 2:203960193-203960193

Expression for Immunodeficiency, Common Variable, 1

Search GEO for disease gene expression data for Immunodeficiency, Common Variable, 1.

Pathways for Immunodeficiency, Common Variable, 1

Pathways related to Immunodeficiency, Common Variable, 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.15 TNFRSF13B ICOS
2
Show member pathways
11.95 TNFRSF13B NFKB2
3
Show member pathways
11.88 NFKB2 ICOS
4 11.77 NFKB2 ICOS
5
Show member pathways
11.02 TNFRSF13B NFKB2
6 10.78 TNFRSF13B ICOS
7 10.2 TNFRSF13B ICOS

GO Terms for Immunodeficiency, Common Variable, 1

Sources for Immunodeficiency, Common Variable, 1

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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