CVID12
MCID: IMM241
MIFTS: 25

Immunodeficiency, Common Variable, 12, with Autoimmunity (CVID12)

Categories: Genetic diseases, Immune diseases

Aliases & Classifications for Immunodeficiency, Common Variable, 12, with Autoimmunity

MalaCards integrated aliases for Immunodeficiency, Common Variable, 12, with Autoimmunity:

Name: Immunodeficiency, Common Variable, 12, with Autoimmunity 57
Immunodeficiency, Common Variable, 12 57 72 29 6
Nfkb1 Deficiency 57 72
Cvid12 57 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
age-dependent penetrance
variable severity
highly variable phenotype
variable age at onset (range childhood to adult)
incomplete penetrance (about 60%)

Inheritance:
autosomal dominant


HPO:

31
immunodeficiency, common variable, 12, with autoimmunity:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


Classifications:



External Ids:

OMIM® 57 616576
OMIM Phenotypic Series 57 PS607594
MeSH 44 D017074

Summaries for Immunodeficiency, Common Variable, 12, with Autoimmunity

OMIM® : 57 Common variable immunodeficiency-12 with autoimmunity (CVID12) is an autosomal dominant complex immunologic disorder with multisystem involvement. CVID12 is mainly a primary immunodeficiency characterized by recurrent infections and associated with hypogammaglobulinemia. Notably, about half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. A smaller percentage of affected individuals (less than 20%) develop cancer, most commonly solid tumors, including lymphoma. Age at onset and disease severity are highly variable, even within the same family. There is also incomplete penetrance, such that mutation carriers may be asymptomatic, even if they have hypogammaglobulinemia. The gene involved, NFKB1, encodes a transcription factor that regulates the expression of target genes involved in the immune system, thus defining the phenotype as a disorder of immune dysregulation (summary by Fliegauf et al., 2015; Lorenzini et al., 2020). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594). (616576) (Updated 20-May-2021)

MalaCards based summary : Immunodeficiency, Common Variable, 12, with Autoimmunity, is also known as immunodeficiency, common variable, 12. An important gene associated with Immunodeficiency, Common Variable, 12, with Autoimmunity is NFKB1 (Nuclear Factor Kappa B Subunit 1). Affiliated tissues include nk cells, t cells and b cells, and related phenotypes are alopecia and thrombocytopenia

UniProtKB/Swiss-Prot : 72 Immunodeficiency, common variable, 12: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen.

Related Diseases for Immunodeficiency, Common Variable, 12, with Autoimmunity

Symptoms & Phenotypes for Immunodeficiency, Common Variable, 12, with Autoimmunity

Human phenotypes related to Immunodeficiency, Common Variable, 12, with Autoimmunity:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 alopecia 31 occasional (7.5%) HP:0001596
2 thrombocytopenia 31 occasional (7.5%) HP:0001873
3 hemolytic anemia 31 occasional (7.5%) HP:0001878
4 immunodeficiency 31 HP:0002721
5 recurrent sinopulmonary infections 31 HP:0005425
6 recurrent skin infections 31 HP:0001581
7 chronic pulmonary obstruction 31 HP:0006510
8 decreased circulating antibody level 31 HP:0004313

Symptoms via clinical synopsis from OMIM®:

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

Skeletal:
arthritis

Immunology:
immunodeficiency
thrombocytopenia
hemolytic anemia
lymphadenopathy
immune dysregulation
more
Respiratory:
recurrent sinopulmonary infections

Skin Nails Hair Skin:
recurrent skin infections

Abdomen Gastrointestinal:
pernicious anemia
gastrointestinal infections
chronic enteropathy
lymphocytic colitis

Neoplasia:
increased risk for solid malignant tumors
increased risk for lymphoma

Abdomen Liver:
hepatomegaly
hepatitis
hepatopathy

Endocrine Features:
type i diabetes mellitus
thyroiditis
addison disease

Cardiovascular Vascular:
vasculitis

Respiratory Lung:
bronchiectasis
interstitial lymphocytic infiltration

Head And Neck Mouth:
aphthous ulcers

Skin Nails Hair Hair:
alopecia (in some patients)

Clinical features from OMIM®:

616576 (Updated 20-May-2021)

Drugs & Therapeutics for Immunodeficiency, Common Variable, 12, with Autoimmunity

Search Clinical Trials , NIH Clinical Center for Immunodeficiency, Common Variable, 12, with Autoimmunity

Genetic Tests for Immunodeficiency, Common Variable, 12, with Autoimmunity

Genetic tests related to Immunodeficiency, Common Variable, 12, with Autoimmunity:

# Genetic test Affiliating Genes
1 Immunodeficiency, Common Variable, 12 29 NFKB1

Anatomical Context for Immunodeficiency, Common Variable, 12, with Autoimmunity

MalaCards organs/tissues related to Immunodeficiency, Common Variable, 12, with Autoimmunity:

40
Nk Cells, T Cells, B Cells

Publications for Immunodeficiency, Common Variable, 12, with Autoimmunity

Articles related to Immunodeficiency, Common Variable, 12, with Autoimmunity:

# Title Authors PMID Year
1
Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations. 57 6
32278790 2020
2
Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans. 57 6
29477724 2018
3
Specific antibody deficiency and autoinflammatory disease extend the clinical and immunological spectrum of heterozygous NFKB1 loss-of-function mutations in humans. 6 57
27365489 2016
4
Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency. 6 57
26279205 2015
5
Linkage of autosomal-dominant common variable immunodeficiency to chromosome 4q. 6 57
16639407 2006
6
Common variable immunodeficiency (CVID) in a family: an autosomal dominant mode of inheritance. 6 57
11583829 2001
7
Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics. 6
29077208 2018
8
Th1-skewed profile and excessive production of proinflammatory cytokines in a NFKB1-deficient patient with CVID and severe gastrointestinal manifestations. 61
30063981 2018
9
The Expanding Spectrum of NFkB1 Deficiency. 61
27338826 2016
10
Complex regulation of acute and chronic neuroinflammatory responses in mouse models deficient for nuclear factor kappa B p50 subunit. 61
24345324 2014

Variations for Immunodeficiency, Common Variable, 12, with Autoimmunity

ClinVar genetic disease variations for Immunodeficiency, Common Variable, 12, with Autoimmunity:

6 (show all 25)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NFKB1 NM_003998.4(NFKB1):c.730+4A>G SNV Pathogenic 210056 rs869320688 GRCh37: 4:103500200-103500200
GRCh38: 4:102579043-102579043
2 NFKB1 NM_003998.4(NFKB1):c.835+2T>G SNV Pathogenic 210057 rs869320689 GRCh37: 4:103501798-103501798
GRCh38: 4:102580641-102580641
3 NFKB1 NM_003998.4(NFKB1):c.465dup (p.Ala156fs) Duplication Pathogenic 210058 rs869320754 GRCh37: 4:103498088-103498089
GRCh38: 4:102576931-102576932
4 NFKB1 NM_003998.4(NFKB1):c.159+1G>A SNV Pathogenic 976031 GRCh37: 4:103455043-103455043
GRCh38: 4:102533886-102533886
5 NFKB1 NM_003998.4(NFKB1):c.522_525dup (p.Leu176Ter) Duplication Pathogenic 982698 GRCh37: 4:103498145-103498146
GRCh38: 4:102576988-102576989
6 NFKB1 NM_003998.4(NFKB1):c.418_427del (p.Leu140fs) Deletion Pathogenic 1027409 GRCh37: 4:103498041-103498050
GRCh38: 4:102576884-102576893
7 NFKB1 NM_003998.4(NFKB1):c.139del (p.Ile47fs) Deletion Pathogenic 1064676 GRCh37: 4:103455020-103455020
GRCh38: 4:102533863-102533863
8 NFKB1 NM_003998.4(NFKB1):c.169C>T (p.Arg57Cys) SNV Pathogenic 1058857 GRCh37: 4:103459024-103459024
GRCh38: 4:102537867-102537867
9 NFKB1 NM_003998.4(NFKB1):c.469C>T (p.Arg157Ter) SNV Pathogenic 1064678 GRCh37: 4:103498094-103498094
GRCh38: 4:102576937-102576937
10 NFKB1 NM_003998.4(NFKB1):c.260T>G (p.Ile87Ser) SNV Pathogenic 827719 rs1578771120 GRCh37: 4:103488145-103488145
GRCh38: 4:102566988-102566988
11 NFKB1 NM_003998.4(NFKB1):c.1012del (p.Ser338fs) Deletion Pathogenic 1064682 GRCh37: 4:103505923-103505923
GRCh38: 4:102584766-102584766
12 NFKB1 NM_003998.4(NFKB1):c.1539_1543del (p.His513fs) Deletion Pathogenic 827724 rs1578811073 GRCh37: 4:103518718-103518722
GRCh38: 4:102597561-102597565
13 NFKB1 NM_003998.4(NFKB1):c.850C>T (p.Arg284Ter) SNV Pathogenic 827726 rs1578793312 GRCh37: 4:103504037-103504037
GRCh38: 4:102582880-102582880
14 NFKB1 NM_003998.4(NFKB1):c.904dup (p.Ser302fs) Duplication Pathogenic/Likely pathogenic 430907 rs773694113 GRCh37: 4:103504086-103504087
GRCh38: 4:102582929-102582930
15 NFKB1 NM_003998.4(NFKB1):c.317dup (p.Asn106fs) Duplication Likely pathogenic 623198 rs1560679469 GRCh37: 4:103488196-103488197
GRCh38: 4:102567039-102567040
16 NFKB1 NM_003998.4(NFKB1):c.1752+1G>A SNV Likely pathogenic 623199 rs1560711146 GRCh37: 4:103522167-103522167
GRCh38: 4:102601010-102601010
17 NFKB1 NM_003998.4(NFKB1):c.2671del (p.Ala891fs) Deletion Likely pathogenic 983472 GRCh37: 4:103534659-103534659
GRCh38: 4:102613502-102613502
18 NFKBID NM_139239.2(NFKBID):c.506G>T (p.Arg169Leu) SNV Uncertain significance 973654 GRCh37: 19:36386982-36386982
GRCh38: 19:35896080-35896080
19 NFKBID NM_139239.2(NFKBID):c.773C>T (p.Pro258Leu) SNV Uncertain significance 973655 GRCh37: 19:36380907-36380907
GRCh38: 19:35890005-35890005
20 NFKB1 NM_003998.4(NFKB1):c.2027C>T (p.Ala676Val) SNV Uncertain significance 1029786 GRCh37: 4:103528379-103528379
GRCh38: 4:102607222-102607222
21 NFKB1 NM_003998.4(NFKB1):c.671G>A (p.Ser224Asn) SNV Uncertain significance 1029787 GRCh37: 4:103500137-103500137
GRCh38: 4:102578980-102578980
22 NFKB1 NM_003998.4(NFKB1):c.1845G>T (p.Leu615Phe) SNV Likely benign 709895 rs149211506 GRCh37: 4:103527745-103527745
GRCh38: 4:102606588-102606588
23 NFKB1 NM_003998.4(NFKB1):c.1755G>A (p.Thr585=) SNV Benign 776003 rs4648093 GRCh37: 4:103527655-103527655
GRCh38: 4:102606498-102606498
24 NFKB1 NM_003998.4(NFKB1):c.1050C>T (p.Tyr350=) SNV Benign 993341 GRCh37: 4:103505961-103505961
GRCh38: 4:102584804-102584804
25 NFKB1 NM_003998.4(NFKB1):c.1519A>G (p.Met507Val) SNV Benign 445400 rs4648072 GRCh37: 4:103518700-103518700
GRCh38: 4:102597543-102597543

Expression for Immunodeficiency, Common Variable, 12, with Autoimmunity

Search GEO for disease gene expression data for Immunodeficiency, Common Variable, 12, with Autoimmunity.

Pathways for Immunodeficiency, Common Variable, 12, with Autoimmunity

GO Terms for Immunodeficiency, Common Variable, 12, with Autoimmunity

Sources for Immunodeficiency, Common Variable, 12, with Autoimmunity

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
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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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