MCID: C3D001
MIFTS: 48

C3 Deficiency

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

Aliases & Classifications for C3 Deficiency

MalaCards integrated aliases for C3 Deficiency:

Name: C3 Deficiency 54 12 56 29 13 69
Complement Component 3 Deficiency 12 56 71 14
Immune System Diseases 42 69
Complement Component 3 Deficiency, Autosomal Recessive 29
Complement Component 3 Deficiency Autosomal Recessive 71
C3 Deficiency, Autosomal Recessive 24
C3 Deficiency Autosomal Recessive 71
Complement Component-3 13
C3d 71

Characteristics:

Orphanet epidemiological data:

56
complement component 3 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

54
Miscellaneous:
onset in infancy or early childhood

Inheritance:
autosomal recessive


HPO:

32
c3 deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare immunological diseases


External Ids:

OMIM 54 613779
Disease Ontology 12 DOID:8354
NCIt 47 C9468
Orphanet 56 ORPHA280133
UMLS via Orphanet 70 C3151071
ICD10 via Orphanet 34 D84.1
MedGen 40 C3151071
MeSH 42 D007154
UMLS 69 C1332655

Summaries for C3 Deficiency

OMIM : 54
The main clinical manifestation of primary C3 deficiency is childhood-onset of recurrent bacterial infections, mainly caused by gram-negative bacteria, such as Neisseria meningitidis, Enterobacter aerogenes, Haemophilus influenzae, and Escherichia coli; infections with gram-positive bacteria also occur. Infections in the upper and lower respiratory tract, including pneumonia, episodes of sinusitis, tonsillitis, and otitis, are the most frequent consequence of the C3 deficiency. Approximately 26% of patients with C3 deficiency develop immune complex-mediated autoimmune diseases resembling systemic lupus erythematosus (see 152700), and about 26% of patients develop mesangiocapillary or membranoproliferative glomerulonephritis, resulting in renal failure (summary by Reis et al., 2006). (613779)

MalaCards based summary : C3 Deficiency, also known as complement component 3 deficiency, is related to immune system disease and primary immunodeficiency disease, and has symptoms including renal insufficiency, recurrent bacterial infections and nephrotic syndrome. An important gene associated with C3 Deficiency is C3 (Complement C3), and among its related pathways/superpathways are Innate Immune System and Influenza A. The drugs Daratumumab and nivolumab have been mentioned in the context of this disorder. Affiliated tissues include tonsil, bone and testes.

UniProtKB/Swiss-Prot : 71 Complement component 3 deficiency: A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.

Related Diseases for C3 Deficiency

Diseases related to C3 Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 47)
id Related Disease Score Top Affiliating Genes
1 immune system disease 12.0
2 primary immunodeficiency disease 10.6
3 lymphatic system disease 10.6
4 autoimmune disease of exocrine system 10.6
5 hypersensitivity reaction disease 10.6
6 allergic hypersensitivity disease 10.6
7 autoinflammation, panniculitis, and dermatosis syndrome 10.6
8 vasculitis syndromes of the central and peripheral nervous systems 10.6
9 temporal arteritis 10.6
10 hypersensitivity reaction type ii disease 10.6
11 folliculitis 10.1 C3 C3AR1
12 dolk-congenital disorder of glycosylation 10.1 C3 CFP
13 hemolytic uremic syndrome, atypical 3 10.0 C3 CFP
14 granuloma annulare 10.0 C3 CFP
15 sjogren's syndrome 9.9
16 newcastle disease 9.9
17 gastric cardia carcinoma 9.9 C3 CFP
18 meningitis 9.8
19 chronic progressive external ophthalmoplegia 9.7 C3 CD46
20 glomerulonephritis 9.7
21 neonatal meningitis 9.7 C3 CD46 CFP
22 aleutian mink disease 9.7 C3 CD46 CFP
23 skin disease 9.7
24 influenza 9.7
25 lymphoma 9.7
26 bullous pemphigoid 9.7
27 vasculitis 9.7
28 rift valley fever 9.7
29 membranous nephropathy 9.7
30 hiv-1 9.7
31 iga glomerulonephritis 9.7
32 agenesis of the dorsal pancreas 9.6 C3 CD46 CFP
33 spinal cord injury 9.6
34 lipodystrophy 9.6
35 pertussis 9.6
36 systemic lupus erythematosus 9.6
37 lupus erythematosus 9.6
38 obesity 9.6
39 hypoxia 9.6
40 synovitis 9.6
41 mucopolysaccharidosis vii 9.6
42 pneumococcal meningitis 9.6
43 pulmonary hypertension 9.6
44 atherosclerosis 9.6
45 immune-complex glomerulonephritis 9.6
46 pneumonia 9.6
47 hemolytic uremic syndrome, atypical 5 7.3 C3 C3AR1 C5AR2 CD46 CFP HBB

Graphical network of the top 20 diseases related to C3 Deficiency:



Diseases related to C3 Deficiency

Symptoms & Phenotypes for C3 Deficiency

Symptoms via clinical synopsis from OMIM:

54

Laboratory- Abnormalities:
decreased c3 activity
decreased c3 antigen

Genitourinary- Kidneys:
renal failure
nephrotic syndrome
membranoproliferative glomerulonephritis (in about 26%)

Immunology:
autoimmune disease resembling systemic lupus erythematosus (sle, ) (in about 26%)
recurrent bacterial infections


Clinical features from OMIM:

613779

Human phenotypes related to C3 Deficiency:

32
id Description HPO Frequency HPO Source Accession
1 renal insufficiency 32 HP:0000083
2 recurrent bacterial infections 32 HP:0002718
3 nephrotic syndrome 32 HP:0000100
4 membranoproliferative glomerulonephritis 32 very rare (1%) HP:0000793
5 decreased serum complement c3 32 HP:0005421

UMLS symptoms related to C3 Deficiency:


pathological conditions, signs and symptoms

Drugs & Therapeutics for C3 Deficiency

Drugs for C3 Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 35)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Daratumumab Approved Phase 2 945721-28-8
2
nivolumab Approved Phase 2 946414-94-4
3
Dopamine Approved Phase 2 51-61-6, 62-31-7 681
4
Memantine Approved, Investigational Phase 2 19982-08-2 4054
5
Riluzole Approved, Investigational Phase 2 1744-22-5 5070
6
Taurine Approved, Nutraceutical Phase 1, Phase 2 107-35-7 1123
7
Cholecalciferol Approved, Nutraceutical Phase 2 67-97-0 6221 10883523 5280795
8
Ergocalciferol Approved, Nutraceutical Phase 2 50-14-6 5280793
9
Vitamin A Approved, Nutraceutical, Vet_approved Phase 2 11103-57-4, 68-26-8 445354
10
Vitamin D Approved, Nutraceutical, Vet_approved Phase 2 1406-16-2
11 Bone Density Conservation Agents Phase 2
12 Ergocalciferols Phase 2
13 Interferon-alpha Phase 2
14 Micronutrients Phase 2
15 Retinol palmitate Phase 2
16 Trace Elements Phase 2
17 Vitamins Phase 2
18 Antibodies Phase 2
19 Antibodies, Monoclonal Phase 2
20 Immunoglobulins Phase 2
21 Immunoglobulin A Phase 2
22 Antiparkinson Agents Phase 2
23 Dopamine Agents Phase 2
24 Excitatory Amino Acid Antagonists Phase 2
25 Excitatory Amino Acids Phase 2
26 Neurotransmitter Agents Phase 2
27 Calciferol Nutraceutical Phase 2
28 retinol Nutraceutical Phase 2
29 Vitamin D2 Nutraceutical Phase 2
30 Cola Nutraceutical Phase 2
31
Oxaliplatin Approved, Investigational 61825-94-3 5310940 9887054 43805 6857599
32
Iron Approved 7439-89-6 23925
33 Complement C3
34 Complement System Proteins
35
s 1 (combination)

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Effect of Taurine on Glycemic Control in Type I and Type II Diabetic Patients Unknown status NCT01226537 Phase 1, Phase 2 Taurine
2 Vitamin D3 in Systemic Lupus Erythematosus Completed NCT00710021 Phase 2 Vitamin D3;Vitamin D3 placebo
3 An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread Recruiting NCT02060188 Phase 2 Ipilimumab;Nivolumab;Cobimetinib;Daratumumab;anti-LAG-3 antibody
4 Efficacy and Safety of Atacicept in IgA Nephropathy Recruiting NCT02808429 Phase 2 Atacicept 25 mg;Atacicept 75 mg;Placebo;Atacicept 25 mg;Atacicept 75 mg;Atacicept 150 mg;Placebo
5 Therapy in Amyotrophic Lateral Sclerosis With Memantine at 20 mg BID (TAME) Not yet recruiting NCT02118727 Phase 2 Memantine;Placebo (for Memantine)
6 The Predictive Value of Complement C3 in Patients With Advanced Gastric Cancer Completed NCT02425930 S-1+Oxaliplatin
7 A Study to Evaluate the Performance of a Diagnostic Test in ALS Recruiting NCT02759913
8 Prevention of HIV Infection in High-Risk Social Networks of African American Men Who Have Sex With Men (MSM) Active, not recruiting NCT01825252
9 HIV, Computerized Depression Therapy & Cognition Enrolling by invitation NCT03275571

Search NIH Clinical Center for C3 Deficiency

Cochrane evidence based reviews: immune system diseases

Genetic Tests for C3 Deficiency

Genetic tests related to C3 Deficiency:

id Genetic test Affiliating Genes
1 Complement Component 3 Deficiency, Autosomal Recessive 29
2 C3 Deficiency 29
3 C3 Deficiency, Autosomal Recessive 24 C3

Anatomical Context for C3 Deficiency

MalaCards organs/tissues related to C3 Deficiency:

39
Tonsil, Bone, Testes, Colon, T Cells, Brain, B Cells

Publications for C3 Deficiency

Articles related to C3 Deficiency:

(show top 50) (show all 55)
id Title Authors Year
1
Hereditary Homozygous C3 Deficiency. ( 28435995 )
2017
2
Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice. ( 28566429 )
2017
3
C3 deficiency ameliorates the negative effects of irradiation of the young brain on hippocampal development and learning. ( 27029069 )
2016
4
Skipping of exon 27 in C3 gene compromises TED domain and results in complete human C3 deficiency. ( 26847111 )
2016
5
Clinical characteristics and genotype-phenotype correlations in C3 deficiency. ( 26435005 )
2015
6
The effect of Tlr4 and/or C3 deficiency and of neonatal gene therapy on skeletal disease in mucopolysaccharidosis VII mice. ( 25559179 )
2015
7
Human complement C3 deficiency: Th1 induction requires T cell-derived complement C3a and CD46 activation. ( 24321396 )
2014
8
Severe infantile Bordetella pertussis pneumonia in monozygotic twins with a congenital C3 deficiency. ( 23963626 )
2013
9
Rheumatoid factor-positive synovitis in a patient with C3 deficiency. ( 23043374 )
2012
10
Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. ( 23117396 )
2012
11
Novel compound heterozygous mutations in the C3 gene: hereditary C3 deficiency. ( 21501302 )
2011
12
Complement C3 deficiency prevent against the onset of streptozotocin-induced autoimmune diabetes involving expansion of regulatory T cells. ( 21767994 )
2011
13
Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice. ( 22194859 )
2011
14
Effects of C3 deficiency on inflammation and regeneration following spinal cord injury in mice. ( 20800648 )
2010
15
Recurrent meningitis secondary to isolated C3 deficiency. ( 19391010 )
2009
16
[An exceptional component C3 deficiency revealed by serum protein electrophoresis]. ( 19939777 )
2009
17
Screening for C3 deficiency in newborns using microarrays. ( 19390687 )
2009
18
Human C3 deficiency associated with impairments in dendritic cell differentiation, memory B cells, and regulatory T cells. ( 18802120 )
2008
19
The first confirmed case with C3 deficiency caused by compound heterozygous mutations in the C3 gene; a new aspect of pathogenesis for C3 deficiency. ( 18201916 )
2008
20
Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. ( 18562603 )
2008
21
Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice. ( 18836527 )
2008
22
Recurrent meningitis in a family with C3 deficiency. ( 16585828 )
2006
23
A case of C3 deficiency with a novel homozygous two-base deletion in the C3 gene. ( 16158444 )
2005
24
Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus. ( 15781264 )
2005
25
Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice. ( 15734841 )
2005
26
Nonsense-codon-mediated decay in human hereditary complement C3 deficiency. ( 14639503 )
2004
27
Effect of complement component C3 deficiency on experimental Lyme borreliosis in mice. ( 12874322 )
2003
28
Influence of C3 deficiency on atherosclerosis. ( 12081998 )
2002
29
Homozygous hereditary C3 deficiency due to a premature stop codon. ( 12462331 )
2002
30
Recurrent pneumococcal meningitis in homozygous C3 deficiency. ( 12173704 )
2002
31
Identification of a novel mutation (Tyr1081Ter) in sisters with hereditary component C3 deficiency and SLE-like symptoms. ( 11139258 )
2001
32
Hereditary human complement C3 deficiency owing to reduced levels of C3 mRNA. ( 11422912 )
2001
33
Molecular analysis of the third component of canine complement (C3) and identification of the mutation responsible for hereditary canine C3 deficiency. ( 9510185 )
1998
34
Acquired C3 deficiency in patients with alcoholic cirrhosis predisposes to infection and increased mortality. ( 9176087 )
1997
35
Inherited complement C3 deficiency: reduced C3 mRNA and protein levels in a Laotian kindred. ( 8938101 )
1996
36
Compound heterozygous complement C3 deficiency. ( 7890305 )
1995
37
A hereditary C3 deficiency due to aberrant splicing of exon 10. ( 7923934 )
1994
38
Complement C3 deficiency: human, animal, and experimental models. ( 8031472 )
1994
39
Inherited human complement C3 deficiency. An amino acid substitution in the beta-chain (Asp549 to Asn) impairs C3 secretion. ( 7961791 )
1994
40
Inherited complement C3 deficiency: a defect in C3 secretion. ( 8026514 )
1994
41
An association between homozygous C3 deficiency and low levels of anti-pneumococcal capsular polysaccharide antibodies. ( 1544226 )
1992
42
Homozygous hereditary C3 deficiency due to a partial gene deletion. ( 1350678 )
1992
43
Inherited C3 deficiency and meningococcal disease in a teenager. ( 1630861 )
1992
44
Homozygous C3 deficiency associated with IgA nephropathy. ( 1944729 )
1991
45
Molecular basis of hereditary C3 deficiency. ( 2212005 )
1990
46
Molecular basis of complement C3 deficiency in guinea pigs. ( 1973176 )
1990
47
Inherited C3 deficiency of the complement system. ( 3264513 )
1988
48
Inherited C3 deficiency with recurrent infections and glomerulonephritis. ( 2963536 )
1988
49
C3 deficiency presenting as Raynaud's phenomenon in a 6-year-old girl with a persistent erythematous rash. ( 3742869 )
1986
50
Selective C3 deficiency due to C3 nephritic factor in an apparently healthy girl. ( 3834579 )
1985

Variations for C3 Deficiency

UniProtKB/Swiss-Prot genetic disease variations for C3 Deficiency:

71
id Symbol AA change Variation ID SNP ID
1 C3 p.Asp549Asn VAR_001985

ClinVar genetic disease variations for C3 Deficiency:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 C3 C3, 61-BP DEL, EX18 deletion Pathogenic
2 C3 NG_009557.1: g.(28821_28842)_(29653_29671)del deletion Pathogenic GRCh38 Chromosome 19, 6695981: 6696831
3 C3 C3, IVS38AS, A-G single nucleotide variant Pathogenic

Expression for C3 Deficiency

Search GEO for disease gene expression data for C3 Deficiency.

Pathways for C3 Deficiency

GO Terms for C3 Deficiency

Cellular components related to C3 Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 tertiary granule lumen GO:1904724 8.62 CFP HBB

Biological processes related to C3 Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 innate immune response GO:0045087 9.61 C3 CD46 CFP
2 inflammatory response GO:0006954 9.5 C3 C3AR1 C5AR2
3 positive regulation of angiogenesis GO:0045766 9.46 C3 C3AR1
4 complement activation GO:0006956 9.4 C3 CFP
5 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007200 9.37 C3AR1 C5AR2
6 positive regulation of vascular endothelial growth factor production GO:0010575 9.26 C3 C3AR1
7 neutrophil degranulation GO:0043312 9.26 C3 C3AR1 CFP HBB
8 complement activation, alternative pathway GO:0006957 9.16 C3 CFP
9 regulation of complement activation GO:0030449 9.02 C3 C3AR1 C5AR2 CD46 CFP

Sources for C3 Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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