CFHD
MCID: CMP042
MIFTS: 44

Complement Factor H Deficiency (CFHD)

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

Aliases & Classifications for Complement Factor H Deficiency

MalaCards integrated aliases for Complement Factor H Deficiency:

Name: Complement Factor H Deficiency 57 72 13 70
Factor H Deficiency 57 72 29 6
Cfh Deficiency 57 72
Cfhd 57 72
Membranoproliferative Glomerulonephritis, Type Ii 70
Membranoproliferative Glomerulonephritis Type 2 58
Immunodeficiency with Factor H Anomaly 58
Deficiency, Complement Factor H 39
C3 Glomerulopathy 1; C3g1 57
Dense Deposit Disease 58
C3 Glomerulopathy 1 57
C3g1 57

Characteristics:

Orphanet epidemiological data:

58
dense deposit disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

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

Miscellaneous:
variable phenotype
onset in infancy or childhood
some patients may be asymptomatic


HPO:

31
complement factor h deficiency:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:

Orphanet: 58  
Rare renal diseases
Rare immunological diseases


External Ids:

OMIM® 57 609814
MeSH 44 D007154
MESH via Orphanet 45 D015432
ICD10 via Orphanet 33 D84.1 N03.6
UMLS via Orphanet 71 C0268743 C0398777
UMLS 70 C0268743 C0398777

Summaries for Complement Factor H Deficiency

OMIM® : 57 Complement factor H deficiency (CFHD) has a variable phenotype. Some patients present with recurrent infections, including increased susceptibility to meningococcal infections, whereas others develop renal disease manifest primarily as C3 glomerulopathy. Affected individuals usually present in the first decades of life with nonspecific findings such as hematuria and may progress to chronic renal failure. As complement factor H is the key regulator of the alternative pathway of the complement system, CFH deficiency results in inappropriate activation of the alternative complement pathway. Laboratory features usually include decreased serum levels of factor H, due to the genetic defect, as well as secondarily decreased levels of complement component C3 (120700) and other alternative pathway components, consistent with consumption of these factors. The renal phenotype is now considered to be a form of C3 glomerulopathy (C3G), which is a pathologic entity in which C3 is deposited within the kidney glomerulus in the mesangial or intramembranous space; this occurs in the absence of immune complexes or immunoglobulins. Terms used to describe this disease include membranoproliferative glomerulonephritis type II (MPGN II), mesangial glomerulonephritis, dense deposit disease (DDD), and C3 glomerulonephritis (summary by Ault, 2000, reviews by Riedl et al., 2017 and Wong and Kavanagh, 2018). (609814) (Updated 05-Apr-2021)

MalaCards based summary : Complement Factor H Deficiency, also known as factor h deficiency, is related to enterocolitis and complement component 3 deficiency. An important gene associated with Complement Factor H Deficiency is CFH (Complement Factor H), and among its related pathways/superpathways are Immune response Lectin induced complement pathway and Creation of C4 and C2 activators. The drugs Immunoglobulin A and Aspirin have been mentioned in the context of this disorder. Affiliated tissues include kidney and endothelial, and related phenotypes are hematuria and chronic kidney disease

UniProtKB/Swiss-Prot : 72 Complement factor H deficiency: A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.

Wikipedia : 73 Factor H is a member of the regulators of complement activation family and is a complement control... more...

Related Diseases for Complement Factor H Deficiency

Diseases related to Complement Factor H Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 77)
# Related Disease Score Top Affiliating Genes
1 enterocolitis 29.8 CFH CD46
2 complement component 3 deficiency 29.8 CFH CD46
3 membranoproliferative glomerulonephritis 29.7 CFH CD46
4 glomerulonephritis 29.7 CFI CFH CD46
5 end stage renal disease 29.6 CFHR1 CFH CD46
6 hemolytic-uremic syndrome 29.6 CFI CFHR1 CFH CD46
7 hemolytic uremic syndrome, atypical 1 29.5 CFI CFHR1 CFH CD46
8 retinal drusen 29.3 CFI CFHR1 CFH
9 genetic atypical hemolytic-uremic syndrome 29.1 CFI CFHR1 CFH CD46
10 c3 glomerulopathy 29.1 CFI CFHR1 CFH CD46
11 thrombotic thrombocytopenic purpura 29.0 CFI CFH CD46
12 chronic kidney disease 28.9 CFI CFHR1 CFH
13 complement deficiency 28.8 CFI CFHR1 CFH CD46
14 hemolytic anemia 28.8 CFI CFHR1 CFH CD46
15 macular degeneration, age-related, 1 28.8 CFI CFHR1 CFH CD46
16 thrombocytopenia 28.5 CFI CFHR1 CFH CD46
17 complement factor i deficiency 11.3
18 c3 glomerulopathy 3 10.9
19 nephrotic syndrome 10.6
20 mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 10.4
21 glomerulopathy with fibronectin deposits 2 10.3
22 fibrillary glomerulonephritis 10.3
23 immunotactoid glomerulopathy 10.3
24 immunotactoid or fibrillary glomerulopathy 10.3
25 crescentic glomerulonephritis 10.2
26 thrombotic microangiopathy 10.2
27 myeloma, multiple 10.2
28 membranous nephropathy 10.2
29 acute poststreptococcal glomerulonephritis 10.2
30 monoclonal gammopathy of uncertain significance 10.2
31 glomerular disease 10.2
32 atherosclerosis susceptibility 10.0
33 diabetes and deafness, maternally inherited 10.0
34 complement component 3 deficiency, autosomal recessive 10.0
35 acute kidney tubular necrosis 10.0
36 focal segmental glomerulosclerosis 10.0
37 acute proliferative glomerulonephritis 10.0
38 mycoplasma pneumoniae pneumonia 10.0
39 pyuria 10.0
40 diffuse glomerulonephritis 10.0
41 vasculitis 10.0
42 amyloidosis 10.0
43 yemenite deaf-blind hypopigmentation syndrome 10.0
44 proteinuria, chronic benign 10.0
45 proliferative glomerulonephritis 10.0
46 mesangial proliferative glomerulonephritis 10.0
47 kidney disease 10.0
48 retinal disease 10.0
49 lupus erythematosus 10.0
50 dense deposit disease 10.0

Graphical network of the top 20 diseases related to Complement Factor H Deficiency:



Diseases related to Complement Factor H Deficiency

Symptoms & Phenotypes for Complement Factor H Deficiency

Human phenotypes related to Complement Factor H Deficiency:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 hematuria 31 HP:0000790
2 chronic kidney disease 31 HP:0012622
3 recurrent bacterial infections 31 HP:0002718
4 glomerular subendothelial electron-dense deposits 31 HP:0004746
5 thickened glomerular basement membrane 31 HP:0004722
6 decreased serum complement factor h 31 HP:0005369
7 depletion of components of the alternative complement pathway 31 HP:0005389

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Genitourinary Kidneys:
hematuria
progressive renal failure
membranoproliferative glomerulonephritis type ii
thickening of the glomerular basement membrane on renal biopsy
deposition of complement component c3 in glomerular basement membrane

Immunology:
depletion of components of the alternative complement pathway
continuous activation of the alternative complement pathway
hypocomplementemia
increased susceptibility to certain bacterial infections, especially neisseria meningitidis

Laboratory Abnormalities:
decreased serum complement factor h
hypocomplementemia
normal levels of complement factor h, but impaired function

Clinical features from OMIM®:

609814 (Updated 05-Apr-2021)

Drugs & Therapeutics for Complement Factor H Deficiency

Drugs for Complement Factor H Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Immunoglobulin A Phase 2
2
Aspirin Approved, Vet_approved Phase 1 50-78-2 2244
3 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 1
4 Angiotensin-Converting Enzyme Inhibitors Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomized, Double Blind, Placebo Controlled Phase 2 Study to Evaluate the Safety and Efficacy of Avacopan (CCX168) in Patients With C3 Glomerulopathy Recruiting NCT03301467 Phase 2 Avacopan;Avacopan Matching Placebo
2 A Phase 2 Study to Evaluate the Safety and Effect on Proteinuria of OMS721 in Subjects With IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy, or C3 Glomerulopathy Including Dense Deposit Disease Recruiting NCT02682407 Phase 2
3 A Phase 2 Study to Evaluate the Safety and Biologic Activity of APL- 2 in Patients With IgA Nephropathy, Lupus Nephritis, Primary Membranous Nephropathy, or C3 Glomerulopathy (C3 Glomerulonephritis and Dense Deposit Disease) Active, not recruiting NCT03453619 Phase 2 APL-2
4 Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy Completed NCT01221181 Phase 1 Eculizumab
5 A Pilot, Open-label, Multicenter Clinical Trial of CDX-1135 in Pediatric and Adult Patients With Dense Deposit Disease Terminated NCT01791686 Phase 1 CDX-1135
6 A Pilot, Open-Label Single Center Trial of TP10 in Pediatric and Adult Patients With C3 Glomerulopathy (C3G) Withdrawn NCT02302755 Phase 1 TP10
7 Sulodexide Treatment in Patients With Dense Deposit Disease Withdrawn NCT00583427 Phase 1 Sulodexide

Search NIH Clinical Center for Complement Factor H Deficiency

Genetic Tests for Complement Factor H Deficiency

Genetic tests related to Complement Factor H Deficiency:

# Genetic test Affiliating Genes
1 Factor H Deficiency 29 CFH

Anatomical Context for Complement Factor H Deficiency

MalaCards organs/tissues related to Complement Factor H Deficiency:

40
Kidney, Endothelial

Publications for Complement Factor H Deficiency

Articles related to Complement Factor H Deficiency:

(show top 50) (show all 102)
# Title Authors PMID Year
1
Factor H and the pathogenesis of renal diseases. 57 61 6
10975323 2000
2
Inherited factor H deficiency and collagen type III glomerulopathy. 61 6 57
7742208 1995
3
Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. 57 6
17018561 2007
4
Deletion of Lys224 in regulatory domain 4 of Factor H reveals a novel pathomechanism for dense deposit disease (MPGN II). 57 6
16612335 2006
5
Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases. 57 6
14978182 2004
6
Molecular basis for factor H and FHL-1 deficiency in an Italian family. 6 57
10803850 2000
7
Combined homozygous factor H and heterozygous C2 deficiency in an Italian family. 57 6
2966809 1988
8
H deficiency in two brothers with atypical dense intramembranous deposit disease. 57 6
2950269 1986
9
Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. 61 57
12091909 2002
10
Disruption of disulfide bonds is responsible for impaired secretion in human complement factor H deficiency. 6 61
10206995 1999
11
Human factor H deficiency. Mutations in framework cysteine residues and block in H protein secretion and intracellular catabolism. 57 61
9312129 1997
12
Heterozygous and homozygous factor H deficiency states in a Dutch family. 61 57
8809142 1996
13
Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency. 61 57
7883953 1995
14
Hereditary, complete deficiency of complement factor H associated with recurrent meningococcal disease. 61 57
2532396 1989
15
Diseases of complement dysregulation-an overview. 57
29327071 2018
16
C3 Glomerulopathy. 57
27056062 2017
17
Phenotypic Characterization of Complement Factor H R1210C Rare Genetic Variant in Age-Related Macular Degeneration. 6
25880396 2015
18
Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. 6
24036949 2013
19
A rare penetrant mutation in CFH confers high risk of age-related macular degeneration. 6
22019782 2011
20
Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). 57
16299065 2006
21
Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. 57
15800116 2005
22
Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome. 6
12697737 2003
23
The molecular basis for hereditary porcine membranoproliferative glomerulonephritis type II: point mutations in the factor H coding sequence block protein secretion. 57
12466119 2002
24
Complement in glomerulonephritis. 57
12091912 2002
25
Partial H (beta 1H) deficiency and glomerulonephritis in two families. 57
6461667 1982
26
Complement activity is regulated in C3 glomerulopathy by IgG-factor H fusion proteins with and without properdin targeting domains. 61
33129896 2021
27
Atypical hemolytic uremic syndrome: An unusual postoperative complication. 61
29426622 2018
28
Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM. 61
29389016 2018
29
Kidney Transplantation in Patients with Atypical Hemolytic Uremic Syndrome due to Complement Factor H Deficiency: Impact of Liver Transplantation. 61
29215813 2018
30
Long-term successful liver-kidney transplantation in a child with atypical hemolytic uremic syndrome caused by homozygous factor H deficiency. 61
27744619 2016
31
Distinct roles for the complement regulators factor H and Crry in protection of the kidney from injury. 61
27165610 2016
32
Partial Complement Factor H Deficiency Associates with C3 Glomerulopathy and Thrombotic Microangiopathy. 61
26374608 2016
33
Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy. 61
26924054 2016
34
Novel factor H mutation associated with familial membranoproliferative glomerulonephritis type I. 61
26289290 2015
35
Eculizumab in neonatal hemolytic uremic syndrome with homozygous factor H deficiency. 61
25149852 2014
36
ADAMTS-13 in the Diagnosis and Management of Thrombotic Microangiopathies. 61
25386342 2014
37
A novel use of intravenous immunoglobulin is not restricted to complement hypercatabolism because of factor H deficiency. 61
24919726 2014
38
Anesthetic management of living donor liver transplantation for complement factor H deficiency hemolytic uremic syndrome: a case report. 61
25006375 2014
39
C3 dysregulation due to factor H deficiency is mannan-binding lectin-associated serine proteases (MASP)-1 and MASP-3 independent in vivo. 61
24279761 2014
40
A rare case: childhood-onset C3 glomerulonephritis due to homozygous factor H deficiency. 61
28509298 2013
41
Genotype/phenotype correlations in complement factor H deficiency arising from uniparental isodisomy. 61
23870792 2013
42
Combined paediatric liver-kidney transplantation: analysis of our experience and literature review. 61
24300631 2013
43
Loss of properdin exacerbates C3 glomerulopathy resulting from factor H deficiency. 61
23184055 2013
44
Complement factor H functional assay may help to monitor atypical haemolytic uraemic syndrome: a pilot study. 61
23627188 2013
45
Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice. 61
22918646 2012
46
Postpartum aHUS secondary to a genetic abnormality in factor H acquired through liver transplantation. 61
22420623 2012
47
Rescue therapy with eculizumab in a transplant recipient with atypical haemolytic-uraemic syndrome. 61
26069742 2012
48
Eculizumab in atypical haemolytic-uraemic syndrome allows cessation of plasma exchange and dialysis. 61
26069744 2012
49
Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report. 61
22206706 2011
50
Heterogeneous pattern of renal disease associated with homozygous factor H deficiency. 61
21396679 2011

Variations for Complement Factor H Deficiency

ClinVar genetic disease variations for Complement Factor H Deficiency:

6 (show all 12)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CFH NM_000186.3(CFH):c.1606T>C (p.Cys536Arg) SNV Pathogenic 16543 rs121913052 GRCh37: 1:196684809-196684809
GRCh38: 1:196715679-196715679
2 CFH NM_000186.3(CFH):c.2876G>A (p.Cys959Tyr) SNV Pathogenic 16544 rs121913053 GRCh37: 1:196709842-196709842
GRCh38: 1:196740712-196740712
3 CFH NM_000186.3(CFH):c.565G>T (p.Glu189Ter) SNV Pathogenic 16547 rs121913054 GRCh37: 1:196646743-196646743
GRCh38: 1:196677613-196677613
4 CFH NM_000186.3(CFH):c.1291T>A (p.Cys431Ser) SNV Pathogenic 16551 rs121913056 GRCh37: 1:196659324-196659324
GRCh38: 1:196690194-196690194
5 CFH NM_000186.3(CFH):c.380G>T (p.Arg127Leu) SNV Pathogenic 16554 rs121913058 GRCh37: 1:196645148-196645148
GRCh38: 1:196676018-196676018
6 CFH NM_001014975.2(CFH):c.668_670AGA[1] (p.Lys224del) Microsatellite Pathogenic 16555 rs796052138 GRCh37: 1:196648801-196648803
GRCh38: 1:196679671-196679673
7 CFH NM_000186.4(CFH):c.2517C>A SNV Pathogenic 591005 rs1362306576 GRCh37: 1:196706057-196706057
GRCh38: 1:196736927-196736927
8 CFH NM_000186.3(CFH):c.3628C>T (p.Arg1210Cys) SNV Pathogenic 16558 rs121913059 GRCh37: 1:196716375-196716375
GRCh38: 1:196747245-196747245
9 CFH NM_000186.4(CFH):c.1198C>A (p.Gln400Lys) SNV Uncertain significance 1006921 GRCh37: 1:196659231-196659231
GRCh38: 1:196690101-196690101
10 CFH NM_000186.4(CFH):c.3169G>A (p.Ala1057Thr) SNV Uncertain significance 1030653 GRCh37: 1:196712617-196712617
GRCh38: 1:196743487-196743487
11 CFH NM_000186.3(CFH):c.481G>T (p.Ala161Ser) SNV Uncertain significance 625915 rs777300338 GRCh37: 1:196646659-196646659
GRCh38: 1:196677529-196677529
12 CFH NM_000186.3(CFH):c.2461C>T (p.His821Tyr) SNV Uncertain significance 625916 rs367687415 GRCh37: 1:196706001-196706001
GRCh38: 1:196736871-196736871

UniProtKB/Swiss-Prot genetic disease variations for Complement Factor H Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 CFH p.Cys536Arg VAR_019405 rs121913052
2 CFH p.Cys959Tyr VAR_019406 rs121913053
3 CFH p.Gln1076Glu VAR_025873 rs62625015
4 CFH p.Asp1119Gly VAR_025874 rs575109631
5 CFH p.Thr1184Arg VAR_025881
6 CFH p.Arg1210Cys VAR_025885 rs121913059
7 CFH p.Arg1215Gln VAR_025887
8 CFH p.Arg127Leu VAR_031978 rs121913058
9 CFH p.Cys431Ser VAR_031981 rs121913056
10 CFH p.Cys673Ser VAR_031982

Expression for Complement Factor H Deficiency

Search GEO for disease gene expression data for Complement Factor H Deficiency.

Pathways for Complement Factor H Deficiency

Pathways related to Complement Factor H Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.53 CFI CFH CD46
2
Show member pathways
11.29 CFI CFH CD46
3 11.24 CFI CFH
4 11.09 CFI CFHR1 CFH CD46

GO Terms for Complement Factor H Deficiency

Cellular components related to Complement Factor H Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 blood microparticle GO:0072562 8.62 CFHR1 CFH

Biological processes related to Complement Factor H Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 9.5 CFI CFH CD46
2 complement activation, classical pathway GO:0006958 9.37 CFI CD46
3 innate immune response GO:0045087 9.33 CFI CFH CD46
4 complement activation GO:0006956 9.26 CFHR1 CFH
5 viral process GO:0016032 9.13 CFI CFH CD46
6 regulation of complement activation GO:0030449 8.92 CFI CFHR1 CFH CD46

Sources for Complement Factor H Deficiency

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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