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GeneBe

CFB

complement factor B, the group of Sushi domain containing|Complement system activation components

Basic information

Region (hg38): 6:31945649-31952086

Previous symbols: [ "BFD", "BF" ]

Links

ENSG00000243649NCBI:629OMIM:138470HGNC:1037Uniprot:P00751AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • complement factor b deficiency (Moderate), mode of inheritance: AR
  • atypical hemolytic-uremic syndrome with B factor anomaly (Strong), mode of inheritance: AD
  • atypical hemolytic-uremic syndrome with B factor anomaly (Moderate), mode of inheritance: AD
  • atypical hemolytic-uremic syndrome with B factor anomaly (Limited), mode of inheritance: Unknown
  • atypical hemolytic-uremic syndrome with B factor anomaly (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hemolytic uremic syndrome, atypical, susceptibility to, 4; Complement factor B deficiencyAD/ARAllergy/Immunology/Infectious; Hematologic; Pharmacogenomic; RenalIn hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications); In Complement factor B deficiency, individuals may manifest with severe and recurrent infections due to encapsulated bacteria, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficialAllergy/Immunology/Infectious; Hematologic; Renal6903190; 6898304; 7452889; 16518403; 16936732; 17182750; 20301541; 24152280

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CFB gene.

  • not provided (317 variants)
  • Atypical hemolytic-uremic syndrome with B factor anomaly (55 variants)
  • Macular degeneration (48 variants)
  • Atypical hemolytic-uremic syndrome (18 variants)
  • Complement component 2 deficiency (16 variants)
  • Inborn genetic diseases (15 variants)
  • not specified (14 variants)
  • Complement factor b deficiency (6 variants)
  • Atypical hemolytic-uremic syndrome with B factor anomaly;Complement factor b deficiency;Age related macular degeneration 14 (4 variants)
  • Kidney disorder (4 variants)
  • Focal segmental glomerulosclerosis (3 variants)
  • CFB-related condition (2 variants)
  • Factor B fast/slow polymorphism (2 variants)
  • Atypical hemolytic-uremic syndrome with B factor anomaly;Age related macular degeneration 14;Complement factor b deficiency (2 variants)
  • Age related macular degeneration 14 (2 variants)
  • Age related macular degeneration 14;Complement factor b deficiency;Atypical hemolytic-uremic syndrome with B factor anomaly (2 variants)
  • CFB-related disorders (1 variants)
  • Age related macular degeneration 14;Atypical hemolytic-uremic syndrome with B factor anomaly;Complement factor b deficiency (1 variants)
  • BF*FA/S (1 variants)
  • Complement component 2 deficiency;Age related macular degeneration 14 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CFB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
9
clinvar
68
clinvar
2
clinvar
79
missense
1
clinvar
146
clinvar
9
clinvar
2
clinvar
158
nonsense
3
clinvar
3
start loss
0
frameshift
6
clinvar
6
inframe indel
2
clinvar
2
splice donor/acceptor (+/-2bp)
3
clinvar
3
splice region
6
9
1
16
non coding
4
clinvar
45
clinvar
13
clinvar
62
Total 1 0 173 122 17

Variants in CFB

This is a list of pathogenic ClinVar variants found in the CFB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
6-31945661-A-G Atypical hemolytic-uremic syndrome • Macular degeneration • Complement component 2 deficiency • Age related macular degeneration 14 Conflicting classifications of pathogenicity (Jan 13, 2018)356265
6-31946023-T-C Atypical hemolytic-uremic syndrome with B factor anomaly • Macular degeneration Uncertain significance (Jan 12, 2018)904798
6-31946032-CG-C Atypical hemolytic-uremic syndrome • Macular degeneration Likely benign (Jun 14, 2016)356266
6-31946219-G-A Macular degeneration • Atypical hemolytic-uremic syndrome with B factor anomaly • Atypical hemolytic-uremic syndrome with B factor anomaly;Complement factor b deficiency;Age related macular degeneration 14 Uncertain significance (Jan 03, 2022)356267
6-31946236-C-A Likely benign (May 12, 2022)1993265
6-31946239-C-A Uncertain significance (Jun 16, 2023)1972195
6-31946245-A-G Likely benign (Jan 03, 2024)2993673
6-31946247-T-A Age related macular degeneration 14 • Atypical hemolytic-uremic syndrome • Macular degeneration • Complement component 2 deficiency • not specified • Atypical hemolytic-uremic syndrome with B factor anomaly • CFB-related condition • Complement factor b deficiency;Age related macular degeneration 14;Atypical hemolytic-uremic syndrome with B factor anomaly Benign/Likely benign (Jan 29, 2024)16077
6-31946260-C-T Likely benign (Feb 05, 2022)1667892
6-31946269-G-A Likely benign (Aug 01, 2023)2722524
6-31946273-C-A Uncertain significance (Oct 28, 2021)1464683
6-31946283-G-A Inborn genetic diseases Uncertain significance (May 25, 2022)2397647
6-31946285-G-A Uncertain significance (Feb 26, 2021)1375925
6-31946291-C-T CFB-related condition Conflicting classifications of pathogenicity (Jan 04, 2024)2989031
6-31946296-G-C Likely benign (Aug 23, 2023)2754714
6-31946304-C-G Likely benign (Dec 11, 2023)2133063
6-31946363-T-C Likely benign (Oct 22, 2023)2991268
6-31946365-C-G Uncertain significance (Aug 30, 2022)1961635
6-31946365-C-T Likely benign (Sep 25, 2022)1921287
6-31946402-C-T Factor B fast/slow polymorphism • Macular degeneration • Atypical hemolytic-uremic syndrome • Complement component 2 deficiency • Atypical hemolytic-uremic syndrome with B factor anomaly • Complement factor b deficiency;Age related macular degeneration 14;Atypical hemolytic-uremic syndrome with B factor anomaly • Focal segmental glomerulosclerosis • CFB-related condition Benign/Likely benign (Jan 31, 2024)16076
6-31946403-G-A Factor B fast/slow polymorphism • BF*FA/S • Age related macular degeneration 14 • Atypical hemolytic-uremic syndrome • Macular degeneration • Complement component 2 deficiency • not specified • Atypical hemolytic-uremic syndrome with B factor anomaly • Age related macular degeneration 14;Complement component 2 deficiency • Focal segmental glomerulosclerosis Benign/Likely benign (Feb 01, 2024)16075
6-31946405-C-G Uncertain significance (Jul 12, 2023)1940636
6-31946418-G-A Uncertain significance (Nov 23, 2022)2812266
6-31946426-G-A Atypical hemolytic-uremic syndrome with B factor anomaly Uncertain significance (Oct 04, 2019)830012
6-31946426-G-C Uncertain significance (Jun 06, 2021)1376133

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CFBprotein_codingprotein_codingENST00000425368 1824387
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0003351.001257220261257480.000103
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.483264100.7940.00002535006
Missense in Polyphen92143.830.639661707
Synonymous0.7341451570.9250.000009821447
Loss of Function3.991441.90.3340.00000231501

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001810.000177
Ashkenazi Jewish0.000.00
East Asian0.0001630.000163
Finnish0.00009240.0000924
European (Non-Finnish)0.0001160.000114
Middle Eastern0.0001630.000163
South Asian0.00009870.0000980
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. It has also been implicated in proliferation and differentiation of preactivated B- lymphocytes, rapid spreading of peripheral blood monocytes, stimulation of lymphocyte blastogenesis and lysis of erythrocytes. Ba inhibits the proliferation of preactivated B-lymphocytes.;
Disease
DISEASE: Hemolytic uremic syndrome atypical 4 (AHUS4) [MIM:612924]: An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. {ECO:0000269|PubMed:17182750, ECO:0000269|PubMed:20513133}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.; DISEASE: Complement factor B deficiency (CFBD) [MIM:615561]: An immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. {ECO:0000269|PubMed:24152280}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Complement and coagulation cascades - Homo sapiens (human);Staphylococcus aureus infection - Homo sapiens (human);Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement Activation;Complement and Coagulation Cascades;Innate Immune System;Immune System;Activation of C3 and C5;Initial triggering of complement;Regulation of Complement cascade;Complement cascade;Alternative complement activation (Consensus)

Intolerance Scores

loftool
0.370
rvis_EVS
1.64
rvis_percentile_EVS
96.15

Haploinsufficiency Scores

pHI
0.429
hipred
N
hipred_score
0.332
ghis
0.434

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.928

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Cfb
Phenotype
homeostasis/metabolism phenotype; normal phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; hematopoietic system phenotype; reproductive system phenotype;

Gene ontology

Biological process
proteolysis;complement activation;complement activation, alternative pathway;regulation of complement activation
Cellular component
extracellular region;extracellular space;plasma membrane;extracellular exosome;blood microparticle
Molecular function
complement binding;serine-type endopeptidase activity;protein binding