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
Phenotypes
GenCC
Source:
- complement factor b deficiency (Moderate), mode of inheritance: AR
- atypical hemolytic-uremic syndrome with B factor anomaly (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hemolytic uremic syndrome, atypical, susceptibility to, 4; Complement factor B deficiency | AD/AR | Allergy/Immunology/Infectious; Hematologic; Pharmacogenomic; Renal | In 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 beneficial | Allergy/Immunology/Infectious; Hematologic; Renal | 6903190; 6898304; 7452889; 16518403; 16936732; 17182750; 20301541; 24152280 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (293 variants)
- Atypical hemolytic-uremic syndrome with B factor anomaly (59 variants)
- Macular degeneration (52 variants)
- Atypical hemolytic-uremic syndrome (20 variants)
- Complement component 2 deficiency (18 variants)
- not specified (12 variants)
- Inborn genetic diseases (10 variants)
- Complement factor b deficiency (8 variants)
- Kidney disorder (4 variants)
- Focal segmental glomerulosclerosis (3 variants)
- Atypical hemolytic-uremic syndrome with B factor anomaly;Complement factor b deficiency;Age related macular degeneration 14 (3 variants)
- Atypical hemolytic-uremic syndrome with B factor anomaly;Age related macular degeneration 14;Complement factor b deficiency (3 variants)
- Age related macular degeneration 14 (3 variants)
- Factor B fast/slow polymorphism (2 variants)
- Complement factor b deficiency;Age related macular degeneration 14;Atypical hemolytic-uremic syndrome with B factor anomaly (1 variants)
- Complement factor b deficiency;Atypical hemolytic-uremic syndrome with B factor anomaly;Age related macular degeneration 14 (1 variants)
- Lymphopenia;Neutropenia (1 variants)
- BF*FA/S (1 variants)
- Age related macular degeneration 14;Complement factor b deficiency;Atypical hemolytic-uremic syndrome with B factor anomaly (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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | 66 | 3 | 76 | ||
| missense | 133 | 17 | 3 | 153 | ||
| nonsense | 1 | 2 | 1 | 4 | ||
| start loss | 0 | |||||
| frameshift | 1 | 5 | 6 | |||
| inframe indel | 3 | 3 | ||||
| splice variant | 9 | 9 | 2 | 20 | ||
| non coding | 4 | 43 | 13 | 60 | ||
| Total | 2 | 0 | 163 | 136 | 21 |
Highest pathogenic variant AF is 0.0000263
Variants in CFB
This is a list of pathogenic ClinVar variants found in the CFB region.
| 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 interpretations of pathogenicity (Jan 13, 2018) | ||
| 6-31946023-T-C | Atypical hemolytic-uremic syndrome with B factor anomaly • Macular degeneration | Uncertain significance (Jan 12, 2018) | ||
| 6-31946032-CG-C | Atypical hemolytic-uremic syndrome • Macular degeneration | Likely benign (Jun 14, 2016) | ||
| 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) | ||
| 6-31946236-C-A | Likely benign (May 12, 2022) | |||
| 6-31946239-C-A | Uncertain significance (May 07, 2022) | |||
| 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 • Complement factor b deficiency;Age related macular degeneration 14;Atypical hemolytic-uremic syndrome with B factor anomaly | Benign/Likely benign (Nov 01, 2022) | ||
| 6-31946260-C-T | Likely benign (Feb 05, 2022) | |||
| 6-31946273-C-A | Uncertain significance (Oct 28, 2021) | |||
| 6-31946283-G-A | Inborn genetic diseases | Uncertain significance (May 25, 2022) | ||
| 6-31946285-G-A | Uncertain significance (Sep 01, 2021) | |||
| 6-31946304-C-G | Likely benign (May 03, 2022) | |||
| 6-31946365-C-G | Uncertain significance (Aug 30, 2022) | |||
| 6-31946365-C-T | Likely benign (Sep 25, 2022) | |||
| 6-31946402-C-T | Factor B fast/slow polymorphism • Atypical hemolytic-uremic syndrome • Complement component 2 deficiency • Macular degeneration • Atypical hemolytic-uremic syndrome with B factor anomaly • Focal segmental glomerulosclerosis • Complement factor b deficiency;Age related macular degeneration 14;Atypical hemolytic-uremic syndrome with B factor anomaly | Benign/Likely benign (Nov 01, 2022) | ||
| 6-31946403-G-A | Factor B fast/slow polymorphism • BF*FA/S • Age related macular degeneration 14 • Complement component 2 deficiency • Atypical hemolytic-uremic syndrome • Macular degeneration • not specified • Atypical hemolytic-uremic syndrome with B factor anomaly • Focal segmental glomerulosclerosis • Complement component 2 deficiency;Age related macular degeneration 14 | Benign/Likely benign (Oct 22, 2022) | ||
| 6-31946405-C-G | Uncertain significance (Mar 18, 2022) | |||
| 6-31946426-G-A | Atypical hemolytic-uremic syndrome with B factor anomaly | Uncertain significance (Oct 04, 2019) | ||
| 6-31946426-G-C | Uncertain significance (Sep 24, 2021) | |||
| 6-31946427-AG-A | Complement factor b deficiency | Uncertain significance (Mar 08, 2021) | ||
| 6-31946429-G-C | Uncertain significance (Sep 01, 2021) | |||
| 6-31946447-G-A | Uncertain significance (Sep 16, 2022) | |||
| 6-31946456-C-T | Uncertain significance (Feb 20, 2021) | |||
| 6-31946457-G-A | Uncertain significance (Feb 28, 2022) | |||
| 6-31946488-C-T | Uncertain significance (May 09, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CFB | protein_coding | protein_coding | ENST00000425368 | 18 | 24387 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000335 | 1.00 | 125722 | 0 | 26 | 125748 | 0.000103 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.48 | 326 | 410 | 0.794 | 0.0000253 | 5006 |
| Missense in Polyphen | 92 | 143.83 | 0.63966 | 1707 | ||
| Synonymous | 0.734 | 145 | 157 | 0.925 | 0.00000982 | 1447 |
| Loss of Function | 3.99 | 14 | 41.9 | 0.334 | 0.00000231 | 501 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000181 | 0.000177 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000116 | 0.000114 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.0000987 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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