CFB
Basic information
Region (hg38): 6:31945650-31952086
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 (Limited), mode of inheritance: Unknown
- atypical hemolytic-uremic syndrome with B factor anomaly (Limited), 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 (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 (457 variants)
- Inborn_genetic_diseases (57 variants)
- Atypical_hemolytic-uremic_syndrome_with_B_factor_anomaly (50 variants)
- Macular_degeneration (36 variants)
- CFB-related_disorder (19 variants)
- not_specified (15 variants)
- Atypical_hemolytic-uremic_syndrome (13 variants)
- Complement_factor_b_deficiency (12 variants)
- Complement_component_2_deficiency (8 variants)
- Age_related_macular_degeneration_14 (6 variants)
- Kidney_disorder (3 variants)
- Decreased_total_neutrophil_count (1 variants)
- Decreased_total_lymphocyte_count (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. These statistics are base on transcript: NM_000001710.6. Only rare variants are included in the table.
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.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 10 | 107 | 118 | |||
missense | 235 | 16 | 255 | |||
nonsense | 8 | |||||
start loss | 0 | |||||
frameshift | 10 | |||||
splice donor/acceptor (+/-2bp) | 6 | |||||
Total | 2 | 2 | 265 | 124 | 4 |
Highest pathogenic variant AF is 0.00000752452
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