CFB

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

Basic information

Region (hg38): 6:31945650-31952086

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

Links

ENSG00000243649

∙ NCBI:629 ∙ OMIM:138470 ∙ HGNC:1037 ∙ Uniprot:P00751 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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: CGD

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 ClinVar and linked to the CFB gene.

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 clinvar	107 clinvar	1 clinvar	118
missense	1 clinvar		235 clinvar	16 clinvar	3 clinvar	255
nonsense			7 clinvar	1 clinvar		8
start loss						0
frameshift	1 clinvar	1 clinvar	8 clinvar			10
splice donor/acceptor (+/-2bp)		1 clinvar	5 clinvar			6
Total	2	2	265	124	4

Highest pathogenic variant AF is 0.00000752452

Loading clinvar variants...

GnomAD

Source: gnomAD

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: 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

	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