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 (Strong), 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
• atypical hemolytic-uremic syndrome with B factor anomaly (Moderate), 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.

• CFB-related disorder (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			10	89	2	101
missense	1		183	9	2	195
nonsense			7			7
start loss						0
frameshift			8			8
inframe indel			3			3
splice donor/acceptor (+/-2bp)		1	4			5
splice region			8	15	2	25
non coding			5	53	13	71
Total	1	1	220	151	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)
6-31946023-T-C		Atypical hemolytic-uremic syndrome with B factor anomaly • Macular degeneration	Uncertain significance (Jan 12, 2018)
6-31946032-CG-C		Macular degeneration • Atypical hemolytic-uremic syndrome	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 (Jun 16, 2023)
6-31946245-A-G			Likely benign (Jan 03, 2024)
6-31946247-T-A		Age related macular degeneration 14 • Macular degeneration • Complement component 2 deficiency • not specified • Atypical hemolytic-uremic syndrome • 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 • CFB-related disorder	Benign/Likely benign (Jan 29, 2024)
6-31946260-C-T			Likely benign (Feb 05, 2022)
6-31946269-G-A			Likely benign (Aug 01, 2023)
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 (Feb 26, 2021)
6-31946291-C-T		CFB-related disorder	Uncertain significance (Apr 30, 2023)
6-31946296-G-C			Likely benign (Aug 23, 2023)
6-31946304-C-G			Likely benign (Dec 11, 2023)
6-31946363-T-C			Likely benign (Oct 22, 2023)
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 • Atypical hemolytic-uremic syndrome with B factor anomaly;Complement factor b deficiency;Age related macular degeneration 14 • CFB-related disorder	Benign/Likely benign (Jan 31, 2024)
6-31946403-G-A		BF*FA/S • Factor B fast/slow polymorphism • Atypical hemolytic-uremic syndrome • Macular degeneration • Age related macular degeneration 14 • Complement component 2 deficiency • not specified • Atypical hemolytic-uremic syndrome with B factor anomaly • Complement component 2 deficiency;Age related macular degeneration 14 • Focal segmental glomerulosclerosis	Benign/Likely benign (Feb 01, 2024)
6-31946405-C-G			Uncertain significance (Jul 12, 2023)
6-31946418-G-A			Uncertain significance (Nov 23, 2022)
6-31946426-G-A		Atypical hemolytic-uremic syndrome with B factor anomaly	Uncertain significance (Oct 04, 2019)
6-31946426-G-C			Uncertain significance (Jun 06, 2021)

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