Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Complement factor B

The CFB gene encodes a stimulating factor to the alternative complement pathway. Gain-of-function mutations have been described in atypical HUS and age-related macula degeneration.

Protein Structure

The N-terminal fragment, Ba, is released during activation. It is composed of three complement control protein (CCP) domains. The active fragment Bb attains a dumbbell shape, and consists of two domains, one on each side. The N-terminal is a von Willebrand factor type A (vWFA) domain, and the C-terminal domain is a serine protease (SP). The vWFA domain (202 residues) shows structural similarities to the I domain of integrins. This domain contains a motif called Mg ion-dependent adhesion site (MIDAS), which is supposed to take part in C3b binding and SP activation. The Asn residue at codon position 260 is glycosylated. The SP domain consists of 283 residues. The proteolytic site is opposite the MIDAS motif.[Error: Macro 'ref' doesn't exist]

Expression

Before activation, factor B circulates in the blood as a single polypeptide chain.

Gene Regulation

Nativ Factor B is cleaved and activated by Factor D when bound to C3b. Ba is released, and the remaining complex C3bBb is a proficient C3-convertase that accelerates C3 activation by a positive feedback loop. The complex C3bBb is inherently unstable and easily dissociates. This inactivation is promoted by MCP, CFH, and CFI.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Hemolytic-Uremic Syndrome
ADAMTS13
C3
C4BPA
C4BPB
CD46
CFB
CFH
CFHR1
CFHR2
CFHR3
CFHR4
CFHR5
CFI
CLU
DGKE
Methylmalonic aciduria
Methylmalonic aciduria and homocystinuria cblC
MMACHC
Methylmalonic aciduria and homocystinuria cblD
MMADHC
Methylmalonic aciduria type mut
MUT
PIGA
PLG
THBD
Meningococcal infection susceptibility
C3
C5
C7
C8A
C8B
C8G
C9
CD46
CFB
CFD
CFH
CFP

References:

1.

Nürnberger J et al. (2009) Eculizumab for atypical hemolytic-uremic syndrome.

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2.

Zheng XL et al. (2008) Pathogenesis of thrombotic microangiopathies.

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3.

Maller J et al. (2006) Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration.

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4.

Ponnuraj K et al. (2004) Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.

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5.

Kavanagh D et al. (2006) Does complement factor B have a role in the pathogenesis of atypical HUS?

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6.

Gold B et al. (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.

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7.

Goicoechea de Jorge E et al. (2007) Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.

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8.

Wyatt RJ et al. (1981) Properdin deficiency with IgA nephropathy.

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9.

Orphanet article

Orphanet ID 158379 [^]
10.

NCBI article

NCBI 629 [^]
11.

OMIM.ORG article

Omim 138470 [^]
12.

Wikipedia article

Wikipedia EN (Complement_factor_B) [^]
Update: April 29, 2019