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UniProtKB/Swiss-Prot P00751: Variant p.Phe286Leu

Complement factor B
Gene: CFB
Variant information

Variant position:  286
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Phenylalanine (F) to Leucine (L) at position 286 (F286L, p.Phe286Leu).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and aromatic (F) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In AHUS4; gain-of-function mutation that results in enhanced formation of the C3bBb.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  286
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  764
The length of the canonical sequence.

Location on the sequence:   SGSMNIYLVLDGSDSIGASN  F TGAKKCLVNLIEKVASYGVK
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SGSMNIYLVLDGSDSIGASNFTGAKKCLVNLIEKVASYGVK

Gorilla                       SGSMNIYLVLDGSDSIGASNFTGAKKCLVNLIEKVASYGVK

Chimpanzee                    SGSMNIYLVLDGSDSIGASNFTGAKKCLVNLIEKVASYGVK

Mouse                         SGSMNIYLVLDGSDSIGSSNFTGAKRCLTNLIEKVASYGVR

Bovine                        SGSMNIYLVLDGSDSVGAHNFTGAKNCLRDFIEKVASYGVK

Slime mold                    --------------------------CLI------------

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 26 – 764 Complement factor B
Chain 260 – 764 Complement factor B Bb fragment
Domain 270 – 469 VWFA
Glycosylation 285 – 285 N-linked (GlcNAc...) asparagine
Glycosylation 291 – 291 N-linked (Glc) (glycation) lysine
Helix 283 – 301


Literature citations

Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.
Goicoechea de Jorge E.; Harris C.L.; Esparza-Gordillo J.; Carreras L.; Arranz E.A.; Garrido C.A.; Lopez-Trascasa M.; Sanchez-Corral P.; Morgan B.P.; Rodriguez de Cordoba S.;
Proc. Natl. Acad. Sci. U.S.A. 104:240-245(2007)
Cited for: VARIANTS AHUS4 LEU-286 AND GLU-323; CHARACTERIZATION OF VARIANTS AHUS4 LEU-286 AND GLU-323;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.