| URL: | http://www.fh-hus.org |
| Full name: | FH aHUS Mutation Database |
| Description: | This database integrates genotypic, phenotypic, and structural information for mutations within human factor H. There are now a total of 167 genetic alterations, including 100 in CFH, 43 in MCP, and 24 in IF. |
| Year founded: | 2006 |
| Last update: | 2018 |
| Version: | |
| Accessibility: |
Accessible
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| Country/Region: | United Kingdom |
| Data type: | |
| Data object: | |
| Database category: | |
| Major species: | |
| Keywords: |
| University/Institution: | University College London |
| Address: | Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Darwin Building, University College London, London, United Kingdom. |
| City: | London |
| Province/State: | |
| Country/Region: | United Kingdom |
| Contact name (PI/Team): | Saunders RE |
| Contact email (PI/Helpdesk): | s.perkins@medsch.ucl.ac.uk |
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The interactive Factor H-atypical hemolytic uremic syndrome mutation database and website: update and integration of membrane cofactor protein and Factor I mutations with structural models. [PMID: 17089378]
Atypical hemolytic uremic syndrome (aHUS) is a disease of hemolytic anemia, thrombocytopenia, and renal failure associated with defective alternative pathway (AP) complement control. Previously, we presented a database (www.FH-HUS.org) focusing on aHUS mutations in the Factor H gene (CFH). Here, new aHUS mutations are reported for the complement regulatory proteins Factor H (FH), Factor I (FI), and membrane cofactor protein (MCP). Additional mutations or polymorphisms within CFH have been associated with membranoproliferative glomerulonephritis (MPGN) and age-related macular degeneration (AMD). Accordingly, the database now includes substitutions that predispose to aHUS, MPGN, and AMD. For this, structural models for the domains in MCP and FI were developed using homology modeling. With this new database, patients with mutations in more than one gene can be displayed and interpreted in a coherent manner. The database also includes SNP polymorphisms in CFH, MCP, and IF. There are now a total of 167 genetic alterations, including 100 in CFH, 43 in MCP, and 24 in IF. The mutations characterize clinical outcomes that vary from several AMD-associated polymorphisms to those associated with aHUS, MPGN, or FI deficiency. A consensus short complement regulator (SCR) domain structure facilitated the interpretations of aHUS mutations. Specific locations within this consensus domain often correlate with the occurrence of clinical phenotypes. The AMD Tyr402His polymorphism is structurally located at a hotspot for several aHUS mutations. The database emphasizes the causative role of the alternative pathway of complement in disease and provides a repository of knowledge to assist future diagnosis and novel therapeutic approaches. |
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A user's guide to the interactive Web database of factor H-associated hemolytic uremic syndrome. [PMID: 16575691]
Atypical hemolytic uremic syndrome (aHUS) mutations have been reported in the complement regulatory proteins factor H, factor I, and membrane cofactor protein (MCP). Mutations within factor H are also associated with membranoproliferative glomerulonephritis and age-related macular degeneration. The increasing amount of information on aHUS requires organization if it is to be usable. Accordingly, an interactive factor H aHUS Web database has been developed (http://www.fh-hus.org) that integrates genotypic, phenotypic, and structural information for mutations within human factor H. This provides a valuable tool for the interpretation of previously reported aHUS mutations, and provides prediction and analysis tools for new mutations. It will be extended to include mutations in factor I and MCP. Here, we describe how to use this Web database as a research tool, and indicate possible future directions depending on feedback from the clinical community. |