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Fabry disease (MIM 3010500) is an X-linked genetic disease resulting from a deficiency of α-galactosidase A (GLA, EC 3.2.1.22), and exhibits a wide clinical spectrum, from the early-onset severe ‘classic’ form to the late-onset mild ‘variant’ one.1 Recently, the results of newborn screening revealed that the incidence of Fabry disease is unexpectedly high,2, 3, 4 and that the genotypes of patients with this disease are quite heterogeneous.5

Previously, we constructed structural models of mutant GLAs resulting from 161 Fabry missense mutations, and examined the correlation between structural changes in GLA and the clinical and biochemical phenotypes of Fabry disease.6 Recently, we conducted further structural investigation on Fabry disease using a structural analysis system and revealed that structural changes in GLA are very important for understanding the molecular basis of this disease.5

To the best of our knowledge, there is no database including the structures of mutant GLAs. In order to help researchers and clinicians who study Fabry disease, we built a database of clinical phenotypes, genotypes and structures of mutant GLAs. This database can be accessed as ‘fabry-database.org’, and is user-friendly, being equipped with powerful computational tools like Jmol, which is an open-source Java viewer for chemical structures in 3D (http://www.jmol.org). The web interface and applications are shown in Supplementary Information S1.

Fabry-database.org contains (i) comprehensive information on GLA mutations, (ii) tools for three-dimensional structure visualization and (iii) tools to search for GLA mutations. A total of 504 unique GLA mutations have been incorporated into the database so far. The GLA mutation statistics and the data structure of fabry-database.org are shown in Table 1 and Supplementary Information S2, respectively.

Table 1 Gene mutations causing Fabry disease
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Several tools have been equipped within the database to enhance its scope. The following are the main web tools integrated into fabry-database.org (Figure 1). A text search tool is provided for searching selected fields of the database. A control table option is incorporated for an intensive search. Using this option, users can search for Fabry mutations that are connected with specific phenotypes. Fabry-database.org allows users to display the three-dimensional structures of molecules using Jmol. Users are provided with many options for visualizing the structures of mutant GLAs. Figure 2 represents the pages concerning the structure of a mutant GLA with the T100R amino-acid substitution, as an example. As a structural change in GLA should be related to genotype expression and the outcome of Fabry disease,5, 6 this database will help researchers and clinicians.

Figure 1
figure 1

List of Fabry mutations.

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Figure 2
figure 2

Structure: color imaging of the T100R mutation by means of the solvent-accessible surface area.

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The major limitation for expanding this database is that the information on Fabry mutations is too scattered. A lot of literature search is required to further expand it. In the near future, we are hopeful of expanding the database quantitatively to cover all possible amino-acid mutations. This database will be updated manually as soon as enough data become available.

In conclusion, we constructed fabry-database.org, which is available at http://www.fabry-database.org. To access fabry-database.org, the World Wide Web access is a prerequisite. For using all the features of fabry-database.org optimally, plugging in the JavaScript and Java Runtime Environment must be enabled.