We describe a revised and expanded database on human intermediate filament 
proteins, a major component of the eukaryotic cytoskeleton. The family of 70 
intermediate filament genes (including those encoding keratins, desmins, and 
lamins) is now known to be associated with a wide range of diverse diseases, at 
least 72 distinct human pathologies, including skin blistering, muscular 
dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative 
disorders, and cataract. To date, the database catalogs 1,274 manually-curated 
pathogenic sequence variants and 170 allelic variants in intermediate filament 
genes from over 459 peer-reviewed research articles. Unrelated cases were 
collected from all of the six sequence homology groups and the sequence 
variations were described at cDNA and protein levels with links to the related 
diseases and reference articles. The mutations and polymorphisms are presented 
in parallel with data on protein structure, gene, and chromosomal location and 
basic information on associated diseases. Detailed statistics relating to the 
variants records in the database are displayed by homology group, mutation type, 
affected domain, associated diseases, and nucleic and amino acid substitutions. 
Multiple sequence alignment algorithms can be run from queries to determine DNA 
or protein sequence conservation. Literature sources can be interrogated within 
the database and external links are provided to public databases. The database 
is freely and publicly accessible online at www.interfil.org (last accessed 13 
September 2007). Users can query the database by various keywords and the search 
results can be downloaded. It is anticipated that the Human Intermediate 
Filament Database (HIFD) will provide a useful resource to study human genome 
variations for basic scientists, clinicians, and students alike.