The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

Abstract

Communicated by A. Jamie CuticchiaWe 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. Hum Mutat 29(3), [351][352][353][354][355][356][357][358][359][360] 2008.

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

“…The importance of keratins for providing mechanical stress resilience in the epidermis is best documented by blistering and hyperkeratotic skin disorders exemplified by Epidermolysis bullosa simplex (EBS; OMIM #131900), caused by mutations in KRT5 and KRT14 (Szeverenyi et al 2008). EBS is characterized by cytoplasmic keratin aggregates, cytolysis of basal keratinocytes, and bullous lesions following mild trauma to the skin.…”

The molecular genetic analysis of the expanding pachyonychia congenita case collection

“…In five of these (families [16][17][18][19][20] mutations were at the intron 1/exon 2 boundary of K6a; three different sequence changes were identified, all of which we have reported previously, 16 but at that time, owing to the unavailability of mRNA, we were unable to identify the mutations at the protein level. However, in this study we obtained mRNA from a skin biopsy from an affected individual from family 17 with mutation K6a c.541-2A>G. The resulting cDNA was amplified by PCR and cloned, and several clones were sequenced to identify the consequence of this mutation.…”

“…17 Mutation K6a p.Glu473GlyfsTer91 (family 30), an unreported frameshift mutation at the end of the 2B domain of K6a, is due to duplication of a single 'G' nucleotide, c.1417dupG. This results in a frameshift starting with codon 473, which is changed from glutamic acid to a glycine residue and creates a premature stop codon at position 91 of the new reading frame; this is predicted to cause loss of normal protein function through protein truncation.…”

Investigating Cellular Nanoscale with X-rays

“…vimentin is found in fibroblasts, neurofilaments in neurons, or keratin in epithelial cells (section 1.4). The biomedical importance of studying IF proteins is high as many diseases involve IFs mutations [107,112,[179][180][181]. For example, the clumping of keratin IFs is involved in epidermolytic hyperkeratosis.…”