PAHdb: A locus-specific mutation
knowledgebase focusing on their associations and effects
PAHdb is an online relational locus-specific database (http://www.pahdb.mcgill.ca)
for mutations in the human phenylalanine hydroxylase gene (symbol PAH)
and the associated phenotypes at the levels of protein, metabolites and
organism. When combined with information about associations of mutations with
populations, haplotypes and other features, PAHdb operates as a knowledge
base. PAHdb is disease-oriented for hyperphenylalaninemia (HPA) (see OMIM
261600) due to primary deficiency of PAH enzyme function (EC
18.104.22.168). PAHdb and its numerous modules are, in practice, maintained
by a team of curators who follow guidelines for nomenclature (Antonarakis et al.
Hum Mutat 11:1-3, 1998; Human Gene Nomenclature Committee: http://www.gene.ucl.ac.uk/nomenclature),
and for content, design and deployment (Scriver et al. Hum Mutat
13:344-350, 1999). PAHdb accepts and validates direct online submissions
of mutation and auxiliary information. Content of PAHdb includes the cDNA
U49897.1) and the genomic sequence (GenBank
AF404777). All alleles have the appropriate context (species, locus, gene,
unique identifier number, name and source of information); are identifiable by
the SRS search engine and are recognizable as either pathogenic (phenotype
modifying) or polymorphic (putatively neutral in effect). A platform for
molecular modeling shows a crystal structure and amino acid residues at 2.0 Å
resolution. Separate tables provide results of In Vitro Expression
analysis; 57 naturally occurring human PAH alleles (109 records); 24
artificial rat PAH alleles (25 records); 6 artificial human alleles.
Human genotype/phenotype correlations are available for a large number of
mutations; raw data are stored in a repository accessible from the main page.
Genetic models of HPA in the mouse are described in a separate module. Another
module provides clinical information on HPA for patients and students, and about
its treatment, with pointers to resources. A Curators' Page comments
occasionally on relevant articles which cannot easily be deconstructed for entry
into the database.