Annotation of functional impact of voltage-gated sodium channel mutations.
Voltage-gated sodium channels are pore-forming transmembrane proteins that selectively allow sodium ions to flow across the plasma membrane according to the electro-chemical gradient thus mediating the rising phase of action potentials in excitable cells and playing key roles in physiological processes such as neurotransmission, skeletal muscle contraction, heart rhythm, and pain sensation. Genetic variations in the nine human genes encoding these channels are known to cause a large range of diseases affecting the nervous and cardiac systems. Understanding the molecular effect of genetic variations is critical for elucidating the pathologic mechanisms of known variations and in predicting the effect of newly discovered ones. To this end, we have created a Web-based tool, the Ion Channels Variants Portal, which compiles all variants characterized functionally in the human sodium channel genes. This portal describes 672 variants each associated with at least one molecular or clinical phenotypic impact, for a total of 4,658 observations extracted from 264 different research articles. These data were captured as structured annotations using standardized vocabularies and ontologies, such as the Gene Ontology and the Ion Channel ElectroPhysiology Ontology. All these data are available to the scientific community via neXtProt at https://www.nextprot.org/portals/navmut.
CALIPHO Group, SIB Swiss Institute of Bioinformatics, Geneva, Switzerland.
Valérie
V
Hinard
CALIPHO Group, SIB Swiss Institute of Bioinformatics, Geneva, Switzerland.
Aurore
A
Britan
CALIPHO Group, SIB Swiss Institute of Bioinformatics, Geneva, Switzerland.
Mathieu
M
Schaeffer
CALIPHO Group, SIB Swiss Institute of Bioinformatics, Geneva, Switzerland.
Monique
M
Zahn-Zabal
Institute of Biochemistry and Molecular Medicine, Bern, Switzerland.
Urs
U
Thomet
Institute of Biochemistry and Molecular Medicine, Bern, Switzerland.
Jean-Sébastien
JS
Rougier
Department of Human Protein Science, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Amos
A
Bairoch
Institute of Biochemistry and Molecular Medicine, Bern, Switzerland.
Hugues
H
Abriel
CALIPHO Group, SIB Swiss Institute of Bioinformatics, Geneva, Switzerland.|Department of Human Protein Science, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Pascale
P
Gaudet
D000818:Animals; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D055724:Electrophysiological Phenomena / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D058977:Molecular Sequence Annotation; D009154:Mutation; D010641:Phenotype; D000072417:Protein Domains; D012720:Severity of Illness Index; D012984:Software; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D064878:Web Browser
D061566:Voltage-Gated Sodium Channels
clinical interpretation of variants; databases; genetics variants; pathogenicity; phenotype; voltage-gated sodium channel