mutagenecity prediction; ion channels; disease variants; channelopathies; biocuration
Hinard Valérie, Britan Aurore, Schaeffer Mathieu, Zahn-Zabal Monique, Thomet Urs, Rougier Jean-SébastienS, Bairoch Amos, Abriel Hugues, Gaudet Pascale (2017), Annotation of functional impact of voltage-gated sodium channel mutations, in Human Mutation
, 38(5), 485-493.
Hinard Valérie, Britan Aurore, Rougier Jean-Sebastien, Bairoch Amos, Abriel Hugues, Gaudet Pascale (2016), ICEPO: the Ion Channel ElectroPhysiology Ontology, in Database (Oxford).
, baw017, 1-7.
Thousands of mutations in human genes coding for ion channel subunits cause channelopathies such as epilepsy, migraine, paralysis, and cardiac arrhythmias. This research project integrates high-quality knowledge resources, state of the art bioinformatics tools and laboratory experiments. As a first step, it focusses on the family of voltage-gated sodium channels (Navs). In the framework of this proposal we will produce a comprehensive corpus of annotations on the pathogenic effect of known sequence variations in the nine human genes coding for Navs. We will take advantage of the high-level of sequence conservation that is the hallmark of this family of ion channels to produce a new web-based bioinformatics tool, NavMutPredict. Our aim is to make use of all pertinent knowledge on the mutations in the Navs and on their biophysical properties so as to predict the effect, in particular its pathogenicity, of newly discovered genetic variation. The integration of the prediction tool with the laboratory characterization of Navs mutations will allow the validation of this new prediction tool so as to make it useful in a clinical context. We also expect that the methodologies developed in this proposal can later be applied to other families of ion channels so as to address the whole spectrum of channelopathies.