ABSTRACT In the mid-1990s, a database was established to keep track of an increasing number of variants in human Cytochrome P450 genes shown to be responsible for a wide range of activity towards numerous clinically used drugs. An international group of leading experts had also devised a star (*) nomenclature system to organize haplotypes in a systematic way which has readily been adopted by the vast majority of pharmacogenetic/genomic professionals. The has become the primary resource and sole authority for issuing allele Human Cytochrome P450 (CYP) Allele Nomenclature Database definitions. The internationally renowned Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC), are among the many endeavors relying on the current CYP nomenclature web site. Dr Ingelman-Sundberg will no longer be in a position to run the site in the future. In this proposal we outline a plan for the Pharmacogene Variation (PharmVar) Consortium. This consortium will serve as a centralized `Next-Generation' Pharmacogene Variation data repository to empower PharmGKB to disseminate nomenclature information. The current content of the nomenclature resource will be transitioned to the PharmGKB and curated for accuracy allowing the content to be accessible to the community after the original site ceases to exist. A basic version of the PharmVar database is being built and populated with high-priority pharmacogenes (i.e. clinically actionable CPIC genes) and will be expanded in functionality and content under the current proposal. Highlights include a transparent submission and review process, versioning at a haplotype, gene and database level and annotations. New functionality will be built into the PharmGKB to disseminate haplotypes for which functional information is available. We will also build an application programming interface (API) to enable data flow to/from PharmVar and the PharmGKB. Pharmacogene variation data in PharmVar will be directly accessible to users. To maximize utility of the PharmVar, we will closely work with CPIC and through our collaboration with the PharmGKB seek collaborations with other databases to unify and standardize pharmacogene variation designation and translation into phenotype. The PharmVar and PharmGKB teams bring rich expertise and existing collaborations to the proposed plan, which are essential components for advancing genome-informed medicine and pharmacogenetically-guided individualized drug therapy at large.

PROJECT NARRATIVE In this proposal we outline a plan for a Pharmacogene Variation (PharmVar) Consortium that will establish a critical resource for researchers and clinical professionals. The PharmVar Consortium will serve as a central repository for information facilitating the interpretation of pharmacogenetic test results to guide individualized drug therapy.