New look Gene2Phenotype website
Gene2Phenotype (G2P) disseminates gene-disease models, curated from the literature by domain experts. It has now been extended to support more detailed gene-disease mechanisms and variant information, and the website has been updated to have a fresh new look.
Clinical geneticists require the latest high-quality, detailed gene-disease association information to enable diagnostic variant filtering. G2P was established in 2012 by David FitzPatrick (a consultant in paediatric genetics) to meet this need and accelerate the diagnosis of children with developmental disorders. In 2014, the database moved from the University of Edinburgh to EMBL-EBI and was generalised to cover other disease areas.
G2P has now been extended to capture the mechanism by which disease occurs (e.g. ‘loss of function’, ‘dominant negative’), a more detailed categorisation, where available (e.g. ‘assembly-mediated GOF’, ‘loss of activity LOF’), and the types of functional studies supporting the mechanism assertion. Understanding disease mechanisms is important for clinical diagnosis and for the development of molecular therapies which are designed to correct detrimental cellular processes. It is also essential for the application of multiplex assay of variant effect results to clinical variant interpretation.
G2P records the mechanism by which genes are involved in disease. This enables diagnostic filtering to prioritise any variants predicted to trigger the same mechanism on the affected gene. For some disorders, the same variants are observed multiple times and in some cases only specific variants or regions are involved in disease. Specific variant information is now also captured to support these cases.
G2P data is incorporated into other resources including OpenTargets, Ensembl and PanelApp. To enable improved linking, individual G2P records are now assigned stable identifiers. These G2P identifiers can be used to build predicted URLs to record pages.
Conventions for disease naming have evolved since G2P was established. All disease names have now been standardised to use the dyadic format. Records can still be retrieved by searching on previously used disease names.
More information
Thormann, A., et al. Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun 10, 2373 (2019). https://doi.org/10.1038/s41467-019-10016-3
Yates,T.M., et al. Curating genomic disease-gene relationships with Gene2Phenotype (G2P). Genome Med 16, 127 (2024). https://doi.org/10.1186/s13073-024-01398-1.
