Genetic modifiers can affect the penetrance, dominance, expressivity and pleiotropy of disease-causing mutations. Evidence for modifiers is extensive, both in humans and model organisms, and their effects on the phenotypic presentation of disease causing variants can be subtle or profound. Knowledge of human genetic modifiers is important for clinical phenotyping and research. However, systematic resources of genetic modifiers are rare. As the first systematic database of human genetic modifiers, PhenoModifier will facilitate the elucidation of the genetic basis of human phenotypic variation.
From clinical observations to large-scale NGS studies, the impact of genetic modifiers is evident, however, the concepts of their protection against disease and maintenance of health have been largely neglected in genetic testing. The PhenoModifier is aimed at providing a comprehensive summary of human genetic modifiers in order to guide clinical decision as well as the research community with a full spectrum of genetic contribution to disease risk.
The PhenoModifier is a database of manually curated human genetic modifiers extracted from the scientific literature. Only studies published in peer reviewed journals are considered for inclusion into the database. The database is being continually updated.
The public user interface of PhenoModifier allows three types of intuitive searching for modifier associated information: Querying whether a disordermay be affected by a modifier or modifiers, querying whether a gene contains any modifier variants, and querying whether a variant may function as a modifier. The search results will return comprehensive details about the modifier-related information. The home page provides a quick search utility which can be used to search the database for all the three types of queries.
Querying on the disorder page, users can search PhenoModifier by entering a disorder name, or select a disorder item from the list. The result page contains brief information on the disorder and provides links to external resources including Human Disease Ontology, OMIM and the Human Phenotype Ontology database. The result page displays a detailed table of the modifier genes that may affect the variability of the disorder. By clicking on the hyperlink on a modifier gene, users can obtain more detailed information including the gene information, its potential interacting partners, variants of the modifier gene, publication information etc. By clicking on the hyperlink of a variant, users can obtain more detailed information including variant information, target disorder, publication (i.e. title, abstract, PubMed ID), etc.
Querying on the gene page, users can search PhenoModifier by entering a gene name or by entering a list of genes, either gene symbol, Ensembl gene ID or NCBI gene ID. The result page contains brief information on the gene and provides links to external resources. The result page displays a detailed table of the potential partners with which the modifier gene may interact and a detailed table showing the modifier variants in the gene and publication information etc. Batch genes query retrieves detailed information about which genes may function as modifiers.
Querying on the variant page, users can search PhenoModifier by entering a variant name or by entering a list of variants, either refSNP(rs) number or HGVS variant name. The result page contains brief information on the variant and provides links to external resources dbSNP. The result page displays detailed information including the target disorder, publication information etc. Batch variants query retrieves detailed information about which variants may function as modifiers.
PhenoModifier content statistics (v1.003 Sep 23, 2019)