The overall biological function of a protein is commonly governed by the various combinations of protein domains within it [Peterson et al., 2010]. Therefore, we annotate the potential molecular and phenotypic consequences of pathogenic mutations via domain-centric ontologies [de Lima Morais et al., 2011]. For example, the molecular consequences of AASs are statistically inferred by mapping SUPERFAMILY [Gough et al., 2001] HMMs onto the Gene Ontology [Ashburner et al., 2000]. Moreover, the phenotypic consequences of AASs are annotated by extending these mappings onto several phenotype ontologies including the Human Phenotype Ontology [Robinson et al., 2008], the Mammalian Phenotype Ontology [Smith and Eppig, 2009] and the Plant Phenotype Ontology [Ilic et al., 2007; Pujar et al., 2006].
