Fig. 4

Gene similarity approach. a Genes sharing features with BIEM genes for each category of EL genes based on evidence for the gene-disease association. Each set of EL genes in the mouse (assessed and predicted) is broken down into 3 sub-categories based on PanelApp evidence: genes associated with inborn errors of the metabolism, Mendelian disease genes in other disease categories and non-disease genes. For genes in PanelApp panels, the genes are also subdivided into those with strong evidence for the gene-disease association (green) and those with more limited evidence to date (red or amber). The percentage of genes sharing one of the 5 features (paralogue, protein family, ppi, pathway, protein complex) with known BIEM genes is shown for potential novel genes absent from PanelApp as well as those with more limited evidence (red or amber). For each sub-category, those genes sharing ≥4 features with known BIEM genes are shown. Nine assessed and 5 predicted EL genes that are included in this figure as amber/red genes in the IEM panel are also green genes in other disease panels (see Files S3-S4 [33]). b PRMT1 IMPC mouse evidence. Mouse phenotypes and phenotypic similarity with human disorders. Heterozygous knockout phenotypes include several metabolic and neurological abnormalities. When computing the similarity between the mouse and human disease phenotypes associated with known disorders, we find phenotypic overlap with several early onset conditions, including defects of the metabolism coenzyme Q10 deficiency, primary, 8 and hypoxanthine guanine phosphoribosyltransferase partial deficiency. EL, early gestation lethal; BIEM, biallelic inborn errors of the metabolism; ppi, protein-protein interaction; IMPC, International Mouse Phenotyping Consortium