Fig. 5

Candidate genes with biallelic inheritance involving LoF or (missense) predicted pathogenic variants in undiagnosed patients. a Mouse evidence. Genes with homozygous LoF or missense variants found in patients recruited under the ‘undiagnosed metabolic disorder’ and ‘mitochondrial disorders’ disease categories with an OE ratio > 1, observed in ≤ 2 controls and with the IMPC heterozygous knockout mouse displaying abnormal phenotypes in the relevant physiological systems, partially mimicking the phenotypes observed in patients. b COQ3 and CDK12 belong to families and pathways with several genes associated with Mendelian disorders. The corresponding mode of inheritance and related/overlapping phenotypes for these known disease associated genes and evidence on viability from the IMPC are shown. Information on prioritised genes available in File S4 [33]. LoF, loss-of-function; OE, observed vs expected; IMPC, International Mouse Phenotyping Consortium; AD, autosomal dominant; AR, autosomal recessive