This report describes combined oxidative phosphorylation deficiency 1 (COXPD1); COXPD1 exhibits autosomal recessive inheritance. The human gene implicated in this disease is the nuclear-encoded mitochondrial elongation factor G1 (GFM1). Over 30 genes in human have been implicated in subtypes of combined oxidative phosphorylation deficiency; see the OMIM phenotypic series for this disease (https://www.omim.org/phenotypicSeries/PS609060). There is a single Drosophila gene, mEFG1, orthologous to human GFM1; in each species there is a second paralogous gene (human GMF2 and Dmel\mRRF2). Classical loss-of-function mutations, RNAi-targeting constructs, and loss-of-function alleles caused by imprecise excisions of a TE insertion have been generated for Dmel\mEFG1.
Multiple UAS constructs of the human Hsap\GFM1 gene have been introduced into flies, including wild-type and constructs carrying disease-implicated variants. Heterologous rescue (functional complementation) has been demonstrated for the lethal phenotype of Dmel\mEFG1 loss-of-function mutations. Variant(s) implicated in human disease tested (as transgenic human gene, GFM1): the N174S and S321P variant forms have been introduced into flies. Based on the capacity of both the human missense mutations to mediate some degree of rescue, S321P is postulated to result in a more severe loss of function than N174S.
Animals homozygous for amorphic mutations of Dmel\mEFG1 typically die in the larval stage. In contrast, missense mutations exhibit stronger, possibly neomorphic phenotypes that lead to death earlier, during embryogenesis.
[updated Feb. 2019 by FlyBase; FBrf0222196]
Combined oxidative phosphorylation deficiency is an autosomal recessive multisystem disorder with variable manifestations resulting from a defect in the mitochondrial oxidative phosphorylation (OXPHOS) system. Onset occurs at or soon after birth, and features can include growth retardation, microcephaly, hypertonicity, axial hypotonia, encephalopathy, cardiomyopathy, and liver dysfunction. Death usually occurs in the first weeks or years of life (summary by Smits et al., 2011; pubmed:21119709). [from MIM:609060; 2021.04.17]
[COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 1; COXPD1](https://omim.org/entry/609060)
[MITOCHONDRIAL ELONGATION FACTOR G1; GFM1](https://omim.org/entry/606639)
Combined oxidative phosphorylation deficiency-1 (COXPD1) is caused by homozygous or compound heterozygous mutation in the gene encoding the mitochondrial elongation factor G1 (GFM1). [from MIM:609060; 2019.02.14]
In mitochondria, the protein translation elongation phase requires 3 elongation factors, one of which is GFM1. [from MIM:606639; 2019.02.14]
One to one: 1 human to 1 Drosophila; a second paralgous gene exists in both species. (Human GRM2 is much more closely related to Drosophila mRRF2.)
High-scoring ortholog of human GFM1 (1 Drosophila to 1 human); a second paralgous gene exists in both species. Dmel\mEFG1 shares 66% identity and 79% similarity with the human GFM1 gene.
