This report describes combined oxidative phosphorylation deficiency 28 (COXPD28); COXPD28 exhibits autosomal recessive inheritance. The human gene implicated in this disease is SLC25A26, which encodes a mitochondrial solute carrier involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. There is a single orthologous gene in Drosophila, CG4743, for which an amorphic mutation, RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human SLC25A26 gene has not been introduced into flies.
Animals carrying an amorphic mutation of CG4743 die in the larval stage; metabolic changes consistent with deficiency or reduction of mitochondrial S-adenosylmethionine (mitoSAM) are observed. Mutations in the fly gene analogous to those implicated in COXPD28 have been characterized. Variant(s) implicated in human disease introduced (as analogous mutation in fly gene): A123V in the fly CG4743 gene (corresponds to A102V in the human SLC25A26 gene); I172G in the fly CG4743 gene (corresponds to V148G in the human SLC25A26 gene); P223L in the fly CG4743 gene (corresponds to P199L in the human SLC25A26 gene).
[updated Apr. 2021 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 28; COXPD28](https://omim.org/entry/616794)
[SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER, PHOSPHATE CARRIER), MEMBER 26; SLC25A26](https://omim.org/entry/611037)
Combined oxidative phosphorylation deficiency-28 (COXPD28) is a complex autosomal recessive multisystem disorder associated with mitochondrial dysfunction. The phenotype is variable, but includes episodic metabolic decompensation beginning in infancy that can result in mild muscle weakness, cardiorespiratory insufficiency, developmental delay, or even death. Biochemical studies of patient tissues show variable mitochondrial defects, including decreased activities of respiratory chain enzymes (summary by Kishita et al., 2015; pubmed:26522469). [from MIM:616794; 2021.04.17]
Combined oxidative phosphorylation deficiency-28 (COXPD28) is caused by homozygous or compound heterozygous mutation in the SLC25A26 gene. [from MIM:616794; 2021.04.17]
SLC25A26 encodes a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. [Gene Cards, SLC25A26; 2021.04.17]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human SLC25A26 (1 Drosophila to 1 human). Dmel\CG4743 shares 52% identity and 65% similarity with the human gene.
