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FB2026_01
,
released March 12, 2026
This report describes mitochondrial DNA depletion syndrome 6 (hepatocerebral type), an autosomal recessive subtype of mitochondrial DNA depletion syndrome. The human gene implicated is MPV17, which encodes a mitochondrial inner membrane protein involved in mitochondrial deoxynuclueotide homeostasis and maintenance of mitochondrial DNA. There is one high-scoring Drosophila ortholog, Dmel\Mpv17, for which RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. MPV17 has also been been implicated in Charcot-Marie-Tooth disease, axonal, type 2EE (MIM:618400, FBhh0001499).
A tagged wild-type UAS construct of the human gene, Hsap\MPV17 has been introduced into flies.
Pan-neuronal RNAi-mediated targeted knockdown of Dmel\Mpv17 results in deficits in learning and locomotive behavior, impairs mitochondrial function in the larval CNS, and induces abnormal morphology in the larval neuromuscular junction.
[updated Nov. 2022 by FlyBase; FBrf0222196]
Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues without mutations or rearrangements in the mtDNA. MDS is phenotypically heterogeneous, and can affect a specific organ or a combination of organs, with the main presentations described being either hepatocerebral (i.e. hepatic dysfunction, psychomotor delay), myopathic (i.e. hypotonia, muscle weakness, bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). [http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=35698.0 2016.11.23]
[MITOCHONDRIAL DNA DEPLETION SYNDROME 6 (HEPATOCEREBRAL TYPE); MTDPS6](https://omim.org/entry/256810)
[MITOCHONDRIAL INNER MEMBRANE PROTEIN MPV17; MPV17](https://omim.org/entry/137960)
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) (MTDPS6) is an autosomal recessive disorder characterized by infantile onset of progressive liver failure, often leading to death in the first year of life. Those that survive develop progressive neurologic involvement, including ataxia, hypotonia, dystonia, and psychomotor regression (Spinazzola et al., 2008, pubmed:18695062). [from MIM:256810; 2023.02.23]
MTDPS6 is caused by homozygous or compound heterozygous mutation in the MPV17 gene on chromosome 2p23. [from MIM:256810; 2023.02.23]
Sural nerve biopsy showed nearly complete absence of myelinated fibers without evidence of regeneration, and degenerative unmyelinated fibers with evidence of regeneration (Appenzeller et al., 1975, pubmed:185990). [from MIM:256810; 2023.02.23]
Non-selective channel that modulates the membrane potential under normal conditions and oxidative stress, and is involved in mitochondrial homeostasis (Antonenkov, et al., 2015, pubmed:25861990). Involved in mitochondrial deoxynucleoside triphosphates (dNTP) pool homeostasis and mitochondrial DNA (mtDNA) maintenance (Dalla Rosa, et al., 2016, pubmed:26760297). May be involved in the regulation of reactive oxygen species metabolism and the control of oxidative phosphorylation. [from Uniprot:P39210; 2023.02.22]
The MPV17 gene encodes a mitochondrial inner membrane protein that is involved in mitochondrial deoxynucleotide homeostasis and maintenance of mtDNA (summary by Baumann et al., 2019). [from MIM:137960; 2023.02.23]
One to one (1 human to 1 Drosophila); MPV17 has one high-scoring Drosophila ortholog, Mpv17.
High-scoring ortholog of human MPV17(1 Drosophila to 1 human).