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MPV17
mitochondrial inner membrane protein MPV17
The MPV17 gene encodes a mitochondrial inner membrane protein believed to be vital for the maintenance of mitochondrial DNA (mtDNA), which is critical for cellular energy production. The MPV17 gene provides instructions for a protein located in the inner membrane of mitochondria.
MPV17 is located on the short (p) arm of chromosome 2, at band 2p23.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The MPV17 gene encodes a protein found within the inner membrane of mitochondria, which are cellular organelles responsible for a wide range of essential activities including energy generation. While its precise function is still under investigation, the MPV17 protein is understood to play a role in maintaining mitochondrial DNA (mtDNA). Adequate levels of mtDNA are fundamental for normal energy production within cells.
Inherited pathogenic variants in the MPV17 gene are associated with autosomal recessive conditions, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to be affected.
What the gene does
The MPV17 gene provides instructions for making a protein located in the inner membrane of mitochondria. Mitochondria are central to cellular metabolism, involved in energy production, chemical signalling, and the regulation of cell growth and division. These organelles contain their own DNA, known as mitochondrial DNA (mtDNA), which is essential for their normal function. While the exact mechanisms are not fully elucidated, the MPV17 protein is believed to be involved in the critical maintenance of mtDNA. Maintaining sufficient amounts of mtDNA is crucial for cells to produce energy effectively. Dysfunction of the MPV17 protein can lead to a reduction in mtDNA levels, impairing mitochondrial function and leading to a variety of health issues, particularly affecting tissues with high energy demands like the liver and brain.
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Chromosome location
The MPV17 gene is situated on chromosome 2, specifically at position 2p23.3. This location indicates its position on the short (p) arm of chromosome 2.
Protein structure
The MPV17 protein consists of 176 amino acid residues. Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants in the MPV17 gene can alter the protein's function, potentially leading to reduced mitochondrial DNA maintenance. More than 30 different pathogenic variants have been identified in the MPV17 gene, many of which involve single amino acid changes within the protein sequence. These variants can impair the protein's ability to support mitochondrial health.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.284delG | - | Pathogenic/Likely pathogenic | ★★☆☆ | Mitochondrial DNA depletion syndrome, hepatocerebral form |
c.101C>G | p.Ser34Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Charcot-Marie-Tooth disease, axonal, type 2EE |
c.103C>T | p.Gln35Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Charcot-Marie-Tooth disease, axonal, type 2EE |
c.354dup | p.Asn119fs | Pathogenic/Likely pathogenic | ★★☆☆ | Charcot-Marie-Tooth disease, axonal, type 2EE |
c.391del | p.Ile132fs | Pathogenic/Likely pathogenic | ★★☆☆ | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) |
c.405C>A | p.Tyr135Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) |
c.405C>G | p.Tyr135Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Mitochondrial DNA depletion syndrome, hepatocerebral form |
c.461+1G>C | - | Pathogenic | ★★☆☆ | Charcot-Marie-Tooth disease, axonal, type 2EE |
c.70+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Mitochondrial DNA depletion syndrome, hepatocerebral form |
c.70+5G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Mitochondrial DNA depletion syndrome |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the MPV17 gene are primarily associated with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome. This severe autosomal recessive condition is characterised by significant liver disease and neurological problems, typically presenting in infancy. Another condition, Charcot-Marie-Tooth disease, has also been linked to MPV17 gene variants, although MPV17-related forms are less common.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic MPV17 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
In the UK, the MPV17 gene is included on several NHS Genomic Medicine Service national test panels. It is reviewed in the context of various conditions, including Cholestasis, DDG2P, Hereditary neuropathy, Hereditary neuropathy or pain disorder, Likely inborn error of metabolism, Mitochondrial disorders, Mitochondrial DNA maintenance disorder, Mitochondrial liver disease, Neonatal cholestasis, Paediatric pseudo-obstruction syndrome, Possible mitochondrial disorder, nuclear genes, and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the MPV17 gene?
The MPV17 gene encodes a protein located in the inner membrane of mitochondria, where it is thought to play a crucial role in maintaining mitochondrial DNA (mtDNA), which is essential for cellular energy production.
What kind of conditions are associated with MPV17 gene variants?
Pathogenic variants in the MPV17 gene are primarily linked to MPV17-related hepatocerebral mitochondrial DNA depletion syndrome, a severe condition affecting the liver and brain that typically appears in infancy.
How is MPV17-related hepatocerebral mitochondrial DNA depletion syndrome inherited?
This condition follows an autosomal recessive inheritance pattern, meaning an individual must inherit two pathogenic variants (one from each parent) in the MPV17 gene to develop the syndrome.
References
- El-Hattab AW, Li FY, Schmitt E. MPV17-associated hepatocerebral mitochondrial DNA depletion syndrome: new patients and novel mutations. Molecular genetics and metabolism. 2010. PMID: 20074988
- Spinazzola A, Santer R, Akman OH. Hepatocerebral form of mitochondrial DNA depletion syndrome: novel MPV17 mutations. Archives of neurology. 2008. PMID: 18695062
- Wong LJ, Brunetti-Pierri N, Zhang Q. Mutations in the MPV17 gene are responsible for rapidly progressive liver failure in infancy. Hepatology (Baltimore, Md.). 2007. PMID: 17694548
- Spinazzola A, Viscomi C, Fernandez-Vizarra E. MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nature genetics. 2006. PMID: 16582910
- Karadimas CL, Vu TH, Holve SA. Navajo neurohepatopathy is caused by a mutation in the MPV17 gene. American journal of human genetics. 2006. PMID: 16909392