Reviewed November 2006
What is the official name of the MT-ND5 gene?
The official name of this gene is “mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 5.”
MT-ND5 is the gene's official symbol. The MT-ND5 gene is also known by other names, listed below.
What is the normal function of the MT-ND5 gene?
The MT-ND5 gene provides instructions for making a protein called NADH dehydrogenase 5. This protein is part of a large enzyme complex known as complex I, which is active in mitochondria. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. These cellular structures produce energy through a process called oxidative phosphorylation, which uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source.
Complex I is one of several enzyme complexes necessary for oxidative phosphorylation. Within mitochondria, these complexes are embedded in a tightly folded, specialized membrane called the inner mitochondrial membrane. During oxidative phosphorylation, mitochondrial enzyme complexes carry out chemical reactions that drive the production of ATP. Specifically, they create an unequal electrical charge on either side of the inner mitochondrial membrane through a step-by-step transfer of negatively charged particles called electrons. This difference in electrical charge provides the energy for ATP production.
Complex I is responsible for the first step in the electron transport process, the transfer of electrons from a molecule called NADH to another molecule called ubiquinone. Electrons are then passed from ubiquinone through several other enzyme complexes to provide energy for the generation of ATP.
How are changes in the MT-ND5 gene related to health conditions?
- mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - caused by mutations in the MT-ND5 gene
Mutations in the MT-ND5 gene are responsible for a small percentage of all cases of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These mutations alter single DNA building blocks (nucleotides) in the gene. A particular mutation has been identified in at least five people with the characteristic features of MELAS; this mutation replaces the nucleotide guanine with the nucleotide adenine at gene position 13513 (written as G13513A). Most of the MT-ND5 mutations that cause MELAS have been shown to reduce the activity of complex I, which disrupts energy production within mitochondria. Although these abnormalities have the greatest impact on tissues that require a lot of energy (such as the brain and muscles), researchers have not determined how changes in the MT-ND5 gene lead to the specific signs and symptoms of MELAS.
Mutations in the MT-ND5 gene also have been identified in patients with the major features of MELAS in combination with other mitochondrial diseases. For example, researchers have found MT-ND5 mutations in several individuals with the signs of MELAS and some features of Leigh syndrome, a progressive brain disorder that typically appears in infancy or early childhood. In other cases, people with MELAS and a change in the MT-ND5 gene have developed sudden, progressive vision loss characteristic of an eye disease called Leber hereditary optic neuropathy. A few individuals have been reported with signs and symptoms of all three of these mitochondrial conditions—MELAS, Leigh syndrome, and Leber hereditary optic neuropathy.
It is unclear why changes in the MT-ND5 gene can cause such a large variety of signs and symptoms. Even within a single family, affected individuals may have different health problems caused by the same genetic change.
- other disorders - caused by mutations in the MT-ND5 gene
Mutations in the MT-ND5 gene have been identified in at least 10 people with Leigh syndrome. Children with this condition may experience vomiting, seizures, delayed development, muscle weakness, and problems with movement. Heart disease, kidney problems, and difficulty breathing can also occur in people with this disorder. A few affected children with MT-ND5 mutations have had additional features that are not typical of Leigh syndrome, including slow growth before birth (intrauterine growth retardation) and distinctive facial features.
The MT-ND5 mutations responsible for Leigh syndrome change single nucleotides in the gene. These genetic changes disrupt the activity of complex I, impairing the ability of mitochondria to produce energy. It is not known, however, how mutations in the MT-ND5 gene are related to the specific features of Leigh syndrome.
Where is the MT-ND5 gene located?
The MT-ND5 gene is located in mitochondrial DNA.
Molecular Location in mitochondrial DNA: base pairs 12,337 to 14,148
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/4540))
Where can I find additional information about MT-ND5?
You and your healthcare professional may find the following resources about MT-ND5 helpful.
Educational resources - Information pages
- Basic Neurochemistry (sixth edition, 1999): Diseases of Mitochondrial Metabolism (http://www.ncbi.nlm.nih.gov/books/NBK27914/)
- Biochemistry (fifth edition, 2002): Oxidative Phosphorylation (http://www.ncbi.nlm.nih.gov/books/NBK21208/)
- Indiana University School of Medicine: Complexes of the electron transport chain (http://themedicalbiochemistrypage.org/oxidative-phosphorylation.html)
- Mayo Clinic Mitochondrial Disease Biobank (http://www.mayo.edu/research/centers-programs/mitochondrial-disease-biobank/overview)
- The Neuromuscular Disease Center at Washington University: Complex I (http://neuromuscular.wustl.edu/pathol/diagrams/mito.htm)
Gene Reviews - Clinical summary
- Gene Review: MELAS (http://www.ncbi.nlm.nih.gov/books/NBK1233)
- Gene Review: Mitochondrial Disorders Overview (http://www.ncbi.nlm.nih.gov/books/NBK1224)
- Gene Review: Mitochondrial DNA-Associated Leigh Syndrome and NARP (http://www.ncbi.nlm.nih.gov/books/NBK1173)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for MT-ND5 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4540%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28MT-ND5%5BTIAB%5D%29%20OR%20%28mitochondrially%20encoded%20NADH%20dehydrogenase%205%5BTIAB%5D%29%29%20OR%20%28%28MTND5%5BTIAB%5D%29%20OR%20%28NADH%20dehydrogenase%20subunit%205%5BTIAB%5D%29%20OR%20%28NADH5%5BTIAB%5D%29%20OR%20%28ND5%5BTIAB%5D%29%20OR%20%28NADH-ubiquinone%20oxidoreductase%20chain%205%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201440%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- COMPLEX I, SUBUNIT ND5 (http://omim.org/entry/516005)
- LEIGH SYNDROME (http://omim.org/entry/256000)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_ND5.html)
- HGNC Gene Family: NADH:ubiquinone oxidoreductase core subunits (http://www.genenames.org/cgi-bin/genefamilies/set/1149)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=7461)
- Mitomap: Coding and Control Region Mutations (http://www.mitomap.org/MITOMAP/MutationsCodingControl)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4540)
What other names do people use for the MT-ND5 gene or gene products?
- mitochondrially encoded NADH dehydrogenase 5
- NADH dehydrogenase subunit 5
- NADH-ubiquinone oxidoreductase chain 5
- NADH-ubiquinone oxidoreductase, subunit ND5
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding MT-ND5?
adenosine triphosphate ;
charged particles ;
intrauterine growth retardation ;
lactic acidosis ;
oxidative phosphorylation ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Chol M, Lebon S, Bénit P, Chretien D, de Lonlay P, Goldenberg A, Odent S, Hertz-Pannier L, Vincent-Delorme C, Cormier-Daire V, Rustin P, Rötig A, Munnich A. The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency. J Med Genet. 2003 Mar;40(3):188-91. (http://www.ncbi.nlm.nih.gov/pubmed/12624137?dopt=Abstract)
- Corona P, Antozzi C, Carrara F, D'Incerti L, Lamantea E, Tiranti V, Zeviani M. A novel mtDNA mutation in the ND5 subunit of complex I in two MELAS patients. Ann Neurol. 2001 Jan;49(1):106-10. (http://www.ncbi.nlm.nih.gov/pubmed/11198278?dopt=Abstract)
- Crimi M, Galbiati S, Moroni I, Bordoni A, Perini MP, Lamantea E, Sciacco M, Zeviani M, Biunno I, Moggio M, Scarlato G, Comi GP. A missense mutation in the mitochondrial ND5 gene associated with a Leigh-MELAS overlap syndrome. Neurology. 2003 Jun 10;60(11):1857-61. (http://www.ncbi.nlm.nih.gov/pubmed/12796552?dopt=Abstract)
- Kirby DM, Boneh A, Chow CW, Ohtake A, Ryan MT, Thyagarajan D, Thorburn DR. Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease. Ann Neurol. 2003 Oct;54(4):473-8. (http://www.ncbi.nlm.nih.gov/pubmed/14520659?dopt=Abstract)
- Liolitsa D, Rahman S, Benton S, Carr LJ, Hanna MG. Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations? Ann Neurol. 2003 Jan;53(1):128-32. (http://www.ncbi.nlm.nih.gov/pubmed/12509858?dopt=Abstract)
- Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM. Sequence variation in mitochondrial complex I genes: mutation or polymorphism? J Med Genet. 2006 Feb;43(2):175-9. Epub 2005 Jun 21. (http://www.ncbi.nlm.nih.gov/pubmed/15972314?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4540)
- Pulkes T, Eunson L, Patterson V, Siddiqui A, Wood NW, Nelson IP, Morgan-Hughes JA, Hanna MG. The mitochondrial DNA G13513A transition in ND5 is associated with a LHON/MELAS overlap syndrome and may be a frequent cause of MELAS. Ann Neurol. 1999 Dec;46(6):916-9. Erratum in: Ann Neurol 2000 Jun;47(6):841. (http://www.ncbi.nlm.nih.gov/pubmed/10589546?dopt=Abstract)
- Santorelli FM, Tanji K, Kulikova R, Shanske S, Vilarinho L, Hays AP, DiMauro S. Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS. Biochem Biophys Res Commun. 1997 Sep 18;238(2):326-8. (http://www.ncbi.nlm.nih.gov/pubmed/9299505?dopt=Abstract)
- Sudo A, Honzawa S, Nonaka I, Goto Y. Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan. J Hum Genet. 2004;49(2):92-6. Epub 2004 Jan 17. (http://www.ncbi.nlm.nih.gov/pubmed/14730434?dopt=Abstract)
- Valentino ML, Barboni P, Rengo C, Achilli A, Torroni A, Lodi R, Tonon C, Barbiroli B, Fortuna F, Montagna P, Baruzzi A, Carelli V. The 13042G --> A/ND5 mutation in mtDNA is pathogenic and can be associated also with a prevalent ocular phenotype. J Med Genet. 2006 Jul;43(7):e38. (http://www.ncbi.nlm.nih.gov/pubmed/16816025?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.