Reviewed May 2014
What is the official name of the MT-TH gene?
The official name of this gene is “mitochondrially encoded tRNA histidine.”
MT-TH is the gene's official symbol. The MT-TH gene is also known by other names, listed below.
What is the normal function of the MT-TH gene?
The MT-TH gene provides instructions for making a particular type of RNA, a molecule that is a chemical cousin of DNA. This type of RNA, called transfer RNA (tRNA), helps assemble protein building blocks known as amino acids into full-length, functioning proteins. The MT-TH gene provides instructions for a specific form of tRNA that is designated as tRNAHis. During protein assembly, this molecule attaches to a particular amino acid, histidine (His), and inserts it into the appropriate locations in the growing protein.
The tRNAHis molecule is present in cellular structures called mitochondria. These structures convert energy from food into a form that cells can use. Through a process called oxidative phosphorylation, mitochondria use oxygen, simple sugars, and fatty acids to create adenosine triphosphate (ATP), the cell's main energy source. The tRNAHis molecule is involved in the assembly of proteins that carry out oxidative phosphorylation.
Does the MT-TH gene share characteristics with other genes?
The MT-TH gene belongs to a family of genes called TRNA (transfer RNAs).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the MT-TH gene related to health conditions?
- mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - caused by mutations in the MT-TH gene
A small number of people with the features of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) have a mutation in the MT-TH gene. This condition is characterized by recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes including a loss of consciousness, seizures, and other problems affecting the nervous system. Some people with an MT-TH gene mutation also have features of another mitochondrial disorder called myoclonic epilepsy with ragged-red fibers (MERRF); these additional features can include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known as ragged-red fibers. This combination of signs and symptoms is called MERRF/MELAS overlap syndrome.
MT-TH gene mutations that cause MELAS and MERRF/MELAS overlap syndrome change single DNA building blocks (nucleotides) in the gene. Researchers have not determined how these genetic changes alter energy production in mitochondria or cause the varied signs and symptoms of MELAS or MERRF/MELAS overlap syndrome.
- myoclonic epilepsy with ragged-red fibers - caused by mutations in the MT-TH gene
As mentioned above, a few individuals with a mutation in the MT-TH gene have features of both myoclonic epilepsy with ragged-red fibers (MERRF) and MELAS. The mutation involved in this overlap syndrome replaces the nucleotide guanine with the nucleotide adenine at gene position 12147 (written as G12147A). It remains unknown why this mutation causes the overlapping features of MERRF and MELAS.
- other disorders - associated with the MT-TH gene
Another mutation in the MT-TH gene may increase the risk of developing a heart condition called cardiomyopathy. People with cardiomyopathy have a weakened heart muscle that is unable to pump blood effectively. A particular change in the MT-TH gene has been identified in several adults with cardiomyopathy, but without other common signs of mitochondrial disease such as neurological abnormalities. This mutation replaces the nucleotide guanine with the nucleotide adenine at gene position 12192 (written as G12192A). It is unclear why this alteration in mitochondrial DNA may increase a person's risk of developing heart problems without affecting other parts of the body.
Where is the MT-TH gene located?
The MT-TH gene is located in mitochondrial DNA.
Molecular Location in mitochondrial DNA: base pairs 12,138 to 12,206
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/4564))
Where can I find additional information about MT-TH?
You and your healthcare professional may find the following resources about MT-TH helpful.
Educational resources - Information pages
- Basic Neurochemistry (sixth edition, 1999): Diseases of Mitochondrial Metabolism (http://www.ncbi.nlm.nih.gov/books/NBK27914/)
- Madame Curie Bioscience Database: Mitochondrial Translation System (http://www.ncbi.nlm.nih.gov/books/NBK6292/)
- Mayo Clinic Mitochondrial Disease Biobank (http://www.mayo.edu/research/centers-programs/mitochondrial-disease-biobank/overview)
- Neuromuscular Disease Center, Washington University: MELAS (http://neuromuscular.wustl.edu/mitosyn.html)
- Neuromuscular Disease Center, Washington University: MERRF (http://neuromuscular.wustl.edu/mitosyn.html)
- The Cell: A Molecular Approach (second edition, 2000): The Genetic System of Mitochondria (http://www.ncbi.nlm.nih.gov/books/NBK9896/)
Gene Reviews - Clinical summary
- Gene Review: MELAS (http://www.ncbi.nlm.nih.gov/books/NBK1233)
- Gene Review: MERRF (http://www.ncbi.nlm.nih.gov/books/NBK1520)
- Gene Review: Mitochondrial Disorders Overview (http://www.ncbi.nlm.nih.gov/books/NBK1224)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for MT-TH (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4564%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%28MTTH%5BTIAB%5D%29%20OR%20%28tRNA%20histidine%5BTIAB%5D%29%29%20OR%20%28%28G12147A%5BTIAB%5D%29%20OR%20%28G12192A%5BTIAB%5D%29%29%20OR%20%28tRNA%28His%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/590040)
Research Resources - Tools for researchers
- HGNC Gene Family: Mitochondrially encoded tRNAs (http://www.genenames.org/cgi-bin/genefamilies/set/843)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=7487)
- Mitomap: rRNA/tRNA mutations (http://www.mitomap.org/MITOMAP/MutationsRNA)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4564)
What other names do people use for the MT-TH gene or gene products?
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-TH?
adenosine triphosphate ;
amino acid ;
fatty acids ;
lactic acidosis ;
muscle cells ;
nervous system ;
oxidative phosphorylation ;
transfer RNA ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Blakely EL, Yarham JW, Alston CL, Craig K, Poulton J, Brierley C, Park SM, Dean A, Xuereb JH, Anderson KN, Compston A, Allen C, Sharif S, Enevoldson P, Wilson M, Hammans SR, Turnbull DM, McFarland R, Taylor RW. Pathogenic mitochondrial tRNA point mutations: nine novel mutations affirm their importance as a cause of mitochondrial disease. Hum Mutat. 2013 Sep;34(9):1260-8. doi: 10.1002/humu.22358. (http://www.ncbi.nlm.nih.gov/pubmed/23696415?dopt=Abstract)
- Calvaruso MA, Willemsen MA, Rodenburg RJ, van den Brand M, Smeitink JA, Nijtmans L. New mitochondrial tRNA HIS mutation in a family with lactic acidosis and stroke-like episodes (MELAS). Mitochondrion. 2011 Sep;11(5):778-82. doi: 10.1016/j.mito.2011.06.004. Epub 2011 Jun 17. (http://www.ncbi.nlm.nih.gov/pubmed/21704194?dopt=Abstract)
- Finsterer J, Harbo HF, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, De Jonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen CM, Zeviani M, Burgunder JM, Gasser T; European Federation of Neurological Sciences. EFNS guidelines on the molecular diagnosis of mitochondrial disorders. Eur J Neurol. 2009 Dec;16(12):1255-64. (http://www.ncbi.nlm.nih.gov/pubmed/19950421?dopt=Abstract)
- Melone MA, Tessa A, Petrini S, Lus G, Sampaolo S, di Fede G, Santorelli FM, Cotrufo R. Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF phenotype. Arch Neurol. 2004 Feb;61(2):269-72. (http://www.ncbi.nlm.nih.gov/pubmed/14967777?dopt=Abstract)
- Mimaki M, Ikota A, Sato A, Komaki H, Akanuma J, Nonaka I, Goto Y. A double mutation (G11778A and G12192A) in mitochondrial DNA associated with Leber's hereditary optic neuropathy and cardiomyopathy. J Hum Genet. 2003;48(1):47-50. (http://www.ncbi.nlm.nih.gov/pubmed/12560876?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4564)
- Shin WS, Tanaka M, Suzuki J, Hemmi C, Toyo-oka T. A novel homoplasmic mutation in mtDNA with a single evolutionary origin as a risk factor for cardiomyopathy. Am J Hum Genet. 2000 Dec;67(6):1617-20. Epub 2000 Oct 18. (http://www.ncbi.nlm.nih.gov/pubmed/11038324?dopt=Abstract)
- Taylor RW, Schaefer AM, McDonnell MT, Petty RK, Thomas AM, Blakely EL, Hayes CM, McFarland R, Turnbull DM. Catastrophic presentation of mitochondrial disease due to a mutation in the tRNA(His) gene. Neurology. 2004 Apr 27;62(8):1420-3. (http://www.ncbi.nlm.nih.gov/pubmed/15111688?dopt=Abstract)
- OMIM: TRANSFER RNA, MITOCHONDRIAL, HISTIDINE (http://omim.org/entry/590040)
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.