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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed May 2014

What is the official name of the MT-TL1 gene?

The official name of this gene is “mitochondrially encoded tRNA leucine 1 (UUA/G).”

MT-TL1 is the gene's official symbol. The MT-TL1 gene is also known by other names, listed below.

What is the normal function of the MT-TL1 gene?

The MT-TL1 gene provides instructions for making a molecule called a transfer RNA (tRNA), which is a chemical cousin of DNA. Transfer RNAs help assemble protein building blocks (amino acids) into functioning proteins. The MT-TL1 gene provides instructions for making a specific form of tRNA that is designated as tRNALeu(UUR). During protein assembly, this molecule attaches to the amino acid leucine (Leu) and inserts it into the appropriate locations in the growing protein.

The tRNALeu(UUR) molecule is present in cellular structures called mitochondria. These structures convert energy from food into a form that cells can use. Within mitochondria, tRNALeu(UUR) is involved in the assembly of proteins that carry out a series of chemical steps called oxidative phosphorylation. This process uses oxygen, simple sugars, and fatty acids to create adenosine triphosphate (ATP), the cell's main energy source.

In certain cells in the pancreas, called beta cells, mitochondria also play a role in controlling the amount of sugar (glucose) in the bloodstream. In response to high glucose levels, mitochondria help trigger the release of a hormone called insulin. Insulin regulates blood sugar levels by controlling how much glucose is passed from the blood into cells to be converted into energy.

Does the MT-TL1 gene share characteristics with other genes?

The MT-TL1 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? ( in the Handbook.

How are changes in the MT-TL1 gene related to health conditions?

maternally inherited diabetes and deafness - caused by mutations in the MT-TL1 gene

At least one mutation in the MT-TL1 gene causes maternally inherited diabetes and deafness (MIDD). People with this condition have diabetes and sometimes hearing loss, particularly of high tones. Less commonly, affected individuals have problems with their eyes, muscles, heart, or kidneys. The MT-TL1 gene mutation is the most common mutation in MIDD, involved in 85 percent of cases. It changes a single DNA building block (nucleotide) in the MT-TL1 gene; the nucleotide adenine is replaced by the nucleotide guanine at position 3243 in the gene (written as A3243G).

The A3243G mutation reduces the ability of tRNALeu(UUR) to add leucine to proteins that are being assembled, which slows protein production. Researchers believe that the A3243G mutation impairs the ability of mitochondria to help trigger insulin release. In people with MIDD, diabetes results when the beta cells do not produce enough insulin to regulate blood sugar effectively. Researchers have not determined how the A3243G mutation leads to hearing loss or the other features of MIDD.

mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes - caused by mutations in the MT-TL1 gene

Several mutations in the MT-TL1 gene have been identified in people with a condition called mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). 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. Most of these mutations change single nucleotides in the gene. The A3243G mutation (described above) is the most common mutation in MELAS. It is responsible for about 80 percent of all MELAS cases. This mutation impairs the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mtDNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain.

myoclonic epilepsy with ragged-red fibers - caused by mutations in the MT-TL1 gene

Mutations in the MT-TL1 gene have been found in a few people with features of myoclonic epilepsy with ragged-red fibers (MERRF). These individuals also have some features of MELAS (described above). This combination of signs and symptoms is called MERRF/MELAS overlap syndrome. The features of this syndrome include muscle twitches (myoclonus), muscle weakness (myopathy), difficulty coordinating movement (ataxia), hearing loss, seizures, and diabetes.

Mutations that cause MERRF/MELAS overlap syndrome each change single nucleotides in the MT-TL1 gene. Researchers have not determined how these genetic changes cause the signs and symptoms of MERRF/MELAS overlap syndrome.

progressive external ophthalmoplegia - caused by mutations in the MT-TL1 gene

Mutations in the MT-TL1 gene are responsible for some cases of an eye condition called progressive external ophthalmoplegia. This disorder weakens the muscles that control eye movement and causes drooping eyelids (ptosis).

Some cases of progressive external ophthalmoplegia result from the A3243G mutation, which is the same genetic change that typically causes MELAS and MIDD (described above). It is unclear how the same MT-TL1 gene mutation can result in different conditions. Researchers have not determined how changes in mtDNA lead to the specific signs and symptoms of progressive external ophthalmoplegia, although the features of the condition may be related to impaired oxidative phosphorylation. It has been suggested that eye muscles are commonly affected by mitochondrial defects because they are especially dependent on oxidative phosphorylation for energy.

other disorders - associated with the MT-TL1 gene

About 20 mutations in the MT-TL1 gene have been reported, most of which change single nucleotides in the gene. These mutations are associated with a variety of signs and symptoms chiefly affecting the muscles and nervous system. People with MT-TL1 mutations often have muscle weakness, pain, and extreme fatigue, particularly during exercise (exercise intolerance). In some cases, the heart muscle is also weakened, which is known as cardiomyopathy. This abnormality prevents the heart from pumping normally.

A few children with changes in the MT-TL1 gene have experienced delayed development, psychiatric problems, or developmental disorders that affect communication and social interaction (autistic spectrum disorders). MT-TL1 mutations also have been identified in a small number of cases of sudden infant death syndrome (SIDS), which is a major cause of death in children younger than 1 year.

Where is the MT-TL1 gene located?

The MT-TL1 gene is located in mitochondrial DNA.

Molecular Location in mitochondrial DNA: base pairs 3,230 to 3,304

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (

Overview of gene located on mitochondrial DNA Close-up of gene located on mitochondrial DNA

Where can I find additional information about MT-TL1?

You and your healthcare professional may find the following resources about MT-TL1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the MT-TL1 gene or gene products?

  • MTTL1
  • tRNA leucine 1 (UUA/G)

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding MT-TL1?

acidosis ; acids ; adenine ; adenosine triphosphate ; amino acid ; ataxia ; ATP ; cardiomyopathy ; cell ; diabetes ; DNA ; epilepsy ; fatty acids ; gene ; glucose ; guanine ; hormone ; inherited ; insulin ; lactic acidosis ; Leu ; leucine ; mitochondria ; molecule ; mutation ; myoclonus ; nervous system ; nucleotide ; ophthalmoplegia ; oxidative phosphorylation ; oxygen ; pancreas ; phosphorylation ; protein ; ptosis ; RNA ; spectrum ; syndrome ; transfer RNA ; tRNA

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Betts J, Jaros E, Perry RH, Schaefer AM, Taylor RW, Abdel-All Z, Lightowlers RN, Turnbull DM. Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement. Neuropathol Appl Neurobiol. 2006 Aug;32(4):359-73. (
  • Brackmann F, Abicht A, Ahting U, Schröder R, Trollmann R. Classical MERRF phenotype associated with mitochondrial tRNA(Leu) (m.3243A>G) mutation. Eur J Pediatr. 2012 May;171(5):859-62. doi: 10.1007/s00431-011-1662-8. Epub 2012 Jan 25. (
  • Chinnery PF, Howell N, Lightowlers RN, Turnbull DM. Molecular pathology of MELAS and MERRF. The relationship between mutation load and clinical phenotypes. Brain. 1997 Oct;120 ( Pt 10):1713-21. (
  • Choi BO, Hwang JH, Cho EM, Jeong EH, Hyun YS, Jeon HJ, Seong KM, Cho NS, Chung KW. Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases. Exp Mol Med. 2010 Jun 30;42(6):446-55. (
  • Kirino Y, Goto Y, Campos Y, Arenas J, Suzuki T. Specific correlation between the wobble modification deficiency in mutant tRNAs and the clinical features of a human mitochondrial disease. Proc Natl Acad Sci U S A. 2005 May 17;102(20):7127-32. Epub 2005 May 3. (
  • Liu K, Zhao H, Ji K, Yan C. MERRF/MELAS overlap syndrome due to the m.3291T>C mutation. Metab Brain Dis. 2014 Mar;29(1):139-44. doi: 10.1007/s11011-013-9464-5. Epub 2013 Dec 12. (
  • Maassen JA, Jahangir Tafrechi RS, Janssen GM, Raap AK, Lemkes HH, 't Hart LM. New insights in the molecular pathogenesis of the maternally inherited diabetes and deafness syndrome. Endocrinol Metab Clin North Am. 2006 Jun;35(2):385-96, x-xi. Review. (
  • Moraes CT, Ciacci F, Bonilla E, Jansen C, Hirano M, Rao N, Lovelace RE, Rowland LP, Schon EA, DiMauro S. Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot? J Clin Invest. 1993 Dec;92(6):2906-15. (
  • Murphy R, Turnbull DM, Walker M, Hattersley AT. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet Med. 2008 Apr;25(4):383-99. doi: 10.1111/j.1464-5491.2008.02359.x. Epub 2008 Feb 18. Review. (
  • NCBI Gene (
  • Opdal SH, Rognum TO, Torgersen H, Vege A. Mitochondrial DNA point mutations detected in four cases of sudden infant death syndrome. Acta Paediatr. 1999 Sep;88(9):957-60. (
  • Palecek T, Tesarova M, Kuchynka P, Dytrych V, Elleder M, Hulkova H, Hansikova H, Honzik T, Zeman J, Linhart A. Hypertrophic cardiomyopathy due to the mitochondrial DNA mutation m.3303C>T diagnosed in an adult male. Int Heart J. 2012;53(6):383-7. (
  • Yarham JW, Blakely EL, Alston CL, Roberts ME, Ealing J, Pal P, Turnbull DM, McFarland R, Taylor RW. The m.3291T>C mt-tRNA(Leu(UUR)) mutation is definitely pathogenic and causes multisystem mitochondrial disease. J Neurol Sci. 2013 Feb 15;325(1-2):165-9. doi: 10.1016/j.jns.2012.12.003. Epub 2012 Dec 27. (
  • Yu Wai Man CY, Chinnery PF, Griffiths PG. Extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders. Neuromuscul Disord. 2005 Jan;15(1):17-23. Epub 2004 Nov 26. Review. (


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 healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: May 2014
Published: February 8, 2016