Reviewed June 2009
What is the official name of the OPA1 gene?
The official name of this gene is “optic atrophy 1 (autosomal dominant).”
OPA1 is the gene's official symbol. The OPA1 gene is also known by other names, listed below.
What is the normal function of the OPA1 gene?
The OPA1 gene provides instructions for making a protein that helps determine the shape and structure (morphology) of mitochondria, the energy-producing centers within cells. The OPA1 protein is made in many types of cells and tissues, including the brain, the light-sensitive tissue at the back of the eye (the retina), muscles used for movement (skeletal muscles), the liver, and the heart. Within cells, this protein is found in the inner membrane of mitochondria. Mitochondria are dynamic structures that undergo changes in morphology through processes called fission (splitting into smaller pieces) and fusion (combining pieces). These changes in morphology are necessary for mitochondria to function properly. The OPA1 protein helps to regulate the morphology of mitochondria by playing a key role in the fusion process.
The OPA1 protein is also involved in a process called oxidative phosphorylation, from which cells derive much of their energy. Additionally, the OPA1 protein plays a role in the maintenance of the small amount of DNA within mitochondria, called mitochondrial DNA (mtDNA), and in the self-destruction of cells (apoptosis).
How are changes in the OPA1 gene related to health conditions?
- optic atrophy type 1 - caused by mutations in the OPA1 gene
More than 200 mutations in the OPA1 gene have been found to cause optic atrophy type 1. Most of these mutations create a premature stop signal in the instructions for making the OPA1 protein. As a result, an abnormally small protein is produced, which is likely to be unstable and broken down quickly. The most common mutation that causes optic atrophy type 1 deletes four DNA building blocks (nucleotides) in the OPA1 gene (written as 2708delTTAG).
OPA1 gene mutations lead to overall dysfunction of the mitochondria and the breakdown of structures that transmit visual information from the eyes to the brain. Affected individuals first experience a progressive loss of nerve cells that line the retina, called retinal ganglion cells. The loss of these cells is followed by the degeneration (atrophy) of the optic nerve. The optic nerve is partly made up of specialized extensions of retinal ganglion cells called axons; when the retinal ganglion cells die, the optic nerve cannot transmit visual information to the brain normally. It is unclear why the OPA1 gene mutations that cause optic atrophy type 1 only affect the eyes. Retinal ganglion cells have many mitochondria and especially high energy requirements, which researchers believe may make them particularly vulnerable to mitochondrial dysfunction and decreases in energy production.
- other disorders - caused by mutations in the OPA1 gene
Some mutations in the OPA1 gene cause the features of optic atrophy type 1 but also affect other body systems. One condition, called optic atrophy type 1 and deafness, causes vision loss and hearing loss. OPA1 mutations also cause a second, more severe condition known as autosomal dominant optic atrophy (ADOA)-plus syndrome. This condition involves vision loss, weakness in the muscles that control eye movement (progressive external ophthalmoplegia), difficulty with balance and coordination (ataxia), hearing loss, disturbances in the nerves used for muscle movement and sensation (motor and sensory neuropathy), and muscle weakness (myopathy).
In most cases, these two conditions are caused by the same mutation. This mutation replaces the protein building block (amino acid) arginine with the amino acid histidine at position 445 in the OPA1 protein (written as Arg445His or R445H). It is unclear why the R445H mutation causes other features in addition to vision loss in affected individuals.
Where is the OPA1 gene located?
Cytogenetic Location: 3q29
Molecular Location on chromosome 3: base pairs 193,593,143 to 193,697,810
The OPA1 gene is located on the long (q) arm of chromosome 3 at position 29.
More precisely, the OPA1 gene is located from base pair 193,593,143 to base pair 193,697,810 on chromosome 3.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about OPA1?
You and your healthcare professional may find the following resources about OPA1 helpful.
Educational resources - Information pages
- Neuroscience (second edition, 2001): Central Projections of Retinal Ganglion Cells (http://www.ncbi.nlm.nih.gov/books/NBK11145/)
- Neuroscience (second edition, 2001): Central Projections of Retinal Ganglion Cells (picture) (http://www.ncbi.nlm.nih.gov/books/NBK11145/figure/A825/)
- Webvision--The Organization of the Retina and Visual System: Retinal Ganglion Cells (http://www.ncbi.nlm.nih.gov/books/NBK11558/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1248/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for OPA1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=4976%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=(OPA1%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- OPA1 GENE (http://omim.org/entry/605290)
- OPTIC ATROPHY WITH OR WITHOUT DEAFNESS, OPHTHALMOPLEGIA, MYOPATHY, ATAXIA, AND NEUROPATHY (http://omim.org/entry/125250)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_OPA1.html)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=4976)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=8140)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4976)
What other names do people use for the OPA1 gene or gene products?
- mitochondrial dynamin-like GTPase
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 OPA1?
amino acid ;
autosomal dominant ;
optic atrophy ;
optic nerve ;
oxidative phosphorylation ;
retinal ganglion ;
retinal ganglion cells ;
sensory neuropathy ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Amati-Bonneau P, Guichet A, Olichon A, Chevrollier A, Viala F, Miot S, Ayuso C, Odent S, Arrouet C, Verny C, Calmels MN, Simard G, Belenguer P, Wang J, Puel JL, Hamel C, Malthièry Y, Bonneau D, Lenaers G, Reynier P. OPA1 R445H mutation in optic atrophy associated with sensorineural deafness. Ann Neurol. 2005 Dec;58(6):958-63. (http://www.ncbi.nlm.nih.gov/pubmed/16240368?dopt=Abstract)
- Amati-Bonneau P, Milea D, Bonneau D, Chevrollier A, Ferré M, Guillet V, Gueguen N, Loiseau D, de Crescenzo MA, Verny C, Procaccio V, Lenaers G, Reynier P. OPA1-associated disorders: phenotypes and pathophysiology. Int J Biochem Cell Biol. 2009 Oct;41(10):1855-65. doi: 10.1016/j.biocel.2009.04.012. Epub 2009 Apr 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19389487?dopt=Abstract)
- Amati-Bonneau P, Valentino ML, Reynier P, Gallardo ME, Bornstein B, Boissière A, Campos Y, Rivera H, de la Aleja JG, Carroccia R, Iommarini L, Labauge P, Figarella-Branger D, Marcorelles P, Furby A, Beauvais K, Letournel F, Liguori R, La Morgia C, Montagna P, Liguori M, Zanna C, Rugolo M, Cossarizza A, Wissinger B, Verny C, Schwarzenbacher R, Martín MA, Arenas J, Ayuso C, Garesse R, Lenaers G, Bonneau D, Carelli V. OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes. Brain. 2008 Feb;131(Pt 2):338-51. Epub 2007 Dec 24. (http://www.ncbi.nlm.nih.gov/pubmed/18158317?dopt=Abstract)
- Chen H, Chan DC. Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:R283-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16244327?dopt=Abstract)
- Davies V, Votruba M. Focus on molecules: the OPA1 protein. Exp Eye Res. 2006 Nov;83(5):1003-4. Epub 2006 Mar 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16563384?dopt=Abstract)
- Ferré M, Bonneau D, Milea D, Chevrollier A, Verny C, Dollfus H, Ayuso C, Defoort S, Vignal C, Zanlonghi X, Charlin JF, Kaplan J, Odent S, Hamel CP, Procaccio V, Reynier P, Amati-Bonneau P. Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations. Hum Mutat. 2009 Jul;30(7):E692-705. doi: 10.1002/humu.21025. (http://www.ncbi.nlm.nih.gov/pubmed/19319978?dopt=Abstract)
- Fuhrmann N, Alavi MV, Bitoun P, Woernle S, Auburger G, Leo-Kottler B, Yu-Wai-Man P, Chinnery P, Wissinger B. Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy. J Med Genet. 2009 Feb;46(2):136-44. doi: 10.1136/jmg.2008.062570. (http://www.ncbi.nlm.nih.gov/pubmed/19181907?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4976)
- Olichon A, Guillou E, Delettre C, Landes T, Arnauné-Pelloquin L, Emorine LJ, Mils V, Daloyau M, Hamel C, Amati-Bonneau P, Bonneau D, Reynier P, Lenaers G, Belenguer P. Mitochondrial dynamics and disease, OPA1. Biochim Biophys Acta. 2006 May-Jun;1763(5-6):500-9. Epub 2006 Apr 20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16737747?dopt=Abstract)
- OMIM: OPA1 GENE (http://omim.org/entry/605290)
- Schimpf S, Fuhrmann N, Schaich S, Wissinger B. Comprehensive cDNA study and quantitative transcript analysis of mutant OPA1 transcripts containing premature termination codons. Hum Mutat. 2008 Jan;29(1):106-12. (http://www.ncbi.nlm.nih.gov/pubmed/17722006?dopt=Abstract)
- Zanna C, Ghelli A, Porcelli AM, Karbowski M, Youle RJ, Schimpf S, Wissinger B, Pinti M, Cossarizza A, Vidoni S, Valentino ML, Rugolo M, Carelli V. OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain. 2008 Feb;131(Pt 2):352-67. doi: 10.1093/brain/awm335. (http://www.ncbi.nlm.nih.gov/pubmed/18222991?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.