Reviewed December 2014
What is the official name of the C10orf2 gene?
The official name of this gene is “chromosome 10 open reading frame 2.”
C10orf2 is the gene's official symbol. The C10orf2 gene is also known by other names, listed below.
What is the normal function of the C10orf2 gene?
The C10orf2 gene provides instructions for making two very similar proteins called Twinkle and Twinky. These proteins are found in the mitochondria, which are structures in which a process called oxidative phosphorylation occurs to convert the energy from food into a form that cells can use.
Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. The Twinkle protein is involved in the production and maintenance of mtDNA. It functions as a mitochondrial DNA helicase, which means it binds to DNA and temporarily unwinds the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) mtDNA. The function of the Twinky protein is unknown.
How are changes in the C10orf2 gene related to health conditions?
- ataxia neuropathy spectrum - caused by mutations in the C10orf2 gene
Mutations in the C10orf2 gene have been found in a small number of people with ataxia neuropathy spectrum. This condition is characterized by problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). The conditions previously named mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO) are now included in ataxia neuropathy spectrum.
Mutations in the C10orf2 gene disrupt the function of Twinkle and lead to large deletions of mtDNA in the muscle tissue of affected individuals. However, it is unclear how mutations in the C10orf2 gene cause the signs and symptoms of ataxia neuropathy spectrum.
- infantile-onset spinocerebellar ataxia - caused by mutations in the C10orf2 gene
At least three mutations in the C10orf2 gene have been found to cause infantile-onset spinocerebellar ataxia (IOSCA). The most common mutation replaces the protein building block (amino acid) tyrosine with the amino acid cysteine at position 508 in the Twinkle protein, written as Tyr508Cys or Y508C. Most affected individuals have two copies of this gene mutation in each cell. At least two additional mutations have been reported that are unique to particular families. In these cases, affected individuals have one copy of the family-specific mutation and one copy of the Tyr508Cys mutation in each cell.
The C10orf2 gene mutations that cause IOSCA interfere with the function of the Twinkle protein and result in reduced quantities of mtDNA (mtDNA depletion). Impaired mitochondrial function, especially in the nervous system (which requires a large amount of energy), leads to neurological dysfunction and other problems associated with IOSCA.
- Perrault syndrome - caused by mutations in the C10orf2 gene
At least four C10orf2 gene mutations have been identified in families with Perrault syndrome, a condition characterized by hearing loss in affected males and females and abnormalities of the ovaries in affected females. The mutations involved in this condition change single amino acids in the Twinkle protein. Researchers predict that these mutations impair the helicase activity of the protein. However, it is unclear exactly how C10orf2 gene mutations lead to hearing problems and ovarian abnormalities in affected individuals.
- progressive external ophthalmoplegia - caused by mutations in the C10orf2 gene
More than 20 C10orf2 gene mutations have been identified in people with an eye condition called progressive external ophthalmoplegia. This disorder weakens the muscles that control eye movement and causes the eyelids to droop (ptosis). Researchers speculate that the mutated Twinkle protein has impaired helicase activity, which stalls the DNA replication process. Although the mechanism is unclear, replication stalling seems to result in large deletions of genetic material from mtDNA in muscle tissue. Researchers have not determined how deletions of 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 - caused by mutations in the C10orf2 gene
In a few families, C10orf2 gene mutations lead to mtDNA depletion syndrome, hepatocerebral form. People with this condition experience weak muscle tone (hypotonia), a decrease in liver function, developmental delay, seizures, and loss of sensation and weakness in the limbs (peripheral neuropathy).
Where is the C10orf2 gene located?
Cytogenetic Location: 10q24
Molecular Location on chromosome 10: base pairs 100,987,378 to 100,994,403
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/56652))
The C10orf2 gene is located on the long (q) arm of chromosome 10 at position 24.
More precisely, the C10orf2 gene is located from base pair 100,987,378 to base pair 100,994,403 on chromosome 10.
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 C10orf2?
You and your healthcare professional may find the following resources about C10orf2 helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth edition, 2002): How Cells Obtain Energy from Food (http://www.ncbi.nlm.nih.gov/books/NBK26882/)
- Molecular Cell Biology (fourth edition, 2000): Mitochondria are the Principal Sites of ATP Production in Aerobic Cells (http://www.ncbi.nlm.nih.gov/books/NBK21743/)
Gene Reviews - Clinical summary
- Gene Review: Infantile-Onset Spinocerebellar Ataxia (http://www.ncbi.nlm.nih.gov/books/NBK3795)
- Gene Review: Mitochondrial DNA Deletion Syndromes (http://www.ncbi.nlm.nih.gov/books/NBK1203)
- Gene Review: Perrault Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK242617)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for C10orf2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=56652%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%28C10orf2%5BTIAB%5D%29%20OR%20%28chromosome%2010%20open%20reading%20frame%202%5BTIAB%5D%29%29%20OR%20%28%28PEO%5BTIAB%5D%29%20OR%20%28PEO1%5BTIAB%5D%29%20OR%20%28IOSCA%5BTIAB%5D%29%20OR%20%28SANDO%5BTIAB%5D%29%20OR%20%28twinkle%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%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- CHROMOSOME 10 OPEN READING FRAME 2 (http://omim.org/entry/606075)
- MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE) (http://omim.org/entry/251880)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_C10orf2.html)
- HGNC Gene Family: DNA helicases (http://www.genenames.org/cgi-bin/genefamilies/set/1167)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=1160)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/56652)
What other names do people use for the C10orf2 gene or gene products?
- progressive external ophthalmoplegia 1 protein
- T7 gp4-like protein with intramitochondrial nucleoid localization
- T7-like mitochondrial DNA helicase
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 C10orf2?
amino acid ;
developmental delay ;
DNA replication ;
double helix ;
muscle tone ;
nervous system ;
open reading frame ;
oxidative phosphorylation ;
peripheral neuropathy ;
reading frame ;
You may find definitions for these and many other terms in the Genetics Home Reference
- OMIM: CHROMOSOME 10 OPEN READING FRAME 2 (http://omim.org/entry/606075)
- Goffart S, Cooper HM, Tyynismaa H, Wanrooij S, Suomalainen A, Spelbrink JN. Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling. Hum Mol Genet. 2009 Jan 15;18(2):328-40. doi: 10.1093/hmg/ddn359. Epub 2008 Oct 29. (http://www.ncbi.nlm.nih.gov/pubmed/18971204?dopt=Abstract)
- Hakonen AH, Goffart S, Marjavaara S, Paetau A, Cooper H, Mattila K, Lampinen M, Sajantila A, Lönnqvist T, Spelbrink JN, Suomalainen A. Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion. Hum Mol Genet. 2008 Dec 1;17(23):3822-35. doi: 10.1093/hmg/ddn280. Epub 2008 Sep 5. (http://www.ncbi.nlm.nih.gov/pubmed/18775955?dopt=Abstract)
- Hakonen AH, Isohanni P, Paetau A, Herva R, Suomalainen A, Lönnqvist T. Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain. 2007 Nov;130(Pt 11):3032-40. Epub 2007 Oct 5. (http://www.ncbi.nlm.nih.gov/pubmed/17921179?dopt=Abstract)
- Hudson G, Deschauer M, Busse K, Zierz S, Chinnery PF. Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism. Neurology. 2005 Jan 25;64(2):371-3. (http://www.ncbi.nlm.nih.gov/pubmed/15668446?dopt=Abstract)
- Korhonen JA, Pande V, Holmlund T, Farge G, Pham XH, Nilsson L, Falkenberg M. Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia. J Mol Biol. 2008 Mar 28;377(3):691-705. doi: 10.1016/j.jmb.2008.01.035. Epub 2008 Jan 26. (http://www.ncbi.nlm.nih.gov/pubmed/18279890?dopt=Abstract)
- Lönnqvist T, Paetau A, Valanne L, Pihko H. Recessive twinkle mutations cause severe epileptic encephalopathy. Brain. 2009 Jun;132(Pt 6):1553-62. doi: 10.1093/brain/awp045. Epub 2009 Mar 20. (http://www.ncbi.nlm.nih.gov/pubmed/19304794?dopt=Abstract)
- Morino H, Pierce SB, Matsuda Y, Walsh T, Ohsawa R, Newby M, Hiraki-Kamon K, Kuramochi M, Lee MK, Klevit RE, Martin A, Maruyama H, King MC, Kawakami H. Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features. Neurology. 2014 Nov 25;83(22):2054-61. doi: 10.1212/WNL.0000000000001036. Epub 2014 Oct 29. (http://www.ncbi.nlm.nih.gov/pubmed/25355836?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/56652)
- Nikali K, Suomalainen A, Saharinen J, Kuokkanen M, Spelbrink JN, Lönnqvist T, Peltonen L. Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. Hum Mol Genet. 2005 Oct 15;14(20):2981-90. Epub 2005 Aug 31. (http://www.ncbi.nlm.nih.gov/pubmed/16135556?dopt=Abstract)
- Spelbrink JN, Li FY, Tiranti V, Nikali K, Yuan QP, Tariq M, Wanrooij S, Garrido N, Comi G, Morandi L, Santoro L, Toscano A, Fabrizi GM, Somer H, Croxen R, Beeson D, Poulton J, Suomalainen A, Jacobs HT, Zeviani M, Larsson C. Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nat Genet. 2001 Jul;28(3):223-31. Erratum in: Nat Genet 2001 Sep;29(1):100. (http://www.ncbi.nlm.nih.gov/pubmed/11431692?dopt=Abstract)
- Van Goethem G, Martin JJ, Van Broeckhoven C. Progressive external ophthalmoplegia characterized by multiple deletions of mitochondrial DNA: unraveling the pathogenesis of human mitochondrial DNA instability and the initiation of a genetic classification. Neuromolecular Med. 2003;3(3):129-46. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12835509?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.