twinkle mtDNA helicase
Last updated 18 Aug 2020
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The TWNK 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.
Normal function
The TWNK 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.
Conditions referring to this gene or chromosome
Other names
C10orf2
chromosome 10 open reading frame 2
PEO1
PEO1_HUMAN
progressive external ophthalmoplegia 1 protein
T7 gp4-like protein with intramitochondrial nucleoid localization
T7-like mitochondrial DNA helicase
twinkle
Further reading and references
- twinkle mtDNA helicase; MedlinePlus, National Library of Medicine.
- Bermejo-Guerrero L, de Fuenmayor-Fernandez de la Hoz CP, Serrano-Lorenzo P, Blazquez-Encinar A, Gutierrez-Gutierrez G, Martinez-Vicente L, Galan-Davila L, Garcia-Garcia J, Arenas J, Muelas N, Hernandez-Lain A, Dominguez-Gonzalez C, Martin MA. Clinical, Histological, and Genetic Features of 25 Patients with Autosomal Dominant Progressive External Ophthalmoplegia (ad-PEO)/PEO-Plus Due to TWNK Mutations. J Clin Med. 2021 Dec 22;11(1):22. doi: 10.3390/jcm11010022.
- El-Hattab AW, Craigen WJ, Wong LJC, Scaglia F. Mitochondrial DNA Maintenance Defects Overview. 2018 Mar 8. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK487393/
- Fratter C, Gorman GS, Stewart JD, Buddles M, Smith C, Evans J, Seller A, Poulton J, Roberts M, Hanna MG, Rahman S, Omer SE, Klopstock T, Schoser B, Kornblum C, Czermin B, Lecky B, Blakely EL, Craig K, Chinnery PF, Turnbull DM, Horvath R, Taylor RW. The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO. Neurology. 2010 May 18;74(20):1619-26. doi: 10.1212/WNL.0b013e3181df099f.
- Hakonen AH, Goffart S, Marjavaara S, Paetau A, Cooper H, Mattila K, Lampinen M, Sajantila A, Lonnqvist 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.
- Johnson LC, Singh A, Patel SS. The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase gamma. J Biol Chem. 2023 Jan;299(1):102797. doi: 10.1016/j.jbc.2022.102797. Epub 2022 Dec 14.
- 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.
- Li T, Faridi R, Newman WG, Friedman TB. Perrault Syndrome Overview. 2014 Sep 25 [updated 2025 May 8]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK242617/
- Longley MJ, Humble MM, Sharief FS, Copeland WC. Disease variants of the human mitochondrial DNA helicase encoded by C10orf2 differentially alter protein stability, nucleotide hydrolysis, and helicase activity. J Biol Chem. 2010 Sep 24;285(39):29690-702. doi: 10.1074/jbc.M110.151795. Epub 2010 Jul 20.
- Lonnqvist 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.
- Lopriore P, Unluturk Z, Klopstock T, Karaa A, Rouzier C, Dominguez-Gonzalez C, Lamperti C, Mancuso M; Twinkle-Related Disorders International Consortium for Trial Readiness (TReDIC); Cecchi G, Montano V, Siciliano G, Nicoletta V, Maioli M, Primiano G, Servidei S, La Morgia C, Carelli V, Valentino ML, Caporali L, Arena IG, Musumeci O, Lopergolo D, Malandrini A, Gallus GN, Filosto M, Bello L, Pegoraro E, Comi GP, Magri F, Ronchi D, Di Fonzo A, Percetti M, Azzimonti M, Buchner B, Prokisch H, Bermejo-Guerrero L, Procaccio V, Gaignard P, Echaniz-Laguna A, Schiff M, Rotig A, Toutain A, Paquis-Flucklinger V, Morel G, Robin S, Nadaj-Pakleza A, Chanson JB, Chaussenot A, Ait-El-Mkadem Saadi S, Trimouille A, Tranchant C, Salort-Campana E, Bieth E, Sacconi S, Duval F, Restrepo Vera JL, Molnar MJ, Vissing J, Haas R, Larson A, Enns GM, Parikh S, Goldstein A, Hirano M. Clinical and Genotypic Spectrum of Twinkle-Related Disorders: Insights From a Multinational Cohort Study. Neurology. 2026 Feb 10;106(3):e214401. doi: 10.1212/WNL.0000000000214401. Epub 2026 Jan 15.
- 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.
- Nikali K, Suomalainen A, Saharinen J, Kuokkanen M, Spelbrink JN, Lonnqvist 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. doi: 10.1093/hmg/ddi328. Epub 2005 Aug 31.
- Singh A, Johnson LC, Baruch-Torres N, Yin YW, Patel SS. Human mitochondrial helicase Twinkle has RNA binding, annealing, and strand-exchange activities. Nucleic Acids Res. 2026 Jan 14;54(2):gkag008. doi: 10.1093/nar/gkag008.
- 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. doi: 10.1038/90058.
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