Property Summary

NCBI Gene PubMed Count 69
PubMed Score 144.61
PubTator Score 134.05

Knowledge Summary


No data available


  Disease (7)


  Differential Expression (7)

Disease log2 FC p
malignant mesothelioma 1.200 4.5e-06
osteosarcoma -1.295 4.9e-05
medulloblastoma, large-cell 1.900 3.4e-05
non-small cell lung cancer 1.022 1.4e-11
lung cancer 2.300 5.9e-04
colon cancer 2.500 3.3e-08
group 3 medulloblastoma 1.700 1.1e-04

Gene RIF (47)

26838077 We identified a missense mutation in c10orf2 in an Iranian family with an association to progressive external ophthalmoplegia, myopathy, dysphagia, dysphonia, and behavior change. Early death was also a novel feature in affected family members.
26689116 sequencing coding regions of C10orf2 revealed three variants in three different patients, of which two were novel (c.1964G>A/p.G655D; c.204G>A/p.G68G) variants and one was reported (c.1052A>G/p. N351S).
25824949 An electron microscopy model of Twinkle reveals a hexameric two-layered ring comprising the zinc-binding domain and RNA polymerase domain in one layer and the RecA-like hexamerization C-terminal domain in another.
25355836 Mutations in Twinkle were linked to Perrault syndrome with neurologic features.
25193669 The mitochondrial replicative helicase Twinkle inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate.
24816431 Identified compound heterozygous mutations of the C10orf2 gene as the cause of infantile-onset spinocerebellar ataxia with sensorimotor polyneuropathy and myopathy.
24524965 Mitochondrial DNA (mtDNA) content plays an important role in energy production and sustaining normal physiological function.
24218554 Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species.
24018892 16-year follow-up of autosomal dominant progressive external ophthalmoplegia (adPEO) due to the p.R357P gene mutation in PEO1; adPEO due to this mutation is a late-onset ocular myopathy beginning with ptosis and progressing slowly; ophthalmoparesis, if present, is mild
23375728 A homozygous mutation in TWINKLE is the cause of multisystemic failure including renal tubulopathy in three consanguinity siblings.
22952820 Overexpression of d-mtDNA helicase containing either the K388A or A442P mutations causes a mitochondrial oxidative phosphorylation (OXPHOS) defect that significantly reduces cell proliferation.
22580846 analysis did not reveal disease causing POLG or PEO1 mutations in patients with atypical parkinsonism
22383523 the strand annealing activity of TWINKLE may play a role in recombination-mediated replication initiation found in the mitochondria of mammalian brain and heart or in replication fork regression during repair of damaged DNA replication forks.
22353293 A novel homozygous missense mutation c.1366C>G (L456V) in C10orf2 (the Twinkle gene) was identified in a family with infantile onset spinocerebellar ataxia.
21689831 PEO1 sequencing discloses novel mutations in exons 1 and 4 of the gene in chronic external ophthalmoplegia; this is the first report of a mutation occurring in exon 4.
21540127 Multimeric unicircular mtDNA molecules are seen in cells expressing Twinkle.
20880070 We present a new French family of whom two members displayed autosomal dominant progressive external ophthalmoplegia associated with the R374Q mutation of the Twinkle gene
20877624 Observational study of gene-disease association. (HuGE Navigator)
20659899 Disease variants of the human mitochondrial DNA helicase encoded by C10orf2 differentially alter protein stability, nucleotide hydrolysis, and helicase activity.
20479361 Our data suggest a shared clinical phenotype with variable mild multiorgan involvement, and that the contribution of PEO1 mutations as a cause of autosomal dominant progressive external ophthalmoplegia may well be underestimated.
20181062 Observational study of gene-disease association. (HuGE Navigator)
19853444 study of a Saudi Arabian family with autosomal dominant progressive external ophthalmoplegia & late onset multi-organ failure caused by a novel PEO1/Twinkle mutation (1078C > G + 1079T > G double nucleotide change predicting a Leu360Gly substitution)
19513767 Twinkle variations in the linker domain alter cerebral function and further implicate disrupted mitochondrial DNA integrity in the pathogenesis of dementia
19428252 heterozygous c.907C>T (p.R303W) mutation found in the N-terminal domain of the human mitochondrial DNA helicase, Twinkle protein, associated with phenotypically mild autosomal dominant progressive external ophthalmoplegia
19425506 Association of the T(-365)C POLG1, G(-25)A ANT1 and G(-605)T PEO1 gene polymorphisms with diabetic polyneuropathy in patients with type 1 diabetes mellitus
19425506 Observational study of gene-disease association. (HuGE Navigator)
18989381 This study widens the mutation spectrum of PEO1 and is the first to report the PEO1 mutation in the Chinese population.
18973250 A heterozygous mutation predicting a R334Q substitution in Twinkle was associated with progressive external opthalmoplegia and/or Parkinsonism in several members of a family.
18971204 MtDNA replication pausing is the consequence of Twinkle mutations that predisposes to progressive external ophthalmoplegia.
18575922 Data show that PEO1 has a major role in determining familial progressive external ophthalmoplegia.
18575922 Observational study of gene-disease association. (HuGE Navigator)
18396044 We describe a new de novo mutation (1110C>A) in the PEO1 gene in patients with Ophthalmoplegia, Chronic Progressive External in a mother and her two sons.
18039713 The N-terminal part of TWINKLE is required for efficient binding to single-stranded DNA.
17921179 study reports a new phenotype in two siblings with compound heterozygous Twinkle mutations (A318T and Y508C), characterized by severe early onset encephalopathy and signs of liver involvement
17722119 Identifying other Twinkle mutations in mitochondrial DNA depletion and/or autosomal dominant progressive external ophthalmoplegia and studying their impact on proteins should help in understanding why some mutations are recessive and others are dominant.
17620490 This finding broadens the clinical spectrum of Twinkle gene mutations and further implicates loss of mitochondrial DNA integrity in the pathogenesis of Parkinson disease.
17614277 We report a Spanish family showing a mild phenotype characterized by autosomal dominant ocular myopathy and morphological signs of mitochondrial dysfunction, that harboured a novel(p.R357P) mutation in the hot-spot linker region of the twinkle protein.
17614276 Direct sequencing showed a heteroplasmic mutation at nucleotide 7506 in the dihydrouridine stem of the tRNA(Ser(UCN)) gene.
17420318 Observational study of gene-disease association. (HuGE Navigator)
17324440 Mitochondrial DNA helicase belongs to the DnaB-like family of replicative DNA helicases.
16385451 Observational study of gene-disease association. (HuGE Navigator)
16135556 the severe neurological phenotype observed in infantile onset spinocerebellar ataxia, suggests that the mutated Twinky and Twinkle play a crucial role in the maintenance and/or function of specific affected neuronal subpopulations [twinky]
15668446 A novel heterozygous A to G transition at nucleotide 955 of C10Orf2 (Twinkle)ws found in siblings with sensory ataxic neuropathy.
15181170 mechanism whereby mutations in twinkle result in progressive accumulation of multiple mtDNA deletions in post- mitotic tissues
12872260 A novel PEO1 mutation in a sporadic PEO patient with multiple mtDNA deletions.
12686611 both the mitochondrial transcription factor TFAM and mitochondrial single-stranded DNA-binding protein colocalize with Twinkle in intramitochondrial foci
12163192 Twinkle appears to be the most common gene associated with adPEO in Australian families.

AA Sequence


Text Mined References (71)

PMID Year Title
26838077 2016 Mutation in TWINKLE in a Large Iranian Family with Progressive External Ophthalmoplegia, Myopathy, Dysphagia and Dysphonia, and Behavior Change.
26689116 2016 Novel mutation in C10orf2 associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging.
25824949 2015 The hexameric structure of the human mitochondrial replicative helicase Twinkle.
25355836 2014 Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features.
25193669 2014 DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase.
24816431 2014 Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy.
24524965 2014 Mitochondrial DNA content contributes to healthy aging in Chinese: a study from nonagenarians and centenarians.
24218554 2013 Overexpression of Twinkle-helicase protects cardiomyocytes from genotoxic stress caused by reactive oxygen species.
24018892 2013 Longitudinal clinical follow-up of a large family with the R357P Twinkle mutation.
23375728 2013 Exome sequencing reveals a homozygous mutation in TWINKLE as the cause of multisystemic failure including renal tubulopathy in three siblings.
22952820 2012 Modeling pathogenic mutations of human twinkle in Drosophila suggests an apoptosis role in response to mitochondrial defects.
22580846 2012 POLG and PEO1 (Twinkle) mutations are infrequent in PSP-like atypical parkinsonism: a preliminary screening study.
22383523 2012 Human mitochondrial DNA helicase TWINKLE is both an unwinding and annealing helicase.
22353293 2012 Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing.
21689831 2011 Two novel mutations in PEO1 (twinkle) gene associated with chronic external ophthalmoplegia.
21540127 2011 Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells.
20880070 2011 TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review.
20877624 2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
20843780 2011 Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.
20659899 2010 Disease variants of the human mitochondrial DNA helicase encoded by C10orf2 differentially alter protein stability, nucleotide hydrolysis, and helicase activity.
20479361 2010 The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO.
20181062 2010 Mitochondrial DNA haplogroups in early-onset Alzheimer's disease and frontotemporal lobar degeneration.
19853444 2009 Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure.
19513767 2010 A novel variation in the Twinkle linker region causing late-onset dementia.
19428252 2009 Molecular analysis in a family presenting with a mild form of late-onset autosomal dominant chronic progressive external ophthalmoplegia.
19425506 [Association of the T(-365)C POLG1, G(-25)A ANT1 and G(-605)T PEO1 gene polymorphisms with diabetic polyneuropathy in patients with type 1 diabetes mellitus].
19353676 2009 Finding twinkle in the eyes of a 71-year-old lady: a case report and review of the genotypic and phenotypic spectrum of TWINKLE-related dominant disease.
19304794 2009 Recessive twinkle mutations cause severe epileptic encephalopathy.
18989381 2008 A novel Twinkle (PEO1) gene mutation in a Chinese family with adPEO.
18973250 2009 Neurodegenerative Parkinsonism and progressive external ophthalmoplegia with a Twinkle mutation.
18971204 2009 Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling.
18708037 2008 SCA8 mRNA expression suggests an antisense regulation of KLHL1 and correlates to SCA8 pathology.
18575922 2008 Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia.
18396044 2008 Phenotype and clinical course in a family with a new de novo Twinkle gene mutation.
18063578 2008 The layered structure of human mitochondrial DNA nucleoids.
18039713 2008 The N-terminal domain of TWINKLE contributes to single-stranded DNA binding and DNA helicase activities.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17921179 2007 Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion.
17722119 2007 Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion.
17620490 2007 Familial parkinsonism and ophthalmoplegia from a mutation in the mitochondrial DNA helicase twinkle.
17614277 2007 Mild ocular myopathy associated with a novel mutation in mitochondrial twinkle helicase.
17614276 2007 A novel heteroplasmic tRNA(Ser(UCN)) mtDNA point mutation associated with progressive external ophthalmoplegia and hearing loss.
17420318 2007 Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism.
17324440 2007 Modular architecture of the hexameric human mitochondrial DNA helicase.
16712791 2006 Identification of intrahepatic cholangiocarcinoma related genes by comparison with normal liver tissues using expressed sequence tags.
16639411 2006 Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay.
16385451 2006 A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16135556 2005 Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky.
15668446 2005 Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism.
15509589 2004 Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15181170 2004 Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA.
15167897 2004 Reconstitution of a minimal mtDNA replisome in vitro.
15164054 2004 The DNA sequence and comparative analysis of human chromosome 10.
14739292 2004 DNA and RNA binding by the mitochondrial lon protease is regulated by nucleotide and protein substrate.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12975372 2003 TWINKLE Has 5' -> 3' DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein.
12921794 2003 A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia.
12872260 2003 Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle.
12707443 2003 Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).
12686611 2003 Composition and dynamics of human mitochondrial nucleoids.
12557300 2003 The V368i mutation in Twinkle does not segregate with AdPEO.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12163192 2002 Clinical and molecular features of adPEO due to mutations in the Twinkle gene.
11756592 2001 ANT1, Twinkle, POLG, and TP: new genes open our eyes to ophthalmoplegia.
11431692 2001 Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria.
10645945 2000 The bacterial replicative helicase DnaB evolved from a RecA duplication.
9027505 1997 Toward cloning of a novel ataxia gene: refined assignment and physical map of the IOSCA locus (SCA8) on 10q24.
7726163 1995 Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus.
7719341 1995 An autosomal locus predisposing to deletions of mitochondrial DNA.