Ask about this productRelated genes to: PEO1 antibody
- Gene:
- TWNK NIH gene
- Name:
- twinkle mtDNA helicase
- Previous symbol:
- IOSCA, C10orf2
- Synonyms:
- PEO, PEO1, TWINKLE, FLJ21832, TWINL
- Chromosome:
- 10q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 2000-08-11
- Date modifiied:
- 2016-10-11
Related products to: PEO1 antibody
Related articles to: PEO1 antibody
- Perrault syndrome (PS) is a rare autosomal-recessive disorder characterized by bilateral sensorineural hearing loss, ovarian dysgenesis in females, and variable neurological impairment. Pathogenic variants in TWNK, encoding the mitochondrial helicase Twinkle, disrupt mtDNA maintenance and underlie a subset of PS cases. Here, we generated the first mouse models carrying patient-specific TWNK missense mutations c.814G > A (p.Ala272Thr) and c.1166C > T (p.Ala389Val), both in homozygosity and compound heterozygosity, using CRISPR/Cas9 editing. Mutant mice exhibit profound hearing loss, locomotor hypoactivity, and axonal peripheral neuropathy, while overall growth remains normal. Molecular assays reveal a significant reduction in mtDNA copy number and ATP content in muscle and brain, accompanied by impaired respiratory-chain function. These phenotypes faithfully recapitulate core features of human PS, establishing a genetically precise in vivo platform to dissect disease mechanisms and to evaluate targeted therapies for mitochondrial dysfunction and sensorineural hearing loss. - Source: PubMed
Publication date: 2026/02/28
Wang WeiDong XiangCao Chun-YuLi Hong-BoLv Ya-Feng - We generated an induced pluripotent stem cell (iPSC) line, designated CTGUi002-A, from peripheral blood mononuclear cells (PBMCs) of a 9-year-old female with Perrault syndrome carrying biallelic TWNK mutations (c.811G>A and c.1163C>T), using Sendai virus-mediated delivery of OCT4, SOX2, KLF4, and c-MYC. The CTGUi002-A iPSC line retained the TWNK mutations and exhibited characteristic iPSC morphology, expressed pluripotency markers, maintained a normal karyotype, and demonstrated trilineage differentiation potential. - Source: PubMed
Publication date: 2026/02/15
Wu Shen-LinLi YangDou TonghaiWang WeiZhan Jing-QiongLv Ya-Feng - Twinkle is the sole replicative helicase in human mitochondria, essential for mitochondrial DNA replication. Beyond its canonical unwinding activity, Twinkle has non-canonical activities, including DNA annealing and strand-exchange. Here, we show that these non-canonical activities extend to RNA. Twinkle binds RNA and catalyzes RNA:DNA hybrid formation through annealing, strand-exchange, and toehold-mediated strand displacement. Twinkle can unwind RNA:DNA forks when loaded onto the DNA tail but not the RNA tail. Although the physiological role of these RNA-related activities remains unclear, we show that Twinkle can strand-exchange an RNA downstream of a stalled replication fork to restart replication. The annealing/strand-exchange activity can be involved in DNA replication initiation and repair, but RNA:DNA hybrids can compromise genome integrity, emphasizing the need to balance unwinding and annealing activities. Interestingly, mitochondrial SSB inhibits the RNA:DNA annealing activity of Twinkle, thus regulating the non-canonical functions of Twinkle. A disease-associated W315L variant, which is defective in DNA replication, retains annealing and strand-exchange functions with both RNA and DNA, resulting in an imbalance between replication and annealing functions that may underlie its pathogenicity. Our findings of Twinkle's RNA-binding and strand-exchange activities may have a connection to its localization within mitochondrial RNA granules. - Source: PubMed
Singh AnupamJohnson Laura CBaruch-Torres NoeYin Y WhitneyPatel Smita S - Twinkle, encoded by the gene, is a mitochondrial DNA helicase that unwinds the double helix of DNA during replication, playing a pivotal role in mitochondrial function. Twinkle-related disorders encompass a variety of genetic disorders characterized by mitochondrial dysfunction. Although several phenotypes have been described, the full clinical and molecular spectrum remains poorly defined. The aim of this study was to characterize the phenotypic and genotypic variability among multinational patients diagnosed with Twinkle-related disorders. - Source: PubMed
Publication date: 2026/01/15
Lopriore PiervitoÜnlütürk ZeynepKlopstock ThomasKaraa AmelRouzier CecileDomínguez-González CristinaLamperti CostanzaMancuso Michelangelo Cecchi GiuliaMontano VincenzoSiciliano GabrieleNicoletta ValeriaMaioli MariantoniettaPrimiano GuidoServidei SerenellaLa Morgia ChiaraCarelli ValerioValentino Maria LuciaCaporali LeonardoArena Ignazio GiuseppeMusumeci OlimpiaLopergolo DiegoMalandrini AlessandroGallus Gian NicolaFilosto MassimilianoBello LucaPegoraro ElenaComi Giacomo PietroMagri FrancescaRonchi DarioDi Fonzo AlessioPercetti MarcoAzzimonti MatteoBüchner BorianaProkisch HolgerBermejo-Guerrero LauraProcaccio VincentGaignard PaulineEchaniz-Laguna AndoniSchiff ManuelRötig AgnèsToutain AnnickPaquis-Flucklinger VéroniqueMorel GodelieveRobin StéphanieNadaj-Pakleza AleksandraChanson Jean-BaptisteChaussenot AnnabelleAit-El-Mkadem Saadi SamiraTrimouille AurélienTranchant ChristineSalort-Campana EmmanuelleBieth EricSacconi SabrinaDuval FannyRestrepo Vera Juan LuisMolnar Maria JuditVissing JohnHaas RichardLarson AustinEnns Gregory MParikh SumitGoldstein AmyHirano Michio - The quantitative content of mitochondrial DNA (mtDNA) - a multicopy circular genome - is an important parameter relevant for function of mitochondrial oxidative phosphorylation (OxPhos) in cells, since mtDNA encodes 13 essential OxPhos proteins, 22 tRNAs, and 2 rRNAs. In contrast to the nuclear genome, where almost all lesions have to be repaired, the multicopy nature of mtDNA allows the degradation of severely damaged genomes. Therefore, cellular mtDNA maintenance and its copy number not only depend on replication speed and repair reactions. The speed of intramitochondrial mtDNA degradation performed by a POLGexo/MGME1/TWNK degradation complex and the breakdown rate of entire mitochondria (mitophagy) are also relevant for maintaining the required steady state levels of mtDNA. The present review discusses available information about the processes relevant for turnover of mitochondrial DNA, which dysbalance leads to mtDNA maintenance disorders. This group of mitochondrial diseases is defined by pathological decrease of cellular mtDNA copy number and can be separated in diseases related to decreased mtDNA synthesis rates (due to direct replication defects or mitochondrial nucleotide pool dysbalance) or diseases related to increased breakdown of entire mitochondria (due to elevated mitophagy rates). - Source: PubMed
Kunz Wolfram S