Twinkle Protein, Mitochondrial (TWINL)

PEO; SANDO; PEOA3; PEO1; IOSCA; SCA8; Progressive External Ophthalmoplegia 1; Infantile Onset Spinocerebellar Ataxia; T7 gp4-like with intramitochondrial nucleoid localization

SPN	U137
HGNC	1160
MGI	2137410
PubMed	16612544
RGD	1307884
UniProt	Q96RR1
Wiki	PEO1

Twinkle is a mitochondrial protein with structural similarity to the phage T7 primase/helicase (GP4) and other hexameric ring helicases. The twinkle protein a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Reference

"Human mitochondrial DNA deletions associated with mutations in the gene for Twinkle, a phage T7 gene 4-like protein localized in mitochondria."
Nat. Genet. 28:223-231(2001) [PubMed] [Europe PMC] [Abstract]

Erratum
Nat. Genet. 29:100-100(2001)

"The full-ORF clone resource of the German cDNA consortium."
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 10."
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"TWINKLE has 5' -> 3' DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein."
J. Biol. Chem. 278:48627-48632(2003) [PubMed] [Europe PMC] [Abstract]

"Reconstitution of a minimal mtDNA replisome in vitro."
EMBO J. 23:2423-2429(2004) [PubMed] [Europe PMC] [Abstract]

"Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number."
Hum. Mol. Genet. 13:3219-3227(2004) [PubMed] [Europe PMC] [Abstract]

"Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA."
Nucleic Acids Res. 32:3053-3064(2004) [PubMed] [Europe PMC] [Abstract]

"Clinical and molecular features of adPEO due to mutations in the Twinkle gene."
J. Neurol. Sci. 201:39-44(2002) [PubMed] [Europe PMC] [Abstract]

"The V368I mutation in Twinkle does not segregate with AdPEO."
Ann. Neurol. 53:278-278(2003) [PubMed] [Europe PMC] [Abstract]

"Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle."
Hum. Mutat. 22:175-176(2003) [PubMed] [Europe PMC] [Abstract]

"Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO)."
Neurology 60:1354-1356(2003) [PubMed] [Europe PMC] [Abstract]

"A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia."
Neuromuscul. Disord. 13:568-572(2003) [PubMed] [Europe PMC] [Abstract]

"Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky."
Hum. Mol. Genet. 14:2981-2990(2005) [PubMed] [Europe PMC] [Abstract]

"Sensory ataxic neuropathy due to a novel C10Orf2 mutation with probable germline mosaicism."
Neurology 64:371-373(2005) [PubMed] [Europe PMC] [Abstract]

"Molecular analysis of ANT1, TWINKLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay."
Eur. J. Hum. Genet. 14:917-922(2006) [PubMed] [Europe PMC] [Abstract]

"Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion."
Ann. Neurol. 62:579-587(2007) [PubMed] [Europe PMC] [Abstract]

"Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion."
Brain 130:3032-3040(2007) [PubMed] [Europe PMC] [Abstract]

"Mild ocular myopathy associated with a novel mutation in mitochondrial twinkle helicase."
Neuromuscul. Disord. 17:677-680(2007) [PubMed] [Europe PMC] [Abstract]

"Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia."
J. Neurol. 255:1384-1391(2008) [PubMed] [Europe PMC] [Abstract]

"Phenotype and clinical course in a family with a new de novo Twinkle gene mutation."
Neuromuscul. Disord. 18:306-309(2008) [PubMed] [Europe PMC] [Abstract]

"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."
Am. J. Med. Genet. A 149:861-867(2009) [PubMed] [Europe PMC] [Abstract]

"Molecular analysis in a family presenting with a mild form of late-onset autosomal dominant chronic progressive external ophthalmoplegia."
Neuromuscul. Disord. 19:423-426(2009) [PubMed] [Europe PMC] [Abstract]

"Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure."
Neuromuscul. Disord. 19:845-848(2009) [PubMed] [Europe PMC] [Abstract]

"The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO."
Neurology 74:1619-1626(2010) [PubMed] [Europe PMC] [Abstract]

"TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review."
Eur. J. Neurol. 18:436-441(2011) [PubMed] [Europe PMC] [Abstract]

"Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing."
Pediatr. Neurol. 46:172-177(2012) [PubMed] [Europe PMC] [Abstract]

"Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features."
Neurology 83:2054-2061(2014) [PubMed] [Europe PMC] [Abstract]