Stanford Home
Ovarian Kaleidoscope Database (OKdb)



Transgenic Mouse Models



Hsueh lab


since 01/2001:

twinkle mtDNA helicase OKDB#: 5529
 Symbols: TWNK Species: human
 Synonyms: PEO, PEO1, SCA8, ATXN8, IOSCA, PEOA3, SANDO, TWINL, MTDPS7, PRLTS5, C10orf2  Locus: 10q24.31 in Homo sapiens

For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
Mammalian Reproductive Genetics   Endometrium Database Resource   Orthologous Genes   UCSC Genome Browser   GEO Profiles new!   Amazonia (transcriptome data) new!


DNA Microarrays
link to BioGPS
General Comment The TWNK gene encodes a mitochondrial protein with structural similarity to the phage T7 primase/helicase (GP4) and other hexameric ring helicases. The twinkle protein colocalizes with mtDNA in mitochondrial nucleoids, a

NCBI Summary: This gene encodes 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.[provided by RefSeq, Aug 2009]
General function
Cellular localization Mitochondrial
Ovarian function
Expression regulated by
Ovarian localization Oocyte, Granulosa
Follicle stages
Phenotypes POF (premature ovarian failure)
Mutations 1 mutations

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Novel neuro-audiological findings and further evidence for TWNK involvement in Perrault syndrome. Ołdak M et al. (2017) Hearing loss and ovarian dysfunction are key features of Perrault syndrome (PRLTS) but the clinical and pathophysiological features of hearing impairment in PRLTS individuals have not been addressed. Mutations in one of five different genes HSD17B4, HARS2, LARS2, CLPP or TWNK (previous symbol C10orf2) cause the autosomal recessive disorder but they are found only in about half of the patients. We report on two siblings with a clinical picture resembling a severe, neurological type of PRLTS. For an exhaustive characterisation of the phenotype neuroimaging with volumetric measurements and objective measures of cochlear hair cell and auditory nerve function (otoacustic emissions and auditory brainstem responses) were used. Whole exome sequencing was applied to identify the genetic cause of the disorder. Co-segregation of the detected mutations with the phenotype was confirmed by Sanger sequencing. In silico analysis including 3D protein structure modelling was used to predict the deleterious effects of the detected variants on protein function. We found two rare biallelic mutations in TWNK, encoding Twinkle, an essential mitochondrial helicase. Mutation c.1196A>G (p.Asn399Ser) recurred for the first time in a patient with PRLTS and the second mutation c.1802G>A (p.Arg601Gln) was novel for the disorder. In both patients neuroimaging studies showed diminished cervical enlargement of the spinal cord and for the first time in PRLTS partial atrophy of the vestibulocochlear nerves and decreased grey and increased white matter volumes of the cerebellum. Morphological changes in the auditory nerves, their desynchronized activity and partial cochlear dysfunction underlay the complex mechanism of hearing impairment in the patients. Our study unveils novel features on the phenotypic landscape of PRLTS and provides further evidence that the newly identified for PRLTS TWNK gene is involved in its pathogenesis.//////////////////

Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
OMIM \ Animal Model
KEGG Pathways
Recent Publications
Search for Antibody

created: Jan. 2, 2018, 12:38 p.m. by: system   email:
home page:
last update: June 9, 2021, 2:16 p.m. by: hsueh    email:

Use the back button of your browser to return to the Gene List.

Click here to return to gene search form