Human Gene TWNK (uc001ksf.2)
  Description: Homo sapiens chromosome 10 open reading frame 2 (TWNK), transcript variant 1, mRNA.
RefSeq Summary (NM_021830): 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].
Transcript (Including UTRs)
   Position: hg19 chr10:102,747,293-102,754,158 Size: 6,866 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr10:102,747,968-102,753,267 Size: 5,300 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:102,747,293-102,754,158)mRNA (may differ from genome)Protein (684 aa)
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H-INVHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeTreefamUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PEO1_HUMAN
DESCRIPTION: RecName: Full=Twinkle protein, mitochondrial; EC=3.6.4.12; AltName: Full=Progressive external ophthalmoplegia 1 protein; AltName: Full=T7 gp4-like protein with intramitochondrial nucleoid localization; AltName: Full=T7-like mitochondrial DNA helicase; Flags: Precursor;
FUNCTION: Involved in mitochondrial DNA (mtDNA) metabolism. Could function as an adenine nucleotide-dependent DNA helicase. Function inferred to be critical for lifetime maintenance of mtDNA integrity. In vitro, forms in combination with POLG, a processive replication machinery, which can use double-stranded DNA (dsDNA) as template to synthesize single-stranded DNA (ssDNA) molecules. May be a key regulator of mtDNA copy number in mammals.
CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
SUBUNIT: Forms multimers in vitro, including hexamers. Interacts with POLG in vitro.
SUBCELLULAR LOCATION: Mitochondrion matrix, mitochondrion nucleoid. Note=Colocalizes with mtDNA in mitochondrial nucleoids, a nucleoproteins complex consisting of a number of copies of proteins associated with mtDNA, probably involved in mtDNA maintenance and expression.
TISSUE SPECIFICITY: High relative levels in skeletal muscle, testis and pancreas. Lower levels of expression in the heart, brain, placenta, lung, liver, kidney, spleen, thymus, prostate, ovary, small intestine, colon and leukocytes. Expression is coregulated with MRPL43.
DISEASE: Defects in PEO1 are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 3 (PEOA3) [MIM:609286]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged- red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
DISEASE: Defects in PEO1 are a cause of sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]. SANDO is a clinically heterogeneous systemic disorder with variable features resulting from mitochondrial dysfunction. It shares phenotypic characteristics with autosomal recessive progressive external ophthalmoplegia and mitochondrial neurogastrointestinal encephalopathy syndrome. The clinical triad of symptoms consists of sensory ataxic, neuropathy, dysarthria, and ophthalmoparesis.
DISEASE: Defects in PEO1 are the cause of mitochondrial DNA depletion syndrome type 7 (MTDPS7) [MIM:271245]; also known as spinocerebellar ataxia infantile-onset (IOSCA). A severe disease associated with mitochondrial dysfunction. Some patients are affected by progressive atrophy of the cerebellum, brain stem, the spinal cord, and sensory axonal neuropath. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. Some individuals manifest a hepatocerebral phenotype characterized by liver insufficiency, increased serum and CSF lactate, hypotonia, psychomotor retardation and peripheral neuropathy.
SIMILARITY: Contains 1 SF4 helicase domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/C10orf2";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/peo1/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TWNK
Diseases sorted by gene-association score: mitochondrial dna depletion syndrome 7* (1697), progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3* (1333), perrault syndrome 5* (1329), twnk-related mitochondrial dna depletion syndrome, hepatocerebral form* (500), mitochondrial dna depletion syndrome, hepatocerebrorenal form* (350), mitochondrial recessive ataxia syndrome* (301), mitochondrial dna depletion syndrome 3* (283), autosomal dominant progressive external ophthalmoplegia* (185), perrault syndrome* (177), twnk-related ataxia neuropathy spectrum disorders* (100), chronic progressive external ophthalmoplegia (39), athetosis (13), spinocerebellar ataxia 8 (8), axonal neuropathy (8), diabetic polyneuropathy (7), mitochondrial dna depletion syndrome 4a (7), baller-gerold syndrome (7), warsaw breakage syndrome (6), ataxia (5), 3-methylglutaconic aciduria, type v (5), hereditary ataxia (5), kearns-sayre syndrome (5), ocular motility disease (5), mitochondrial disorders (5), myoclonic epilepsy associated with ragged-red fibers (4), myopathy (2)
* = Manually curated disease association

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.60 RPKM in Testis
Total median expression: 155.52 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -216.40675-0.321 Picture PostScript Text
3' UTR -311.09891-0.349 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007694 - DNA_helicase_DnaB-like_C

Pfam Domains:
PF03796 - DnaB-like helicase C terminal domain
PF06745 - KaiC
PF13481 - AAA domain

SCOP Domains:
52540 - P-loop containing nucleoside triphosphate hydrolases
53795 - PEP carboxykinase-like

ModBase Predicted Comparative 3D Structure on Q96RR1
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  EnsemblFlyBaseWormBase 
  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0002020 protease binding
GO:0003678 DNA helicase activity
GO:0003697 single-stranded DNA binding
GO:0004386 helicase activity
GO:0005524 ATP binding
GO:0016787 hydrolase activity
GO:0043139 5'-3' DNA helicase activity

Biological Process:
GO:0006260 DNA replication
GO:0006264 mitochondrial DNA replication
GO:0006268 DNA unwinding involved in DNA replication
GO:0006390 transcription from mitochondrial promoter
GO:0007005 mitochondrion organization
GO:0034214 protein hexamerization
GO:0051260 protein homooligomerization
GO:0071333 cellular response to glucose stimulus

Cellular Component:
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0042645 mitochondrial nucleoid


-  Descriptions from all associated GenBank mRNAs
  AK308098 - Homo sapiens cDNA, FLJ98046.
AK297068 - Homo sapiens cDNA FLJ50799 complete cds, highly similar to Twinkle protein, mitochondrial precursor (EC 3.6.1.-).
BX640829 - Homo sapiens mRNA; cDNA DKFZp686O01205 (from clone DKFZp686O01205).
AF292004 - Homo sapiens putative T7-like mitochondrial DNA helicase (C10orf2) mRNA, complete cds; nuclear gene for mitochondrial product; alternatively spliced.
AF292005 - Homo sapiens truncated putative T7-like mitochondrial DNA helicase (C10orf2) mRNA, complete cds; nuclear gene for mitochondrial product; alternatively spliced.
BC033762 - Homo sapiens chromosome 10 open reading frame 2, mRNA (cDNA clone MGC:44998 IMAGE:3854007), complete cds.
JD330400 - Sequence 311424 from Patent EP1572962.
JD337007 - Sequence 318031 from Patent EP1572962.
BC013349 - Homo sapiens chromosome 10 open reading frame 2, mRNA (cDNA clone IMAGE:3954451), partial cds.
JD044693 - Sequence 25717 from Patent EP1572962.
DQ586520 - Homo sapiens piRNA piR-53632, complete sequence.
AK025485 - Homo sapiens cDNA: FLJ21832 fis, clone HEP01571.
CU689728 - Synthetic construct Homo sapiens gateway clone IMAGE:100023236 5' read PEO1 mRNA.
KJ902911 - Synthetic construct Homo sapiens clone ccsbBroadEn_12305 C10orf2 gene, encodes complete protein.
KR710836 - Synthetic construct Homo sapiens clone CCSBHm_00017589 C10orf2 (C10orf2) mRNA, encodes complete protein.
KR710837 - Synthetic construct Homo sapiens clone CCSBHm_00017590 C10orf2 (C10orf2) mRNA, encodes complete protein.
KR710838 - Synthetic construct Homo sapiens clone CCSBHm_00017592 C10orf2 (C10orf2) mRNA, encodes complete protein.
KR710839 - Synthetic construct Homo sapiens clone CCSBHm_00017616 C10orf2 (C10orf2) mRNA, encodes complete protein.
DQ593066 - Homo sapiens piRNA piR-33178, complete sequence.
AK022959 - Homo sapiens cDNA FLJ12897 fis, clone NT2RP2004207.
JD445936 - Sequence 426960 from Patent EP1572962.
JD077316 - Sequence 58340 from Patent EP1572962.
JD290962 - Sequence 271986 from Patent EP1572962.
JD280422 - Sequence 261446 from Patent EP1572962.
JD063495 - Sequence 44519 from Patent EP1572962.
JD507116 - Sequence 488140 from Patent EP1572962.
JD514774 - Sequence 495798 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q96RR1 (Reactome details) participates in the following event(s):

R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-1592230 Mitochondrial biogenesis
R-HSA-1852241 Organelle biogenesis and maintenance

-  Other Names for This Gene
  Alternate Gene Symbols: B2CQL2, C10orf2, NM_021830, NP_068602, PEO1, PEO1_HUMAN, Q6MZX2, Q6PJP5, Q96RR0, Q96RR1
UCSC ID: uc001ksf.2
RefSeq Accession: NM_021830
Protein: Q96RR1 (aka PEO1_HUMAN)
CCDS: CCDS7506.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TWNK:
ataxias (Hereditary Ataxia Overview)
perrault (Perrault Syndrome)
sca-io (Infantile-Onset Spinocerebellar Ataxia)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_021830.4
exon count: 5CDS single in 3' UTR: no RNA size: 3640
ORF size: 2055CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3639.00frame shift in genome: no % Coverage: 99.48
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.