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Aliases for TWNK Gene

Aliases for TWNK Gene

  • Twinkle MtDNA Helicase 2 3 5
  • T7 Helicase-Related Protein With Intramitochondrial Nucleoid Localization 2 3
  • T7 Gp4-Like Protein With Intramitochondrial Nucleoid Localization 3 4
  • Progressive External Ophthalmoplegia 1 Protein 3 4
  • T7-Like Mitochondrial DNA Helicase 3 4
  • C10orf2 3 4
  • PEO1 3 4
  • Infantile Onset Spinocerebellar Ataxia (Autosomal Recessive) 2
  • Chromosome 10 Open Reading Frame 2 2
  • Twinkle Protein, Mitochondrial 3
  • Mitochondrial Twinkle Protein 3
  • EC 3.6.4.12 4
  • Ataxin 8 3
  • MTDPS7 3
  • PRLTS5 3
  • SANDO 3
  • ATXN8 3
  • PEOA3 3
  • TWINL 3
  • IOSCA 3
  • SCA8 3
  • PEO 3

External Ids for TWNK Gene

Previous HGNC Symbols for TWNK Gene

  • IOSCA
  • C10orf2

Summaries for TWNK Gene

Entrez Gene Summary for TWNK Gene

  • 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]

GeneCards Summary for TWNK Gene

TWNK (Twinkle MtDNA Helicase) is a Protein Coding gene. Diseases associated with TWNK include Mitochondrial Dna Depletion Syndrome 7 and Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Dominant 3. Among its related pathways are Organelle biogenesis and maintenance and Mitochondrial Gene Expression.

UniProtKB/Swiss-Prot for TWNK Gene

  • 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.

Gene Wiki entry for TWNK Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TWNK Gene

Genomics for TWNK Gene

Regulatory Elements for TWNK Gene

Enhancers for TWNK Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH10F100653 2.5 VISTA Ensembl ENCODE 10.5 -332.7 -332673 2.3 PKNOX1 ZNF133 FEZF1 GLI4 ZNF2 ZNF121 GLIS2 KLF7 ZNF202 ZNF263 EBAG9P1 PHBP9 TWNK SLC25A28 HIF1AN COX15 ENSG00000274660 NDUFB8
GH10F100485 1.6 VISTA ENCODE 11.3 -501.5 -501536 1.5 HDGF PKNOX1 CREB3L1 ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 ZNF143 SEC31B TWNK CHUK LOC105378452 GC10M100500
GH10F100909 1.4 Ensembl ENCODE 11.4 -75.5 -75472 5.0 HDGF PKNOX1 MLX WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 MRPL43 TWNK ENSG00000272572 CHUK SEMA4G MIR608 SLF2 ENSG00000222072
GH10F101030 1.4 FANTOM5 ENCODE 10.7 +45.9 45881 6.4 HDGF ATF1 PKNOX1 ARID4B SIN3A FEZF1 DMAP1 ZNF48 ZNF2 ZNF121 PDZD7 KAZALD1 TLX1 TLX1NB SEMA4G ENSG00000236662 MRPL43 TWNK MIR608 SFXN3
GH10F101828 1.4 FANTOM5 ENCODE 10 +843.6 843617 4.4 HDGF PKNOX1 CREB3L1 ARID4B SIN3A ZNF2 ZNF302 ZNF416 ZNF143 ZNF207 LDB1 PPRC1 GBF1 ENSG00000272572 ARL3 HPS6 SUFU MGEA5 SFXN2 KCNIP2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around TWNK on UCSC Golden Path with GeneCards custom track

Promoters for TWNK Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000222255 33 1601 HDGF PKNOX1 CREB3L1 ARID4B SIN3A DMAP1 ZNF2 SLC30A9 ZNF416 ZNF143

Genomic Location for TWNK Gene

Chromosome:
10
Start:
100,987,367 bp from pter
End:
100,994,403 bp from pter
Size:
7,037 bases
Orientation:
Plus strand

Genomic View for TWNK Gene

Genes around TWNK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TWNK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TWNK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TWNK Gene

Proteins for TWNK Gene

  • Protein details for TWNK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96RR1-PEO1_HUMAN
    Recommended name:
    Twinkle protein, mitochondrial
    Protein Accession:
    Q96RR1
    Secondary Accessions:
    • B2CQL2
    • Q6MZX2
    • Q6PJP5
    • Q96RR0

    Protein attributes for TWNK Gene

    Size:
    684 amino acids
    Molecular mass:
    77154 Da
    Quaternary structure:
    • Forms multimers in vitro, including hexamers. Interacts with POLG in vitro.

    Alternative splice isoforms for TWNK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TWNK Gene

Post-translational modifications for TWNK Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TWNK Gene

No data available for DME Specific Peptides for TWNK Gene

Domains & Families for TWNK Gene

Gene Families for TWNK Gene

Protein Domains for TWNK Gene

Suggested Antigen Peptide Sequences for TWNK Gene

Graphical View of Domain Structure for InterPro Entry

Q96RR1

UniProtKB/Swiss-Prot:

PEO1_HUMAN :
  • Contains 1 SF4 helicase domain.
Domain:
  • Contains 1 SF4 helicase domain.
genes like me logo Genes that share domains with TWNK: view

Function for TWNK Gene

Molecular function for TWNK Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + H(2)O = ADP + phosphate.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for TWNK Gene

Gene Ontology (GO) - Molecular Function for TWNK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 14739292
GO:0003678 DNA helicase activity IEA --
GO:0003697 single-stranded DNA binding IDA 18971204
GO:0004386 helicase activity IEA --
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with TWNK: view
genes like me logo Genes that share phenotypes with TWNK: view

Human Phenotype Ontology for TWNK Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TWNK Gene

MGI Knock Outs for TWNK:

Animal Model Products

Inhibitory RNA Products

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for TWNK Gene

Localization for TWNK Gene

Subcellular locations from UniProtKB/Swiss-Prot for TWNK Gene

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.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TWNK gene
Compartment Confidence
mitochondrion 5
nucleus 2
cytosol 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for TWNK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA --
GO:0005759 mitochondrial matrix TAS --
GO:0042645 mitochondrial nucleoid IEA,IDA 18063578
genes like me logo Genes that share ontologies with TWNK: view

Pathways & Interactions for TWNK Gene

genes like me logo Genes that share pathways with TWNK: view

Gene Ontology (GO) - Biological Process for TWNK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006260 DNA replication IEA --
GO:0006264 mitochondrial DNA replication NAS 12975372
GO:0006268 DNA unwinding involved in DNA replication IEA --
GO:0006390 transcription from mitochondrial promoter IMP 18971204
GO:0007005 mitochondrion organization TAS --
genes like me logo Genes that share ontologies with TWNK: view

No data available for SIGNOR curated interactions for TWNK Gene

Drugs & Compounds for TWNK Gene

(3) Drugs for TWNK Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Water Approved Pharma 0
Adenosine triphosphate Approved Nutra 0

(1) Additional Compounds for TWNK Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with TWNK: view

Transcripts for TWNK Gene

Unigene Clusters for TWNK Gene

Chromosome 10 open reading frame 2:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for TWNK Gene

No ASD Table

Relevant External Links for TWNK Gene

GeneLoc Exon Structure for
TWNK
ECgene alternative splicing isoforms for
TWNK

Expression for TWNK Gene

NURSA nuclear receptor signaling pathways regulating expression of TWNK Gene:

TWNK

SOURCE GeneReport for Unigene cluster for TWNK Gene:

Hs.22678

mRNA Expression by UniProt/SwissProt for TWNK Gene:

Q96RR1-PEO1_HUMAN
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.

Primer Products

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for TWNK Gene

Orthologs for TWNK Gene

This gene was present in the common ancestor of animals.

Orthologs for TWNK Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia C10orf2 35
  • 99 (a)
OneToOne
C10H10orf2 34
  • 98.77 (n)
cow
(Bos Taurus)
Mammalia C26H10ORF2 35
  • 89 (a)
OneToOne
C26H10orf2 34
  • 88.58 (n)
dog
(Canis familiaris)
Mammalia C10orf2 35
  • 88 (a)
OneToOne
C28H10orf2 34
  • 87.96 (n)
mouse
(Mus musculus)
Mammalia Peo1 16 35 34
  • 84.87 (n)
rat
(Rattus norvegicus)
Mammalia Peo1 34
  • 84.41 (n)
oppossum
(Monodelphis domestica)
Mammalia C10orf2 35
  • 74 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 71 (a)
OneToMany
-- 35
  • 71 (a)
OneToMany
-- 35
  • 69 (a)
OneToMany
-- 35
  • 68 (a)
OneToMany
chicken
(Gallus gallus)
Aves PEO1 35 34
  • 67.34 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia C10orf2 35
  • 67 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100491229 34
  • 66.28 (n)
Str.15313 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.34767 34
zebrafish
(Danio rerio)
Actinopterygii C10orf2 35
  • 62 (a)
OneToOne
peo1 34
  • 61.81 (n)
wufi04d09 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010720 34
  • 59.47 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG5924 34 35
  • 50.46 (n)
worm
(Caenorhabditis elegans)
Secernentea F46G11.1 34 35
  • 47.6 (n)
Species where no ortholog for TWNK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TWNK Gene

ENSEMBL:
Gene Tree for TWNK (if available)
TreeFam:
Gene Tree for TWNK (if available)

Paralogs for TWNK Gene

No data available for Paralogs for TWNK Gene

Variants for TWNK Gene

Sequence variations from dbSNP and Humsavar for TWNK Gene

SNP ID Clin Chr 10 pos Sequence Context AA Info Type
rs111033572 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (PEOA3) [MIM:609286], Pathogenic 100,989,823(+) ACTGG(C/G)CTGAC nc-transcript-variant, reference, missense
rs111033573 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (PEOA3) [MIM:609286], Pathogenic 100,989,285(+) GTACC(A/G/T)CCCTG intron-variant, nc-transcript-variant, upstream-variant-2KB, reference, missense, utr-variant-5-prime
rs111033574 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (PEOA3) [MIM:609286], Pathogenic 100,989,822(+) CACTG(A/G/T)GCTGA nc-transcript-variant, reference, missense, stop-gained
rs111033575 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (PEOA3) [MIM:609286], Pathogenic 100,989,154(+) GTCCT(A/G/T)GGAAG intron-variant, nc-transcript-variant, upstream-variant-2KB, reference, missense, stop-gained, utr-variant-5-prime
rs111033576 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (PEOA3) [MIM:609286], Pathogenic 100,989,271(+) TTCTC(C/G)TATTC intron-variant, nc-transcript-variant, upstream-variant-2KB, reference, missense, utr-variant-5-prime

Structural Variations from Database of Genomic Variants (DGV) for TWNK Gene

Variant ID Type Subtype PubMed ID
nsv467443 CNV loss 19166990
nsv517698 CNV loss 19592680
nsv831965 CNV loss 17160897

Variation tolerance for TWNK Gene

Residual Variation Intolerance Score: 7.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.10; 61.13% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TWNK Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TWNK

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TWNK Gene

Disorders for TWNK Gene

MalaCards: The human disease database

(20) MalaCards diseases for TWNK Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search TWNK in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PEO1_HUMAN
  • Mitochondrial DNA depletion syndrome 7 (MTDPS7) [MIM:271245]: 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 neuropathy. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. In some individuals liver dysfunction and multi-organ failure is present. {ECO:0000269 PubMed:16135556, ECO:0000269 PubMed:17722119, ECO:0000269 PubMed:17921179, ECO:0000269 PubMed:19853444, ECO:0000269 PubMed:22353293}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Perrault syndrome 5 (PRLTS5) [MIM:616138]: A form of Perrault syndrome, a sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. {ECO:0000269 PubMed:25355836}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 (PEOA3) [MIM:609286]: A disorder 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. {ECO:0000269 PubMed:11431692, ECO:0000269 PubMed:12163192, ECO:0000269 PubMed:12921794, ECO:0000269 PubMed:15668446, ECO:0000269 PubMed:16639411, ECO:0000269 PubMed:17614277, ECO:0000269 PubMed:18396044, ECO:0000269 PubMed:18575922, ECO:0000269 PubMed:19353676, ECO:0000269 PubMed:19428252, ECO:0000269 PubMed:20479361, ECO:0000269 PubMed:20880070}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for TWNK

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TWNK
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TWNK
genes like me logo Genes that share disorders with TWNK: view

No data available for Genatlas for TWNK Gene

Publications for TWNK Gene

  1. Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. (PMID: 16135556) Nikali K. … Peltonen L. (Hum. Mol. Genet. 2005) 2 3 4 22 64
  2. The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO. (PMID: 20479361) Fratter C. … Taylor R.W. (Neurology 2010) 3 4 22 64
  3. Molecular analysis in a family presenting with a mild form of late- onset autosomal dominant chronic progressive external ophthalmoplegia. (PMID: 19428252) Negro R. … Petruzzella V. (Neuromuscul. Disord. 2009) 3 4 22 64
  4. Phenotype and clinical course in a family with a new de novo Twinkle gene mutation. (PMID: 18396044) Jeppesen T.D. … Vissing J. (Neuromuscul. Disord. 2008) 3 4 22 64
  5. Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia. (PMID: 18575922) Virgilio R. … Comi G.P. (J. Neurol. 2008) 3 4 22 64

Products for TWNK Gene

Sources for TWNK Gene

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