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    TWNK twinkle mtDNA helicase [ Homo sapiens (human) ]

    Gene ID: 56652, updated on 5-Mar-2024

    Summary

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    Official Symbol
    TWNKprovided by HGNC
    Official Full Name
    twinkle mtDNA helicaseprovided by HGNC
    Primary source
    HGNC:HGNC:1160
    See related
    Ensembl:ENSG00000107815 MIM:606075; AllianceGenome:HGNC:1160
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PEO; PEO1; SCA8; ATXN8; IOSCA; PEOA3; SANDO; TWINL; MTDPS7; PRLTS5; C10orf2
    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]
    Expression
    Ubiquitous expression in testis (RPKM 6.0), lymph node (RPKM 3.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    10q24.31
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (100987543..100994403)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (101870918..101877778)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (102747300..102754160)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene semaphorin 4G Neighboring gene microRNA 608 Neighboring gene mitochondrial ribosomal protein L43 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3902 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:102755784-102756653 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2712 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2713 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2714 Neighboring gene leucine zipper tumor suppressor 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:102768034-102768715 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:102768716-102769396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3904 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3905 Neighboring gene PDZ domain containing 7 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3906 Neighboring gene sideroflexin 3

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ. Johnson LC, et al. J Biol Chem, 2023 Jan. PMID 36528058, Free PMC Article
    2. Structural insight and characterization of human Twinkle helicase in mitochondrial disease. Riccio AA, et al. Proc Natl Acad Sci U S A, 2022 Aug 9. PMID 35914129, Free PMC Article
    3. Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation. Zhu GY, et al. Clin Neurophysiol, 2020 Jul. PMID 32387964
    4. Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase. Kaur P, et al. J Biol Chem, 2020 Apr 24. PMID 32213598, Free PMC Article
    5. Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders. Domínguez-Ruiz M, et al. J Transl Med, 2019 Aug 28. PMID 31455392, Free PMC Article

    See all (126) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase gamma.
      Title: The N-terminal domain of human mitochondrial helicase Twinkle has DNA-binding activity crucial for supporting processive DNA synthesis by polymerase γ.
    2. Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
      Title: Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
    3. Progressive External Ophthalmoplegia in Polish Patients-From Clinical Evaluation to Genetic Confirmation.
      Title: Progressive External Ophthalmoplegia in Polish Patients-From Clinical Evaluation to Genetic Confirmation.
    4. Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia.
      Title: Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia.
    5. Stimulation of Variant Forms of the Mitochondrial DNA Helicase Twinkle by the Mitochondrial Single-Stranded DNA-Binding Protein.
      Title: Stimulation of Variant Forms of the Mitochondrial DNA Helicase Twinkle by the Mitochondrial Single-Stranded DNA-Binding Protein.
    6. Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation.
      Title: Characteristics of globus pallidus internus local field potentials in generalized dystonia patients with TWNK mutation.
    7. Consequences of compromised mitochondrial genome integrity.
      Title: Consequences of compromised mitochondrial genome integrity.
    8. Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase.
      Title: Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase.
    9. patients with Perrault syndrome caused by TWNK mutations will manifest neurological signs in adulthood.
      Title: Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders.
    10. Two novel TWNK c.1186 C > T/ c.1844 G > C compound heterozygous mutations which were probably the disease-causing mutations of hepatocerebral form of Mitochondrial DNA depletion syndrome (MDS) and described the clinical manifestations of the proband, which expanded the phenotypic spectrum of MDS caused by variants in TWNK.
      Title: Whole exome sequencing reveals two novel compound heterozygous mutations in TWNK as a cause of the hepatocerebral form of mitochondrial DNA depletion syndrome: a case report.
    Submit: New GeneRIF Correction See all GeneRIFs (61)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ21832

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 5'-3' DNA helicase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP hydrolysis activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA helicase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables isomerase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables lipid binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protease binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables single-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables single-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA unwinding involved in DNA replication IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to glucose stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitochondrial DNA replication IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrial DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrial DNA replication NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in mitochondrial transcription IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein hexamerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in mitochondrial inner membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial nucleoid IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    twinkle mtDNA helicase
    Names
    T7 gp4-like protein with intramitochondrial nucleoid localization
    T7 helicase-related protein with intramitochondrial nucleoid localization
    T7-like mitochondrial DNA helicase
    ataxin 8
    progressive external ophthalmoplegia 1 protein
    twinkle protein, mitochondrial
    NP_001157284.1
    NP_001157285.1
    NP_001157286.1
    NP_001355204.1
    NP_068602.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012624.1 RefSeqGene

      Range
      5008..11868
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001163812.2 → NP_001157284.1  twinkle mtDNA helicase isoform B

      See identical proteins and their annotated locations for NP_001157284.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region which introduces a novel stop codon, compared to variant 1. The encoded protein (isoform B; also known as Twinky) has a shorter and distinct C-terminus, which lacks a C-terminal domain required for hexamer formation, compared to isoform A.
      Source sequence(s)
      AF292005, AK025485, AL133215, BC013349, DB090322
      Consensus CDS
      CCDS53570.1
      UniProtKB/Swiss-Prot
      Q96RR1
      UniProtKB/TrEMBL
      Q9H6V3
      Related
      ENSP00000359248.1, ENST00000370228.2
      Conserved Domains (2) summary
      cd01029
      Location:259 → 335
      TOPRIM_primases; TOPRIM_primases: The topoisomerase-primase (TORPIM) nucleotidyl transferase/hydrolase domain found in the active site regions of bacterial DnaG-type primases and their homologs. Primases synthesize RNA primers for the initiation of DNA replication. DnaG ...
      cl21455
      Location:374 → 580
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    2. NM_001163813.2 → NP_001157285.1  twinkle mtDNA helicase isoform C

      See identical proteins and their annotated locations for NP_001157285.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in exon 1 that results in the use of an in-frame downstream start codon, compared to variant 1. The encoded protein (isoform C) lacks most of the N-terminus, which contains a mitochondrial targeting sequence and probable ssDNA binding domain, compared to isoform A.
      Source sequence(s)
      AK025485, AL133215, BQ643363, CB112401
      Consensus CDS
      CCDS86136.1
      UniProtKB/TrEMBL
      A0A2R8Y4V4, B4DLM7
      Related
      ENSP00000494326.1, ENST00000473656.5
      Conserved Domains (1) summary
      cd01122
      Location:1 → 175
      Twinkle_C; C-terminal domain of Twinkle

    3. NM_001163814.2 → NP_001157286.1  twinkle mtDNA helicase isoform D

      See identical proteins and their annotated locations for NP_001157286.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has multiple splice site differences, compared to variant 1. The encoded protein (isoform D) lacks most of the N-terminus, which contains a mitochondrial targeting sequence and probable ssDNA binding domain, and has a shorter and distinct C-terminus, which lacks a C-terminal domain required for hexamer formation, compared to isoform A.
      Source sequence(s)
      AK025485, AL133215, CB112401
      Consensus CDS
      CCDS86137.1
      UniProtKB/TrEMBL
      A0A2R8Y746
      Related
      ENSP00000496012.1, ENST00000476766.5
      Conserved Domains (1) summary
      cl38936
      Location:1 → 126
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    4. NM_001368275.1 → NP_001355204.1  twinkle mtDNA helicase isoform C

      Status: REVIEWED

      Source sequence(s)
      AL133215
      Consensus CDS
      CCDS86136.1
      UniProtKB/TrEMBL
      A0A2R8Y4V4, B4DLM7
      Conserved Domains (1) summary
      cd01122
      Location:1 → 175
      Twinkle_C; C-terminal domain of Twinkle

    5. NM_021830.5 → NP_068602.2  twinkle mtDNA helicase isoform A

      See identical proteins and their annotated locations for NP_068602.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (A; also known as Twinkle).
      Source sequence(s)
      AF292004, AK025485, AL133215, DB090322
      Consensus CDS
      CCDS7506.1
      UniProtKB/Swiss-Prot
      B2CQL2, Q6MZX2, Q6PJP5, Q96RR0, Q96RR1
      UniProtKB/TrEMBL
      E5KSY5
      Related
      ENSP00000309595.2, ENST00000311916.8
      Conserved Domains (2) summary
      cd01029
      Location:259 → 335
      TOPRIM_primases; TOPRIM_primases: The topoisomerase-primase (TORPIM) nucleotidyl transferase/hydrolase domain found in the active site regions of bacterial DnaG-type primases and their homologs. Primases synthesize RNA primers for the initiation of DNA replication. DnaG ...
      cd01122
      Location:374 → 632
      GP4d_helicase; GP4d_helicase is a homohexameric 5'-3' helicases. Helicases couple NTP hydrolysis to the unwinding of nucleic acid duplexes into their component strands.

    RNA

    1. NR_160738.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL133215
      Related
      ENST00000643860.1

    2. NR_160739.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL133215

    3. NR_160740.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL133215

    4. NR_160741.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL133215

    5. NR_160742.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL133215

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      100987543..100994403
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      101870918..101877778
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96RR1.1 GenPept UniProtKB/Swiss-Prot:Q96RR1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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