TWNK twinkle mtDNA helicase [Homo sapiens (human)] - Gene

Summary

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

Location:: 10q24.31

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (100987543..100994403)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (101870918..101877778)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (102747300..102754160)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A homozygous mutation of TWNK identified in premature ovarian insufficiency warns of late-onset perrault syndrome.
Title: A homozygous mutation of TWNK identified in premature ovarian insufficiency warns of late-onset perrault syndrome.
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.
Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
Title: Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
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.
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.
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.
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.
Consequences of compromised mitochondrial genome integrity.
Title: Consequences of compromised mitochondrial genome integrity.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (62)

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

Associated conditions

Description	Tests
Infantile onset spinocerebellar ataxia MedGen: C1849096 OMIM: 271245 GeneReviews: Mitochondrial DNA Maintenance Defects Overview	not available
Perrault syndrome 5 MedGen: C4015307 OMIM: 616138 GeneReviews: Perrault Syndrome	not available
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 MedGen: C1836439 OMIM: 609286 GeneReviews: Mitochondrial DNA Maintenance Defects Overview	not available
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis MedGen: C1843851 OMIM: 607459 GeneReviews: POLG-Related Disorders	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-32265 (e-PCR)
- UniSTS:72705

D10S1265 (e-PCR), detects polymorphism
- UniSTS:66307

A004R30 (e-PCR)
- UniSTS:74768

D10S192 (e-PCR)
- UniSTS:77128

STS-W80406 (e-PCR)
- UniSTS:74918

STS-D11794 (e-PCR)
- UniSTS:50393

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 ATP-dependent H2AZ histone chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent H3-H4 histone complex chaperone activity	IEA Inferred from Electronic Annotation more info
enables DNA clamp loader activity	IEA Inferred from Electronic Annotation more info
enables DNA helicase activity	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin extrusion motor activity	IEA Inferred from Electronic Annotation more info
enables cohesin loader activity	IEA Inferred from Electronic Annotation more info
enables double-stranded DNA helicase activity	IEA Inferred from Electronic Annotation more info
enables forked DNA-dependent helicase activity	IEA Inferred from Electronic Annotation more info
enables four-way junction helicase activity	IEA Inferred from Electronic Annotation 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 protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded 3'-5' DNA helicase activity	IEA Inferred from Electronic Annotation more info
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 chromatin looping	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	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
is_active_in mitochondrial chromosome	IDA Inferred from Direct Assay more info	PubMed
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
located_in mitochondrion	HTP 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

EC 5.6.2.3

NP_001157285.1

EC 5.6.2.3

NP_001157286.1

EC 5.6.2.3

NP_001355204.1

EC 5.6.2.3

NP_068602.2

EC 5.6.2.3

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

NG_012624.1 RefSeqGene

Range

5008..11868

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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
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

NR_160738.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL133215

Related

ENST00000643860.1
NR_160739.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL133215
NR_160740.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL133215
NR_160741.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL133215
NR_160742.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL133215