Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID Entrez Gene ID - the GENE ID in NCBI Gene database.	56652
Gene name Gene Name - the full gene name approved by the HGNC.	Twinkle mtDNA helicase
Gene symbol Gene Symbol - the official gene symbol approved by the HGNC.	TWNK
Synonyms (NCBI Gene) Gene synonyms aliases	ATXN8, C10orf2, IOSCA, MTDPS7, PEO, PEO1, PEOA3, PRLTS5, SANDO, SCA8, TWINL
Chromosome Chromosome number	10
Chromosome location Chromosomal Location - indicates the cytogenetic location of the gene or region on the chromosome.	10q24.31
Summary Summary of gene provided in NCBI Entrez 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

Show/Hide all(21)

SNP ID	Visualize variation	Clinical significance	Consequence
rs80356540	A>G	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs80356541	C>T	Pathogenic	Intron variant, synonymous variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant
rs80356544	C>T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs111033572	G>C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs111033574	G>A,C,T	Pathogenic	Stop gained, missense variant, non coding transcript variant, coding sequence variant
rs182559752	G>A,C,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant, non coding transcript variant, 3 prime UTR variant
rs369588002	G>A	Uncertain-significance, pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs386834145	C>G	Likely-pathogenic, uncertain-significance	Coding sequence variant, non coding transcript variant, missense variant
rs386834146	C>G,T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs672601360	A>G	Pathogenic	3 prime UTR variant, missense variant, non coding transcript variant, coding sequence variant
rs672601361	T>G	Pathogenic	Coding sequence variant, 5 prime UTR variant, non coding transcript variant, missense variant
rs753386843	G>A	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs773918715	C>G,T	Likely-pathogenic	Synonymous variant, intron variant, 5 prime UTR variant, missense variant, coding sequence variant, non coding transcript variant
rs863223925	TT>-,TTT	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1064797150	C>T	Likely-pathogenic	3 prime UTR variant, non coding transcript variant, stop gained, coding sequence variant
rs1085307937	G>A	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1366090807	C>G,T	Likely-pathogenic	Synonymous variant, 5 prime UTR variant, non coding transcript variant, missense variant, coding sequence variant
rs1554887207	T>C	Likely-pathogenic	Initiator codon variant, missense variant, coding sequence variant, non coding transcript variant
rs1554887213	G>T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1554887222	T>C	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs1590020571	C>G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant

Show/Hide all(9)

miRTarBase ID	miRNA	Experiments	Reference
MIRT528625	hsa-miR-4747-3p	PAR-CLIP	22012620
MIRT528624	hsa-miR-4717-3p	PAR-CLIP	22012620
MIRT528623	hsa-miR-4267	PAR-CLIP	22012620
MIRT528622	hsa-miR-6741-3p	PAR-CLIP	22012620
MIRT528621	hsa-miR-4638-5p	PAR-CLIP	22012620
MIRT528620	hsa-miR-4290	PAR-CLIP	22012620
MIRT528619	hsa-miR-874-5p	PAR-CLIP	22012620
MIRT528618	hsa-miR-5704	PAR-CLIP	22012620
MIRT528617	hsa-miR-1295a	PAR-CLIP	22012620

Show/Hide all(37)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0000262	Component	Mitochondrial chromosome	IDA	26253742
GO:0002020	Function	Protease binding	IPI	14739292
GO:0003678	Function	DNA helicase activity	IBA
GO:0003678	Function	DNA helicase activity	IEA
GO:0003697	Function	Single-stranded DNA binding	IBA
GO:0003697	Function	Single-stranded DNA binding	IDA	18971204
GO:0003697	Function	Single-stranded DNA binding	IEA
GO:0004386	Function	Helicase activity	IEA
GO:0005515	Function	Protein binding	IPI	28514442, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006260	Process	DNA replication	IEA
GO:0006260	Process	DNA replication	IEA
GO:0006261	Process	DNA-templated DNA replication	IDA	15167897
GO:0006264	Process	Mitochondrial DNA replication	IBA
GO:0006264	Process	Mitochondrial DNA replication	IEA
GO:0006264	Process	Mitochondrial DNA replication	IMP	18971204
GO:0006264	Process	Mitochondrial DNA replication	NAS	12975372
GO:0006390	Process	Mitochondrial transcription	IMP	18971204
GO:0008289	Function	Lipid binding	IDA	34950192
GO:0008289	Function	Lipid binding	IEA
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016853	Function	Isomerase activity	IEA
GO:0016887	Function	ATP hydrolysis activity	IDA	34950192
GO:0016887	Function	ATP hydrolysis activity	IEA
GO:0034214	Process	Protein hexamerization	IDA	18971204
GO:0042645	Component	Mitochondrial nucleoid	IDA	18063578, 18971204, 23275553
GO:0042645	Component	Mitochondrial nucleoid	IEA
GO:0042802	Function	Identical protein binding	IPI	18971204
GO:0043139	Function	5'-3' DNA helicase activity	IDA	12975372, 15167897, 18971204, 34950192
GO:0043139	Function	5'-3' DNA helicase activity	IEA

MIM	HGNC	e!Ensembl
606075	1160	ENSG00000107815

Protein

UniProt ID

Q96RR1

Protein name

Twinkle mtDNA helicase (EC 5.6.2.3) (Progressive external ophthalmoplegia 1 protein) (T7 gp4-like protein with intramitochondrial nucleoid localization) (T7-like mitochondrial DNA helicase) (Twinkle protein, mitochondrial)

Protein function

[Isoform 1]: Mitochondrial helicase involved in mtDNA replication and repair (PubMed:12975372, PubMed:15167897, PubMed:17324440, PubMed:18039713, PubMed:18971204, PubMed:25824949, PubMed:26887820, PubMed:27226550). Might have a role in mtDNA rep

PDB

7T8B , 7T8C

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF13481	AAA_25	374 → 564		Domain

Tissue specificity

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 coregula

Sequence

MWVLLRSGYPLRILLPLRGEWMGRRGLPRNLAPGPPRRRYRKETLQALDMPVLPVTATEI
RQYLRGHGIPFQDGHSCLRALSPFAESSQLKGQTGVTTSFSLFIDKTTGHFLCMTSLAEG
SWEDFQASVEGRGDGAREGFLLSKAPEFEDSEEVRRIWNRAIPLWELPDQEEVQLADTMF
GLTKVTDDTLKRFSVRYLRPARSLVFPWFSPGGSGLRGLKLLEAKCQGDGVSYEETTIPR
PSAYHNLFGLPLISRRDAEVVLTSRELDSLALNQSTGLPTLTLPRGTTCLPPALLPYLEQ
FRRIVFWLGDDLRSWEAAKLFARKLNPKRCFLVRPGDQQPRPLEALNGGFNLSRILRTAL
PAWHKSIVSFRQLREEVLGELSNVEQAAGLRWSRFPDLNRILKGHRKGELTVFTGPTGSG
KTTFISEYALDLCSQGVNTLWGSFEISNVRLARVMLTQFAEGRLEDQLDKYDHWADRFED
LPLYFMTFHGQQSIRTVIDTMQHAVYVYDICHVIIDNLQFMMGHEQLSTDRIAAQDYIIG
VFRKFATDNNCHVTLVIHPRKEDDDKELQTASIFGSAKASQEADNVLILQDRKLVTGPGK
RYLQVSKNRFDGDVGVFPLEFNKNSLTFSIPPKNKARLKKIKDDTGPVAKKPSSGKKGAT
TQNSEICSGQAPTPDQPDTSKRSK

Sequence length

684

Interactions

View interactions

	KEGG		Reactome
	Spinocerebellar ataxia		Transcriptional activation of mitochondrial biogenesis

Show/Hide Causal Diseases (4)

Disease merge term	Disease name	dbSNP ID	References
Causal Diseases caused by PATHOGENIC or LIKELY PATHOGENIC variants from ClinVar only
Ataxia neuropathy spectrum disorder	sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	rs80356543	N/A
Fatal Mitochondrial Disease	Mitochondrial disease	rs111033577, rs28937887, rs1554887097, rs1554887213, rs111033573, rs1554887222	N/A
progressive external ophthalmoplegia with mitochondrial dna deletions	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3	rs111033574, rs28937887, rs1554887097, rs111033572, rs111033579, rs111033573, rs80356543, rs1554887213, rs111033575, rs758026634, rs111033576, rs267606682, rs111033577	N/A
Spinocerebellar Ataxia	infantile onset spinocerebellar ataxia	rs779142717, rs863223919, rs781016340, rs886037832, rs1366090807, rs28937887, rs80356544, rs1564808324, rs80356540, rs1590020571, rs80356542	N/A

Show/Hide Unknown Diseases (7)

Disease merge term	Disease name	Evidence	References	Source
Unknown Includes: (1) ClinVar NON-pathogenic variants (Uncertain, Benign, Conflicting, VUS), (2) GenCC associations, (3) GWAS associations, (4) CBGDA evidence-based associations. NOTE: Diseases with pathogenic evidence are excluded to avoid conflicts.
Cerebellar Ataxia	Autosomal recessive cerebellar ataxia	N/A	N/A	ClinVar
External ophthalmoplegia	autosomal dominant progressive external ophthalmoplegia	N/A	N/A	GenCC
Hereditary spastic paraplegia	Hereditary spastic paraplegia	N/A	N/A	ClinVar
Mitochondrial DNA Deletion Syndrome	mitochondrial DNA depletion syndrome 7 (hepatocerebral type)	N/A	N/A	GenCC
mitochondrial dna depletion syndrome	Mitochondrial DNA depletion syndrome	N/A	N/A	ClinVar
Mitochondrial DNA Depletion Syndrome, hepatocerebral	mitochondrial DNA depletion syndrome, hepatocerebrorenal form	N/A	N/A	GenCC
Perrault Syndrome	Perrault syndrome	N/A	N/A	GenCC

Show/Hide Text Mining Associations (48)

Disease Name	Relationship Type	References
Associations from Text Mining Disease associations identified through Pubtator
Alcoholic Neuropathy	Associate	24816431
Ataxia	Associate	31852434, 37932750
Atrophy	Associate	28178980
Auditory neuropathy	Associate	39340975
Brain Stem Neoplasms	Associate	37316776
Carcinoma Ovarian Epithelial	Associate	22233925
Cerebellar Ataxia	Associate	32234020
Deafness	Associate	32234020, 33095980
Depressive Disorder	Associate	31852434
Disease	Associate	25355836
Genetic Diseases Inborn	Associate	27226550, 28178980, 31455392, 31600844
Gonadal Disorders	Associate	31852434
Gonadal Dysgenesis	Associate	31852434
Gonadal Dysgenesis 46 XX	Associate	39529088
Gonadal dysgenesis XX type deafness	Associate	25355836, 28178980, 31455392, 31852434, 32234020, 37932750, 38295749, 39340975
Hearing Disorders	Associate	39684270
Hearing Loss	Associate	28178980, 31852434
Hepatic Encephalopathy	Associate	20659899, 31455392
Hypesthesia	Associate	32234020
Intellectual Disability	Associate	24816431
Kearns Sayre Syndrome	Associate	33396418
MERRF Syndrome	Associate	21689831
Mitochondrial Diseases	Associate	20659899
Mitochondrial Encephalomyopathies	Associate	33396418
Mitochondrial Myopathy with a Defect in Mitochondrial Protein Transport	Associate	27226550
Muscle Weakness	Associate	31852434
Muscular Diseases	Associate	24816431
Myasthenia Gravis	Associate	24014582
Myasthenic Syndromes Congenital	Associate	24014582
Nerve Degeneration	Associate	24816431
Ophthalmoplegia	Associate	20659899, 21689831, 24018892
Ophthalmoplegia Chronic Progressive External	Associate	18195150, 21301859, 21689831, 24014582, 24018892, 24086434, 32234020, 37316776
Ovarian Neoplasms	Associate	1586592, 19654294, 27465688, 38114660
Paraparesis Spastic	Associate	31852434
Parkinson Disease	Associate	19788048, 35792653
Parkinson Disease Secondary	Associate	21301859, 35792653
Peripheral Nervous System Diseases	Associate	24816431, 32234020
Polyneuropathies	Associate	24816431, 31852434
Pre Eclampsia	Associate	27788142
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions Autosomal Dominant 1	Associate	18989381, 20479361, 24018892, 31600844, 35792653
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions Autosomal Dominant 3	Associate	25355836
Ptosis Hereditary Congenital 2	Associate	21689831, 24018892, 35792653
Sensorimotor neuropathy with ataxia autosomal dominant	Associate	37932750
Sensory ataxic neuropathy dysarthria and ophthalmoparesis	Associate	33396418
Spinocerebellar Ataxias	Associate	20659899, 24816431
Vestibulocochlear Nerve Diseases	Associate	28178980
Visceral myopathy familial external ophthalmoplegia	Associate	19667227, 20659899, 31455269, 36311265
Wallerian degeneration of the pyramidal tract	Associate	31852434

TWNK (twinkle mtDNA helicase)