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

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	56652
Gene name	Twinkle mtDNA helicase
Gene symbol	TWNK
Synonyms (NCBI Gene)	ATXN8C10orf2IOSCAMTDPS7PEOPEO1PEOA3PRLTS5SANDOSCA8TWINL
Chromosome	10
Chromosome location	10q24.31
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

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

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

497

Show/Hide Causal Diseases (14)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Auditory neuropathy	Likely pathogenic	rs756073260, rs757583061	RCV003484478 RCV003484485
Infantile onset spinocerebellar ataxia	Pathogenic; Likely pathogenic	rs2493642676, rs111033574, rs28937887, rs80356544, rs80356540, rs80356542, rs533720034, rs863223919, rs886037832, rs1564808324, rs1590020571, rs779142717, rs781016340, rs1366090807	RCV002287306 RCV002496262 RCV001542762 RCV000004889 RCV000020865 RCV000020866 RCV005412435 RCV004579540 RCV000240394 RCV005231310 RCV000790907 RCV000855767 RCV000855762 RCV000855765
Mitochondrial disease	Likely pathogenic; Pathogenic	rs757068910, rs111033573, rs111033577, rs28937887, rs1554887097, rs1554887213, rs1554887222	RCV003389267 RCV000508874 RCV000508905 RCV000508769 RCV000508920 RCV000508722 RCV000508820
mitochondrial hepatopathy	Likely pathogenic	rs1590018153, rs1451037596	RCV000855766 RCV000855768
Perrault syndrome	Pathogenic	rs672601360, rs672601361	RCV002514865 RCV002516007
Perrault syndrome 5	Pathogenic; Likely pathogenic	rs672601360, rs672601361, rs111033574	RCV000149471 RCV000149472 RCV002496262
Possible mitochondrial disorder - nuclear genes	Pathogenic	rs111033576	RCV006436378
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1	Pathogenic	rs111033574	RCV000855769
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3	Likely pathogenic; Pathogenic	rs1159929268, rs2133939892, rs2493633263, rs111033572, rs111033573, rs111033574, rs111033575, rs111033576, rs111033577, rs28937887, rs111033579, rs80356543, rs267606682, rs757838397, rs1554887097 View all (3 more)	RCV004785286 RCV002250853 RCV000004879 RCV000004880 RCV000004881 RCV000004882 RCV000004883 RCV000004884 RCV000004885 RCV002288465 RCV000004887 RCV000004888 RCV000004892 RCV003123518 RCV004689760 RCV004787794 RCV000779014 RCV001253009
Progressive external ophthalmoplegia with mitochondrial DNA deletions, digenic	Likely pathogenic; Pathogenic	rs28937887	RCV000004886
See cases	Pathogenic; Likely pathogenic	rs80356542, rs776533804	RCV002251876 RCV001199239
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Likely pathogenic; Pathogenic	rs111033574, rs80356543	RCV002496262 RCV000020867
Third degree atrioventricular block	Pathogenic	rs1253531908	RCV002305647
TWNK-related disorder	Likely pathogenic	rs2493626854	RCV003314226

Show/Hide Unknown Diseases (10)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Ataxia Neuropathy Spectrum Disorders	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	rs369223258, rs146265037, rs886046629, rs886046630, rs370783985, rs886046640	RCV000352301 RCV000275226 RCV000342541 RCV000378949 RCV000274766 RCV000364410
Autosomal recessive cerebellar ataxia	Conflicting classifications of pathogenicity; Benign; Uncertain significance; Likely benign	rs11542130, rs17113613, rs3740485, rs3740486, rs3740484, rs201795189, rs556445621, rs863223921, rs116046810, rs370814108, rs182559752, rs369223258, rs145068570, rs148234280, rs187213541 View all (60 more)	RCV000395926 RCV001104761 RCV000328346 RCV000343097 RCV000361730 RCV000396649 RCV000345001 RCV001105895 RCV000402465 RCV000322888 RCV000374204 RCV000406261 RCV001107965 RCV000386725 RCV000336415 RCV000394946 RCV000313818 RCV000263602 RCV000380816 RCV000322115 RCV000268162 RCV000296339 RCV000395193 RCV000359977 RCV000296618 RCV000384190 RCV000391253 RCV000346808 RCV000395716 RCV000317524 RCV000320279 RCV000402616 RCV000333249 RCV000336669 RCV000311980 RCV000353789 RCV000405350 RCV000327796 RCV000281131 RCV000404345 RCV000390735 RCV000356122 RCV000369355 RCV000268971 RCV000378586 RCV000279376 RCV000365196 RCV000371309 RCV000365721 RCV000338309 RCV000368599 RCV000267467 RCV001105998 RCV001107308 RCV001108147 RCV001102533 RCV001104459 RCV001107224 RCV001102633 RCV001102636 RCV001104650 RCV001108045 RCV001108047 RCV001102926 RCV001105996 RCV001103037 RCV001104942 RCV001104944 RCV001103136 RCV001105045 RCV001105050 RCV001108409 RCV001105149 RCV001106279 RCV001105239
Cholangiocarcinoma	Likely benign	rs2863096	RCV005915059
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	rs145068570	RCV005895462
Familial cancer of breast	Conflicting classifications of pathogenicity	rs201795189	RCV005890590
Hereditary spastic paraplegia	Conflicting classifications of pathogenicity; Uncertain significance; Benign; Likely benign	rs142978552, rs755985090, rs1198520632, rs770345181, rs765275995, rs2133942190, rs2133942468, rs868535097, rs1339977334, rs1851660058, rs11542130, rs17113613, rs182559752, rs369223258, rs145068570 View all (5 more)	RCV001847301 RCV001847332 RCV001848349 RCV001848350 RCV001848351 RCV001848352 RCV001848353 RCV001848355 RCV001848356 RCV001848357 RCV001847741 RCV001847742 RCV001847877 RCV001848044 RCV001848043 RCV001848047 RCV001848070 RCV001848071 RCV001848766 RCV001847114
Mitochondrial DNA depletion syndrome	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	rs369223258, rs146265037, rs886046629, rs886046630, rs370783985, rs886046640	RCV000312773 RCV000367436 RCV000288718 RCV000264619 RCV000333328 RCV000307286
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity	rs201795189	RCV005890591
Progressive external ophthalmoplegia with mitochondrial DNA deletions	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	rs369223258, rs146265037, rs886046629, rs886046630, rs370783985, rs886046640	RCV000278667 RCV000309025 RCV000345897 RCV000357427 RCV000329810 RCV000405295
Thymoma	Conflicting classifications of pathogenicity	rs143938897	RCV005893486

Show/Hide Text Mining Associations (48)

Disease Name	Relationship Type	References
Associations from Text MiningDisease 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)