TWNK (twinkle mtDNA helicase)

Gene

• Entrez ID: 56652
• Gene name: Twinkle mtDNA helicase
• Gene symbol: TWNK
• Synonyms (NCBI Gene): ATXN8, C10orf2, IOSCA, MTDPS7, PEO, PEO1, PEOA3, PRLTS5, SANDO, SCA8, TWINL
• 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

SNPs

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

miRNA

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

Gene ontology (GO)

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

Other IDs

• MIM: 606075
• HGNC: 1160
• e!Ensembl: 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

Pathways

KEGG:

Spinocerebellar ataxia

Reactome:

Transcriptional activation of mitochondrial biogenesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Auditory neuropathy	Likely pathogenic	rs756073260, rs757583061	RCV003484478 RCV003484485	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
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	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Mitochondrial disease	Likely pathogenic; Pathogenic	rs757068910, rs111033573, rs111033577, rs28937887, rs1554887097, rs1554887213, rs1554887222	RCV003389267 RCV000508874 RCV000508905 RCV000508769 RCV000508920 RCV000508722 RCV000508820	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
mitochondrial hepatopathy	Likely pathogenic	rs1590018153, rs1451037596	RCV000855766 RCV000855768	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Perrault syndrome	Pathogenic	rs672601360, rs672601361	RCV002514865 RCV002516007	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Perrault syndrome 5	Pathogenic; Likely pathogenic	rs672601360, rs672601361, rs111033574	RCV000149471 RCV000149472 RCV002496262	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Possible mitochondrial disorder - nuclear genes	Pathogenic	rs111033576	RCV006436378	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1	Pathogenic	rs111033574	RCV000855769	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
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, rs1554887213, rs758026634, rs1382829987	RCV004785286 RCV002250853 RCV000004879 RCV000004880 RCV000004881 RCV000004882 RCV000004883 RCV000004884 RCV000004885 RCV002288465 RCV000004887 RCV000004888 RCV000004892 RCV003123518 RCV004689760 RCV004787794 RCV000779014 RCV001253009	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Progressive external ophthalmoplegia with mitochondrial DNA deletions, digenic	Likely pathogenic; Pathogenic	rs28937887	RCV000004886	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Likely pathogenic; Pathogenic	rs111033574, rs80356543	RCV002496262 RCV000020867	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Third degree atrioventricular block	Pathogenic	rs1253531908	RCV002305647	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
TWNK-related disorder	Likely pathogenic	rs2493626854	RCV003314226	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Ataxia Neuropathy Spectrum Disorders	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal recessive cerebellar ataxia	Conflicting classifications of pathogenicity; Benign; Uncertain significance; Likely benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
BILATERAL PTOSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMPLETE ATRIOVENTRICULAR BLOCK	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPLETION OF MITOCHONDRIAL DEOXYRIBONUCLEIC ACID	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DYSPHONIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GONADAL DYSGENESIS XX TYPE DEAFNESS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary spastic paraplegia	Conflicting classifications of pathogenicity; Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial DNA depletion syndrome	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DNA DEPLETION SYNDROME 7	—	CTD, GWAS catalog, HPO CTD, GWAS catalog, HPO CTD, GWAS catalog, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DNA DEPLETION SYNDROME HEPATOCEREBRORENAL FORM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DNA DEPLETION SYNDROME, HEPATOCEREBRORENAL FORM	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERRAULT SYNDROME 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERRAULT SYNDROME 3	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERRAULT SYNDROME 4	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERRAULT SYNDROME TYPE 1	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERRAULT SYNDROME TYPE 2	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive external ophthalmoplegia with mitochondrial DNA deletions	Conflicting classifications of pathogenicity; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORY ATAXIC NEUROPATHY-DYSARTHRIA-OPHTHALMOPARESIS SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
XX GONADAL DYSGENESIS-DEAFNESS SYNDROME-PROGRESSIVE NEUROLOGICAL MANIFESTATIONS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alpers Syndrome (disorder)	Alpers Syndrome	BEFREE	22459315		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	31852434, 37932750	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia, Spinocerebellar	Spinocerebellar Ataxia	BEFREE	10712199, 10813808, 12431257, 14756671, 15080863, 26077168, 29316893		★☆☆☆☆ Found in Text Mining only
Ataxia, Spinocerebellar	Spinocerebellar Ataxia	LHGDN	12545428, 16135556, 17132942		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrophy	Atrophy	Pubtator	28178980	Associate	★☆☆☆☆ Found in Text Mining only
Atrophy/Degeneration affecting the brainstem	Brainstem Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Auditory neuropathy	Auditory Neuropathy	CLINVAR_DG	27551684		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Auditory neuropathy	Auditory neuropathy	Pubtator	39340975	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Autosomal dominant progressive external ophthalmoplegia	External ophthalmoplegia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	BEFREE	24018892, 24061067		★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brain Stem Neoplasms	Brain stem neoplasms	Pubtator	37316776	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	22233925	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	19654294, 21385444, 24895135, 25684390, 25817828, 27935869, 29410730		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	15258213		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Ataxia	Cerebellar ataxia	Pubtator	32234020	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar Diseases	BEFREE	14966165, 16037936		★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	BEFREE	14635118, 15668446, 17420318, 18195150, 18575922, 19705478, 20479361, 20659899, 20803511, 21301859, 24014582, 24018892, 26689116, 26838077, 28762753		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	LHGDN	17722119, 18575922, 18971204		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital pes cavus	Congenital Pes Cavus	CLINVAR_DG	27551684		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	25193669		★☆☆☆☆ Found in Text Mining only
Deafness	Deafness	Pubtator	32234020, 33095980	Associate	★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	BEFREE	18980793		★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dentatorubral-Pallidoluysian Atrophy	Dentatorubral Pallidoluysian Atrophy	BEFREE	11448300, 11939898, 26538302, 28708110		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	29253968		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder	Major depressive disorder	Pubtator	31852434	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive disorder	Mental Depression	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive disorder	Mental Depression	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	BEFREE	30799093		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsia Partialis Continua	Epilepsia Partialis Continua	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	20495966, 20803511, 22459315, 28130605		★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Episodic Ataxia	Episodic Ataxia	BEFREE	14747838		★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	25817828		★☆☆☆☆ Found in Text Mining only
Esophageal Achalasia	Achalasia	BEFREE	28130605		★☆☆☆☆ Found in Text Mining only
Essential Tremor	Tremor	BEFREE	26077168		★☆☆☆☆ Found in Text Mining only
External Ophthalmoplegia	External Ophthalmoplegia	BEFREE	21689831		★☆☆☆☆ Found in Text Mining only
External Ophthalmoplegia	External Ophthalmoplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fragile X Syndrome	Fragile X Syndrome	BEFREE	11807410		★☆☆☆☆ Found in Text Mining only
Friedreich Ataxia	Friedreich Ataxia	BEFREE	24011957		★☆☆☆☆ Found in Text Mining only
Gallbladder Carcinoma	Gallbladder cancer	BEFREE	29630938		★☆☆☆☆ Found in Text Mining only
Gastroesophageal reflux disease	Gastroesophageal Reflux Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gastroparesis	Gastroparesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis	Gonadal dysgenesis	Pubtator	31852434	Associate	★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis	Gonadal Dysgenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis 46 XX	46, xx gonadal dysgenesis	Pubtator	39529088	Associate	★☆☆☆☆ Found in Text Mining only
Gonadal dysgenesis XX type deafness	Gonadal Dysgenesis	ORPHANET_DG	25355836		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gonadal dysgenesis XX type deafness	Gonadal dysgenesis	Pubtator	25355836, 28178980, 31455392, 31852434, 32234020, 37932750, 38295749, 39340975	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gonadal dysgenesis XX type deafness	Gonadal Dysgenesis	BEFREE	25956234, 26657938, 27087618, 28178980, 31455392		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing Disorders	Headache	Pubtator	39684270	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	28178980, 31852434	Associate	★☆☆☆☆ Found in Text Mining only
Hepatic Encephalopathy	Hepatic encephalopathy	Pubtator	20659899, 31455392	Associate	★☆☆☆☆ Found in Text Mining only
Hepatic Encephalopathy	Hepatic Encephalopathy	BEFREE	31455392		★☆☆☆☆ Found in Text Mining only
HUNTINGTON DISEASE-LIKE 2	Huntington Disease-Like	BEFREE	28987184		★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	28708110		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inclusion Body Myositis (disorder)	Inclusion Body Myositis	BEFREE	25638290		★☆☆☆☆ Found in Text Mining only
Infantile onset spinocerebellar ataxia	Spinocerebellar Ataxia	BEFREE	16135556, 18775955, 20659899, 22353293, 24816431, 31823625, 9027505		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Infantile onset spinocerebellar ataxia	Spinocerebellar Ataxia	UNIPROT_DG	16135556, 17722119, 17921179, 19853444, 22353293		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Infantile onset spinocerebellar ataxia	Spinocerebellar Ataxia	GENOMICS_ENGLAND_DG	19513767, 27604308, 30391088		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Infantile onset spinocerebellar ataxia	Spinocerebellar Ataxia	CLINVAR_DG	27551684		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Infantile onset spinocerebellar ataxia	Spinocerebellar Ataxia	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Infantile-onset spinocerebellar ataxia	Spinocerebellar Ataxia	Orphanet			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	24816431	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	27121845		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intestinal Pseudo-Obstruction	Intestinal Pseudoobstruction	HPO_DG			★☆☆☆☆ Found in Text Mining only
Kearns-Sayre syndrome	Kearns Sayre Syndrome	BEFREE	29310369, 9375854		★☆☆☆☆ Found in Text Mining only
Ketosis	Ketosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Left Ventricular Hypertrophy	Left Ventricular Hypertrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Machado-Joseph Disease	Machado-Joseph Disease	BEFREE	11939898		★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 1	Major Affective Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 2	Major Affective Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 4	Major Affective Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 6	Major Affective Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 7	Major Affective Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 8	Major Affective Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
MAJOR AFFECTIVE DISORDER 9	Major Affective Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of gallbladder	Gallbladder cancer	BEFREE	29630938		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	19654294, 21385444, 24895135, 25684390, 27935869, 29410730		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28821788		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	27527491		★☆☆☆☆ Found in Text Mining only
MELAS Syndrome	MELAS Syndrome	BEFREE	30138712, 7912129		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	29253968		★☆☆☆☆ Found in Text Mining only
MERRF Syndrome	Myoclonic epilepsy with ragged red fibers	Pubtator	21689831	Associate	★☆☆☆☆ Found in Text Mining only
Migraine Disorders	Migraine	BEFREE	20495966		★☆☆☆☆ Found in Text Mining only
Migraine Disorders	Migraine	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	20659899, 20803511, 22176657, 22952820, 23107649, 24011957, 24985751		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	20659899	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	CLINVAR_DG	28812649		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial DNA depletion syndrome, hepatocerebrorenal form	Mitochondrial DNA Depletion Syndrome, hepatocerebral	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Encephalomyopathies	Mitochondrial encephalomyopathy	Pubtator	33396418	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial encephalopathy	Mitochondrial encephalopathy	BEFREE	30138712		★☆☆☆☆ Found in Text Mining only
Mitochondrial Myopathies	Mitochondrial myopathy	BEFREE	24014582		★☆☆☆☆ Found in Text Mining only
Mitochondrial Myopathies	Mitochondrial myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	22872568		★☆☆☆☆ Found in Text Mining only
Myasthenia Gravis	Myasthenia Gravis	BEFREE	24014582		★☆☆☆☆ Found in Text Mining only
Myasthenia Gravis	Myasthenia gravis	Pubtator	24014582	Associate	★☆☆☆☆ Found in Text Mining only
Myasthenic Syndromes Congenital	Myasthenic syndrome	Pubtator	24014582	Associate	★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	15258213, 24816431		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	LHGDN	17614277		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30311803		★☆☆☆☆ Found in Text Mining only
Nephrocalcinosis	Nephrocalcinosis	BEFREE	30799093		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	10713882		★☆☆☆☆ Found in Text Mining only
Neuromuscular dysphagia	Neuromuscular dysphagia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	15668446, 28130605, 28722203		★☆☆☆☆ Found in Text Mining only
Nocturia	Nocturia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nonorganic psychosis	Nonorganic Psychosis	BEFREE	10813808		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia	Ophthalmoplegia	Pubtator	20659899, 21689831, 24018892	Associate	★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia Chronic Progressive External	Progressive external ophthalmoplegia	Pubtator	18195150, 21301859, 21689831, 24014582, 24018892, 24086434, 32234020, 37316776	Associate	★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	BEFREE	18575922, 19015050		★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	CLINVAR_DG	27551684		★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy, Hereditary, Leber	Hereditary Leber Optic Atrophy	BEFREE	19015050		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ovarian adenocarcinoma	Ovarian adenocarcinoma	BEFREE	15870720		★☆☆☆☆ Found in Text Mining only
Ovarian Carcinoma	Ovarian Carcinoma	BEFREE	19654294		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	21385444, 24895135, 25684390, 27935869, 29410730		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	1586592, 19654294, 27465688, 38114660	Associate	★☆☆☆☆ Found in Text Mining only
Paraparesis Spastic	Paraparesis	Pubtator	31852434	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	14756671, 19788048, 25866756		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	LHGDN	17620490		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	19788048, 35792653	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease Secondary	Secondary parkinson disease	Pubtator	21301859, 35792653	Associate	★☆☆☆☆ Found in Text Mining only
Parkinsonian Disorders	Parkinson Disease	BEFREE	21301859, 24076137, 30788857		★☆☆☆☆ Found in Text Mining only
Peripheral axonal neuropathy	Peripheral axonal neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral motor neuropathy	Motor nerve neuritis	BEFREE	24816431		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	24816431, 32234020	Associate	★☆☆☆☆ Found in Text Mining only
Perrault syndrome	Perrault Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PERRAULT SYNDROME 5	Perrault Syndrome	GENOMICS_ENGLAND_DG	19513767, 25355836		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PERRAULT SYNDROME 5	Perrault Syndrome	UNIPROT_DG	25355836		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PERRAULT SYNDROME 5	Perrault Syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Polyneuropathies	Polyneuropathy	Pubtator	24816431, 31852434	Associate	★☆☆☆☆ Found in Text Mining only
Premature aging syndrome	Premature aging	BEFREE	26689116		★☆☆☆☆ Found in Text Mining only
Primary hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive cerebellar ataxia	Cerebellar Ataxia	BEFREE	12140678		★☆☆☆☆ Found in Text Mining only
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 1	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	ORPHANET_DG	11431692, 21519523		★☆☆☆☆ Found in Text Mining only
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 3	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	UNIPROT_DG	11431692, 12163192, 12921794, 15668446, 16639411, 17614277, 18396044, 18575922, 19353676, 19428252, 20479361, 20880070		★☆☆☆☆ Found in Text Mining only
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 3	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	CLINVAR_DG	17614277, 20479361, 20659899, 24018892		★☆☆☆☆ Found in Text Mining only
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 3	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	GENOMICS_ENGLAND_DG	19513767, 27604308, 30391088		★☆☆☆☆ Found in Text Mining only
Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 3	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	BEFREE	10813808		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	BEFREE	24018892		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	25193669		★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	29310369		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural hearing loss, bilateral	Sensorineural hearing loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural hearing loss, bilateral	Sensorineural hearing loss	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Sensory ataxic neuropathy dysarthria and ophthalmoparesis	Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Pubtator	33396418	Associate	★☆☆☆☆ Found in Text Mining only
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Ataxia neuropathy spectrum disorder	ORPHANET_DG	15668446		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Ataxia neuropathy spectrum disorder	BEFREE	25203713		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	Ataxia neuropathy spectrum disorder	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome	Sensory Ataxic Neuropathy-Dysarthria-Ophthalmoparesis Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensory neuropathy	Sensory neuropathy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Skin Erosion	Skin Erosion	BEFREE	29391794		★☆☆☆☆ Found in Text Mining only
Specific learning disability	Specific Learning Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
SPINOCEREBELLAR ATAXIA 8	Spinocerebellar Ataxia	BEFREE	14966165, 17961920, 18095954, 18418692, 18980793, 19203395, 22577844, 26077168		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxia Type 6 (disorder)	Spinocerebellar Ataxia	BEFREE	28987184		★☆☆☆☆ Found in Text Mining only
Spinocerebellar Ataxias	Spinocerebellar ataxia	Pubtator	20659899, 24816431	Associate	★☆☆☆☆ Found in Text Mining only
Status Epilepticus	Status Epilepticus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thrombotic Microangiopathies	Thrombotic Microangiopathies	BEFREE	27864296		★☆☆☆☆ Found in Text Mining only
Upgaze palsy	Upgaze palsy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular arrhythmia	Ventricular arrhythmia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Visceral myopathy familial external ophthalmoplegia	Visceral neuropathy	Pubtator	19667227, 20659899, 31455269, 36311265	Associate	★☆☆☆☆ Found in Text Mining only