TOP3A (DNA topoisomerase III alpha)

Gene

• Entrez ID: 7156
• Gene name: DNA topoisomerase III alpha
• Gene symbol: TOP3A
• Synonyms (NCBI Gene): MGRISCE2, PEOB5, TOP3, ZGRF7
• Chromosome: 17
• Chromosome location: 17p11.2
• Summary: This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200944917	G>A,T	Pathogenic	Synonymous variant, stop gained, coding sequence variant, 5 prime UTR variant, non coding transcript variant
rs376902371	T>C	Pathogenic	Intron variant, coding sequence variant, 5 prime UTR variant, missense variant, non coding transcript variant, genic upstream transcript variant
rs752838075	G>-,GG	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1288928564	C>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs1555568139	A>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1597981046	TA>-	Likely-pathogenic	Frameshift variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT046639	hsa-miR-222-3p	CLASH	23622248
MIRT044415	hsa-miR-320a	CLASH	23622248
MIRT680154	hsa-miR-5571-5p	HITS-CLIP	23824327
MIRT680153	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT680152	hsa-miR-4324	HITS-CLIP	23824327
MIRT680151	hsa-miR-544b	HITS-CLIP	23824327
MIRT680150	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT680149	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT680148	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT680146	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT680147	hsa-miR-1976	HITS-CLIP	23824327
MIRT680145	hsa-miR-6791-3p	HITS-CLIP	23824327
MIRT680144	hsa-miR-6829-3p	HITS-CLIP	23824327
MIRT680143	hsa-miR-1200	HITS-CLIP	23824327
MIRT680142	hsa-miR-4279	HITS-CLIP	23824327
MIRT680141	hsa-miR-6869-5p	HITS-CLIP	23824327
MIRT680154	hsa-miR-5571-5p	HITS-CLIP	23824327
MIRT680153	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT680152	hsa-miR-4324	HITS-CLIP	23824327
MIRT680151	hsa-miR-544b	HITS-CLIP	23824327
MIRT680150	hsa-miR-4722-3p	HITS-CLIP	23824327
MIRT680149	hsa-miR-6727-3p	HITS-CLIP	23824327
MIRT680148	hsa-miR-6747-3p	HITS-CLIP	23824327
MIRT680146	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT680147	hsa-miR-1976	HITS-CLIP	23824327
MIRT680145	hsa-miR-6791-3p	HITS-CLIP	23824327
MIRT680144	hsa-miR-6829-3p	HITS-CLIP	23824327
MIRT680143	hsa-miR-1200	HITS-CLIP	23824327
MIRT680142	hsa-miR-4279	HITS-CLIP	23824327
MIRT680141	hsa-miR-6869-5p	HITS-CLIP	23824327
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT1447308	hsa-miR-138	CLIP-seq
MIRT1447309	hsa-miR-141	CLIP-seq
MIRT1447310	hsa-miR-200a	CLIP-seq
MIRT1447311	hsa-miR-24	CLIP-seq
MIRT1447312	hsa-miR-3180-5p	CLIP-seq
MIRT1447313	hsa-miR-3614-5p	CLIP-seq
MIRT1447314	hsa-miR-3670	CLIP-seq
MIRT1447315	hsa-miR-3909	CLIP-seq
MIRT1447316	hsa-miR-4260	CLIP-seq
MIRT1447317	hsa-miR-4269	CLIP-seq
MIRT1447318	hsa-miR-4283	CLIP-seq
MIRT1447319	hsa-miR-4284	CLIP-seq
MIRT1447320	hsa-miR-4456	CLIP-seq
MIRT1447321	hsa-miR-4489	CLIP-seq
MIRT1447322	hsa-miR-4514	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT1447324	hsa-miR-4692	CLIP-seq
MIRT1447325	hsa-miR-4742-5p	CLIP-seq
MIRT1447326	hsa-miR-4772-3p	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT1447328	hsa-miR-512-3p	CLIP-seq
MIRT1447329	hsa-miR-513a-3p	CLIP-seq
MIRT1447330	hsa-miR-665	CLIP-seq
MIRT2133726	hsa-miR-1234	CLIP-seq
MIRT2133727	hsa-miR-1275	CLIP-seq
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT2133728	hsa-miR-214	CLIP-seq
MIRT2133729	hsa-miR-302a	CLIP-seq
MIRT2133730	hsa-miR-302b	CLIP-seq
MIRT2133731	hsa-miR-302c	CLIP-seq
MIRT2133732	hsa-miR-302d	CLIP-seq
MIRT2133733	hsa-miR-302e	CLIP-seq
MIRT2133734	hsa-miR-3120-3p	CLIP-seq
MIRT2133735	hsa-miR-3130-3p	CLIP-seq
MIRT2133736	hsa-miR-3164	CLIP-seq
MIRT2133737	hsa-miR-3189-3p	CLIP-seq
MIRT2133738	hsa-miR-3619-5p	CLIP-seq
MIRT2133739	hsa-miR-362-5p	CLIP-seq
MIRT1447314	hsa-miR-3670	CLIP-seq
MIRT2133740	hsa-miR-372	CLIP-seq
MIRT2133741	hsa-miR-373	CLIP-seq
MIRT2133742	hsa-miR-4252	CLIP-seq
MIRT1447317	hsa-miR-4269	CLIP-seq
MIRT2133743	hsa-miR-4291	CLIP-seq
MIRT2133744	hsa-miR-4419a	CLIP-seq
MIRT2133745	hsa-miR-4438	CLIP-seq
MIRT2133746	hsa-miR-4510	CLIP-seq
MIRT1447322	hsa-miR-4514	CLIP-seq
MIRT2133747	hsa-miR-4519	CLIP-seq
MIRT2133748	hsa-miR-4520a-5p	CLIP-seq
MIRT2133749	hsa-miR-4520b-5p	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT2133750	hsa-miR-4665-5p	CLIP-seq
MIRT1447324	hsa-miR-4692	CLIP-seq
MIRT2133751	hsa-miR-4731-5p	CLIP-seq
MIRT1447325	hsa-miR-4742-5p	CLIP-seq
MIRT1447326	hsa-miR-4772-3p	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT2133752	hsa-miR-500b	CLIP-seq
MIRT2133753	hsa-miR-5095	CLIP-seq
MIRT1447328	hsa-miR-512-3p	CLIP-seq
MIRT2133754	hsa-miR-520a-3p	CLIP-seq
MIRT2133755	hsa-miR-520b	CLIP-seq
MIRT2133756	hsa-miR-520c-3p	CLIP-seq
MIRT2133757	hsa-miR-520d-3p	CLIP-seq
MIRT2133758	hsa-miR-520e	CLIP-seq
MIRT2133759	hsa-miR-615-5p	CLIP-seq
MIRT2133760	hsa-miR-646	CLIP-seq
MIRT2133761	hsa-miR-661	CLIP-seq
MIRT2133762	hsa-miR-761	CLIP-seq
MIRT2133763	hsa-miR-922	CLIP-seq
MIRT2133764	hsa-miR-941	CLIP-seq
MIRT2354878	hsa-miR-1207-3p	CLIP-seq
MIRT2354879	hsa-miR-1228	CLIP-seq
MIRT2133726	hsa-miR-1234	CLIP-seq
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT2354880	hsa-miR-1288	CLIP-seq
MIRT2354881	hsa-miR-129-5p	CLIP-seq
MIRT2354882	hsa-miR-139-5p	CLIP-seq
MIRT2354883	hsa-miR-197	CLIP-seq
MIRT2133735	hsa-miR-3130-3p	CLIP-seq
MIRT2354884	hsa-miR-3149	CLIP-seq
MIRT2354885	hsa-miR-3199	CLIP-seq
MIRT2354886	hsa-miR-33a	CLIP-seq
MIRT2354887	hsa-miR-33b	CLIP-seq
MIRT2354888	hsa-miR-3618	CLIP-seq
MIRT1447314	hsa-miR-3670	CLIP-seq
MIRT2354889	hsa-miR-411	CLIP-seq
MIRT2133742	hsa-miR-4252	CLIP-seq
MIRT1447317	hsa-miR-4269	CLIP-seq
MIRT2133745	hsa-miR-4438	CLIP-seq
MIRT1447322	hsa-miR-4514	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT1447324	hsa-miR-4692	CLIP-seq
MIRT2354890	hsa-miR-4716-5p	CLIP-seq
MIRT2133751	hsa-miR-4731-5p	CLIP-seq
MIRT2354891	hsa-miR-4735-5p	CLIP-seq
MIRT1447325	hsa-miR-4742-5p	CLIP-seq
MIRT2354892	hsa-miR-4775	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT2354893	hsa-miR-502-5p	CLIP-seq
MIRT2133753	hsa-miR-5095	CLIP-seq
MIRT2354894	hsa-miR-5096	CLIP-seq
MIRT1447328	hsa-miR-512-3p	CLIP-seq
MIRT2354895	hsa-miR-590-3p	CLIP-seq
MIRT2133761	hsa-miR-661	CLIP-seq
MIRT2354896	hsa-miR-767-5p	CLIP-seq
MIRT2133764	hsa-miR-941	CLIP-seq
MIRT2396209	hsa-miR-3121-5p	CLIP-seq
MIRT1447314	hsa-miR-3670	CLIP-seq
MIRT1447317	hsa-miR-4269	CLIP-seq
MIRT1447322	hsa-miR-4514	CLIP-seq
MIRT1447324	hsa-miR-4692	CLIP-seq
MIRT1447325	hsa-miR-4742-5p	CLIP-seq
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT2648632	hsa-miR-1184	CLIP-seq
MIRT2648633	hsa-miR-1205	CLIP-seq
MIRT2354878	hsa-miR-1207-3p	CLIP-seq
MIRT2354879	hsa-miR-1228	CLIP-seq
MIRT2648634	hsa-miR-1252	CLIP-seq
MIRT2648635	hsa-miR-125a-3p	CLIP-seq
MIRT2648636	hsa-miR-1271	CLIP-seq
MIRT2648637	hsa-miR-128	CLIP-seq
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT2354880	hsa-miR-1288	CLIP-seq
MIRT2354881	hsa-miR-129-5p	CLIP-seq
MIRT1447308	hsa-miR-138	CLIP-seq
MIRT2648638	hsa-miR-182	CLIP-seq
MIRT1447311	hsa-miR-24	CLIP-seq
MIRT2396209	hsa-miR-3121-5p	CLIP-seq
MIRT2133735	hsa-miR-3130-3p	CLIP-seq
MIRT2354884	hsa-miR-3149	CLIP-seq
MIRT2648639	hsa-miR-3158-5p	CLIP-seq
MIRT2648640	hsa-miR-3160-5p	CLIP-seq
MIRT2648641	hsa-miR-3189-5p	CLIP-seq
MIRT2648642	hsa-miR-3192	CLIP-seq
MIRT2354885	hsa-miR-3199	CLIP-seq
MIRT1447313	hsa-miR-3614-5p	CLIP-seq
MIRT2648643	hsa-miR-3665	CLIP-seq
MIRT1447316	hsa-miR-4260	CLIP-seq
MIRT1447318	hsa-miR-4283	CLIP-seq
MIRT1447319	hsa-miR-4284	CLIP-seq
MIRT2648644	hsa-miR-4292	CLIP-seq
MIRT2648645	hsa-miR-4300	CLIP-seq
MIRT2648646	hsa-miR-4417	CLIP-seq
MIRT1447320	hsa-miR-4456	CLIP-seq
MIRT1447321	hsa-miR-4489	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT2354891	hsa-miR-4735-5p	CLIP-seq
MIRT2648647	hsa-miR-4758-3p	CLIP-seq
MIRT2354892	hsa-miR-4775	CLIP-seq
MIRT2648648	hsa-miR-4778-3p	CLIP-seq
MIRT2648649	hsa-miR-4794	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT1447328	hsa-miR-512-3p	CLIP-seq
MIRT2648650	hsa-miR-544	CLIP-seq
MIRT2354895	hsa-miR-590-3p	CLIP-seq
MIRT2648651	hsa-miR-657	CLIP-seq
MIRT2354896	hsa-miR-767-5p	CLIP-seq
MIRT2648652	hsa-miR-920	CLIP-seq
MIRT2648653	hsa-miR-96	CLIP-seq
MIRT2648632	hsa-miR-1184	CLIP-seq
MIRT2648633	hsa-miR-1205	CLIP-seq
MIRT2354879	hsa-miR-1228	CLIP-seq
MIRT2648634	hsa-miR-1252	CLIP-seq
MIRT2648635	hsa-miR-125a-3p	CLIP-seq
MIRT2648636	hsa-miR-1271	CLIP-seq
MIRT2648637	hsa-miR-128	CLIP-seq
MIRT1447307	hsa-miR-1281	CLIP-seq
MIRT2354881	hsa-miR-129-5p	CLIP-seq
MIRT1447308	hsa-miR-138	CLIP-seq
MIRT2648638	hsa-miR-182	CLIP-seq
MIRT1447311	hsa-miR-24	CLIP-seq
MIRT2396209	hsa-miR-3121-5p	CLIP-seq
MIRT2354884	hsa-miR-3149	CLIP-seq
MIRT2648639	hsa-miR-3158-5p	CLIP-seq
MIRT2648640	hsa-miR-3160-5p	CLIP-seq
MIRT2648641	hsa-miR-3189-5p	CLIP-seq
MIRT2648642	hsa-miR-3192	CLIP-seq
MIRT1447313	hsa-miR-3614-5p	CLIP-seq
MIRT2648643	hsa-miR-3665	CLIP-seq
MIRT2354889	hsa-miR-411	CLIP-seq
MIRT1447316	hsa-miR-4260	CLIP-seq
MIRT1447318	hsa-miR-4283	CLIP-seq
MIRT1447319	hsa-miR-4284	CLIP-seq
MIRT2648644	hsa-miR-4292	CLIP-seq
MIRT2648645	hsa-miR-4300	CLIP-seq
MIRT2648646	hsa-miR-4417	CLIP-seq
MIRT1447320	hsa-miR-4456	CLIP-seq
MIRT1447321	hsa-miR-4489	CLIP-seq
MIRT1447323	hsa-miR-4532	CLIP-seq
MIRT2354891	hsa-miR-4735-5p	CLIP-seq
MIRT2648647	hsa-miR-4758-3p	CLIP-seq
MIRT2354892	hsa-miR-4775	CLIP-seq
MIRT2648648	hsa-miR-4778-3p	CLIP-seq
MIRT2648649	hsa-miR-4794	CLIP-seq
MIRT1447327	hsa-miR-498	CLIP-seq
MIRT1447328	hsa-miR-512-3p	CLIP-seq
MIRT2648650	hsa-miR-544	CLIP-seq
MIRT2354895	hsa-miR-590-3p	CLIP-seq
MIRT2648651	hsa-miR-657	CLIP-seq
MIRT2648652	hsa-miR-920	CLIP-seq
MIRT2648653	hsa-miR-96	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
USF1	Activation	9748294
USF2	Activation	11557042
YY1	Activation	9748294

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000724	Process	Double-strand break repair via homologous recombination	IDA	23543748
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	8622991
GO:0003697	Function	Single-stranded DNA binding	IDA	29290614
GO:0003916	Function	DNA topoisomerase activity	IEA
GO:0003917	Function	DNA topoisomerase type I (single strand cut, ATP-independent) activity	IBA
GO:0003917	Function	DNA topoisomerase type I (single strand cut, ATP-independent) activity	IDA	20445207
GO:0003917	Function	DNA topoisomerase type I (single strand cut, ATP-independent) activity	IEA
GO:0005515	Function	Protein binding	IPI	10728666, 15775963, 16537486, 20360068, 20711169, 20826342, 23509288, 24509834, 26496610, 33961781, 35271311
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	NAS	23543748
GO:0005634	Component	Nucleus	TAS	8622991
GO:0005654	Component	Nucleoplasm	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006265	Process	DNA topological change	IBA
GO:0006265	Process	DNA topological change	IDA	20445207
GO:0006265	Process	DNA topological change	IEA
GO:0006281	Process	DNA repair	IBA
GO:0006310	Process	DNA recombination	IBA
GO:0008270	Function	Zinc ion binding	IEA
GO:0016605	Component	PML body	IDA	10728666
GO:0016853	Function	Isomerase activity	IEA
GO:0031422	Component	RecQ family helicase-topoisomerase III complex	IBA
GO:0031422	Component	RecQ family helicase-topoisomerase III complex	IPI	24984776
GO:0032042	Process	Mitochondrial DNA metabolic process	IMP	29290614
GO:0046872	Function	Metal ion binding	IEA
GO:0051304	Process	Chromosome separation	IMP	30057030
GO:0051321	Process	Meiotic cell cycle	TAS	8622991
GO:0071139	Process	Resolution of DNA recombination intermediates	IDA	23543748

Other IDs

• MIM: 601243
• HGNC: 11992
• e!Ensembl: ENSG00000177302

Protein

• UniProt ID: Q13472
• Protein name: DNA topoisomerase 3-alpha (EC 5.6.2.1) (DNA topoisomerase III alpha)
• Protein function: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a targ
• PDB: 4CGY, 4CHT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01751	Toprim	36 → 181	Toprim domain	Family
  PF01131	Topoisom_bac	195 → 607	DNA topoisomerase	Family
  PF01396	zf-C4_Topoisom	655 → 694	Topoisomerase DNA binding C4 zinc finger	Family
  PF06839	zf-GRF	811 → 852	GRF zinc finger	Domain
  PF06839	zf-GRF	895 → 939	GRF zinc finger	Domain

• Tissue specificity: TISSUE SPECIFICITY: High expression is found in testis, heart, skeletal muscle and pancreas.
• Sequence:

  MIFPVARYALRWLRRPEDRAFSRAAMEMALRGVRKVLCVAEKNDAAKGIADLLSNGRMRR
  REGLSKFNKIYEFDYHLYGQNVTMVMTSVSGHLLAHDFQMQFRKWQSCNPLVLFEAEIEK
  YCPENFVDIKKTLERETRQCQALVIWTDCDREGENIGFEIIHVCKAVKPNLQVLRARFSE
  ITPHAVRTACENLTEPDQRVSDAVDVRQELDLRIGAAFTRFQTLRLQRIFPEVLAEQLIS
  YGSCQFPTLGFVVERFKAIQAFVPEIFHRIKVTHDHKDGIVEFNWKRHRLFNHTACLVLY
  QLCVEDPMATVVEVRSKPKSKWRPQALDTVELEKLASRKLRINAKETMRIAEKLYTQGYI
  SYPRTETNIFPRDLNLTVLVEQQTPDPRWGAFAQSILERGGPTPRNGNKSDQAHPPIHPT
  KYTNNLQGDEQRLYEFIVRHFLACCSQDAQGQETTVEIDIAQERFVAHGLMILARNYLDV
  YPYDHWSDKILPVYEQGSHFQPSTVEMVDGETSPPKLLTEADLIALMEKHGIGTDATHAE
  HIETIKARMYVGLTPDKRFLPGHLGMGLVEGYDSMGYEMSKPDLRAELEADLKLICDGKK
  DKFVVLRQQVQKYKQVFIEAVAKAKKLDEALAQYFGNGTELAQQEDIYPAMPEPIRKCPQ
  CNKDMVLKTKKNGGFYLSCMGFPECRSAVWLPDSVLEASRDSSVCPVCQPHPVYRLKLKF
  KRGSLPPTMPLEFVCCIGGCDDTLREILDLRFSGGPPRASQPSGRLQANQSLNRMDNSQH
  PQPADSRQTGSSKALAQTLPPPTAAGESNSVTCNCGQEAVLLTVRKEGPNRGRQFFKCNG
  GSCNFFLWADSPNPGAGGPPALAYRPLGASLGCPPGPGIHLGGFGNPGDGSGSGTSCLCS
  QPSVTRTVQKDGPNKGRQFHTCAKPREQQCGFFQWVDENTAPGTSGAPSWTGDRGRTLES
  EARSKRPRASSSDMGSTAKKPRKCSLCHQPGHTRPFCPQNR

• Sequence length: 1001

Pathways

KEGG:

Homologous recombination
Fanconi anemia pathway

Reactome:

HDR through Single Strand Annealing (SSA)
HDR through Homologous Recombination (HRR)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
Resolution of D-loop Structures through Holliday Junction Intermediates
Homologous DNA Pairing and Strand Exchange
Processing of DNA double-strand break ends
Presynaptic phase of homologous DNA pairing and strand exchange
Regulation of TP53 Activity through Phosphorylation
G2/M DNA damage checkpoint

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
Microcephaly, growth restriction, and increased sister chromatid exchange 2	Likely pathogenic; Pathogenic	rs200150335, rs1288928564, rs752838075, rs1555568139	RCV004594678 RCV000678245 RCV000678246 RCV000678247	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial disease	Pathogenic	rs200944917, rs376902371	RCV000627803 RCV000627802	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5	Pathogenic; Likely pathogenic	rs1181170417, rs200944917, rs376902371, rs1597981046	RCV003890773 RCV000678503 RCV000678502 RCV000787954	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL RECESSIVE PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE SCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensorineural hearing loss disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TOP3A-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UTERINE FIBROID	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	28355294		★☆☆☆☆ Found in Text Mining only
Alternating hemiplegia of childhood	Alternating hemiplegia of childhood	Pubtator	28877996, 31138797	Associate	★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	BEFREE	22102081		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	19432957		★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bloom Syndrome	Bloom Syndrome	BEFREE	30057030		★☆☆☆☆ Found in Text Mining only
Bloom Syndrome	Bloom syndrome	Pubtator	33631320, 35119917, 37013609	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	19432957		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	19432957	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	19432957		★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	27315793	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	BEFREE	29290614		★☆☆☆☆ Found in Text Mining only
Chronic progressive external ophthalmoplegia	Progressive External Ophthalmoplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	30057030		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	33713422	Associate	★☆☆☆☆ Found in Text Mining only
Hepatomegaly	Hepatomegaly	Pubtator	33631320	Associate	★☆☆☆☆ Found in Text Mining only
	Intrauterine Growth Restriction, Congenital Multiple Caf -Au-Lait Macules-Increased Sister Chromatid Exchange Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	28355294	Stimulate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	19432957		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	19432957		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	19432957		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	19432957		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Microcephaly	BEFREE	30057030		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE 2	MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE	UNIPROT_DG	30057030		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE 2	MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE 2	MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE	GENOMICS_ENGLAND_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	29290614		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	CLINVAR_DG	29290614		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	29290614, 33631320, 37013609	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple Sclerosis	Multiple Sclerosis	GWASCAT_DG	27386562		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	28355294		★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia	Ophthalmoplegia	Pubtator	37013609	Associate	★☆☆☆☆ Found in Text Mining only
Ophthalmoplegia Chronic Progressive External	Progressive external ophthalmoplegia	Pubtator	29290614	Associate	★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	12550767		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	22292074, 35920001	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	37013609	Associate	★☆☆☆☆ Found in Text Mining only
Premature aging syndrome	Premature aging	BEFREE	20157511		★☆☆☆☆ Found in Text Mining only
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 5	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	UNIPROT_DG	29290614		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 5	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions	GENOMICS_ENGLAND_DG	29290614		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensory neuropathy	Sensory neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of lung	Lung carcinoma	BEFREE	28355294		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	25921176	Associate	★☆☆☆☆ Found in Text Mining only
Werner Syndrome	Werner Syndrome	BEFREE	20157511		★☆☆☆☆ Found in Text Mining only