TOP3B

Summary

TOP3B (DNA topoisomerase III beta, HGNC:11993) is a protein-coding gene on chromosome 22q11.22, encoding DNA topoisomerase 3-beta-1 (O95985). 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.

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 another, thus relaxing the supercoils and altering the topology of DNA. The enzyme interacts with DNA helicase SGS1 and plays a role in DNA recombination, cellular aging and maintenance of genome stability. Low expression of this gene may be related to higher survival rates in breast cancer patients. This gene has a pseudogene on chromosome 22. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 8940 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 177 total — 1 likely-pathogenic
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001282112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11993
Approved symbol	TOP3B
Name	DNA topoisomerase III beta
Location	22q11.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100038
Ensembl biotype	protein_coding
OMIM	603582
Entrez	8940

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 23 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000357179, ENST00000398793, ENST00000424393, ENST00000430142, ENST00000434517, ENST00000436282, ENST00000437103, ENST00000437929, ENST00000442653, ENST00000444502, ENST00000449704, ENST00000456075, ENST00000457179, ENST00000457270, ENST00000470338, ENST00000487485, ENST00000489581, ENST00000868094, ENST00000868095, ENST00000868096, ENST00000937943, ENST00000937944, ENST00000937945, ENST00000937946, ENST00000937947, ENST00000968013, ENST00000968014, ENST00000968015, ENST00000968016

RefSeq mRNA: 9 — MANE Select: NM_001282112 NM_001282112, NM_001282113, NM_001349845, NM_001349847, NM_001349848, NM_001349850, NM_001349851, NM_001349852, NM_003935

CCDS: CCDS13797

Canonical transcript exons

ENST00000357179 — 18 exons

Exon	Start	End
ENSE00001646255	21982730	21982787
ENSE00001756605	21971877	21971951
ENSE00001915921	21957025	21957595
ENSE00003465334	21960321	21960449
ENSE00003501188	21959132	21959232
ENSE00003522122	21963923	21964028
ENSE00003559313	21958492	21958693
ENSE00003577002	21962747	21962893
ENSE00003589652	21970210	21970406
ENSE00003593806	21962429	21962602
ENSE00003621283	21974357	21974488
ENSE00003633449	21959587	21959736
ENSE00003640448	21965285	21965375
ENSE00003662250	21975640	21975807
ENSE00003681474	21972612	21972718
ENSE00003687408	21967603	21967716
ENSE00003694535	21964161	21964315
ENSE00003787669	21968619	21968775

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 98.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3454 / max 407.5023, expressed in 1797 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193261	17.1978	1796
193262	0.8948	342
193260	0.2527	100

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	98.41	gold quality
middle frontal gyrus	UBERON:0002702	98.39	gold quality
frontal pole	UBERON:0002795	98.37	gold quality
endometrium epithelium	UBERON:0004811	96.06	gold quality
granulocyte	CL:0000094	90.71	gold quality
lower esophagus mucosa	UBERON:0035834	90.04	gold quality
right ovary	UBERON:0002118	87.88	gold quality
metanephros cortex	UBERON:0010533	87.83	gold quality
stromal cell of endometrium	CL:0002255	87.26	gold quality
left ovary	UBERON:0002119	87.08	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.25	gold quality
body of uterus	UBERON:0009853	86.16	gold quality
endocervix	UBERON:0000458	86.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.92	gold quality
apex of heart	UBERON:0002098	85.84	gold quality
spleen	UBERON:0002106	85.83	gold quality
skin of leg	UBERON:0001511	85.82	gold quality
right lobe of liver	UBERON:0001114	85.61	gold quality
mucosa of transverse colon	UBERON:0004991	85.51	gold quality
right lobe of thyroid gland	UBERON:0001119	85.47	gold quality
right uterine tube	UBERON:0001302	85.24	gold quality
transverse colon	UBERON:0001157	85.18	gold quality
body of stomach	UBERON:0001161	85.17	gold quality
skin of abdomen	UBERON:0001416	85.15	gold quality
cerebellar hemisphere	UBERON:0002245	85.10	gold quality
tibial nerve	UBERON:0001323	85.04	gold quality
cerebellar cortex	UBERON:0002129	84.97	gold quality
minor salivary gland	UBERON:0001830	84.89	gold quality
right adrenal gland	UBERON:0001233	84.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.20

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 15)

• Two isoforms of human DNA topoisomerase IIIbeta were expressed in HeLa cells. Isoform 1 was localized to the nucleus and associated with chromosomes during metaphase and anaphase. Isoform 2 was found in the cytoplasm. (PMID:11549288)
• the positive regulatory region including the 5’GGAACC3’ core element is essential for efficient expression of the DNA topoisomerase III beta gene (PMID:15358519)
• Topoisomerase IIIbeta expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival. (PMID:20950730)
• TOP3B promotes transcription, protects against DNA damage, and reduces the frequency of chromosomal translocations. (PMID:24507716)
• Top3b proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3b-polyribosome association requires TDRD3, which directly interacts with Top3beta and is present in animals but not bacteria or yeast. (PMID:27257063)
• Top3beta mutants lacking either its RNA-binding domain or catalytic residue fail to promote synapse formation, suggesting that Top3beta requires both its mRNA-binding and catalytic activity to facilitate neurodevelopment. (PMID:28039324)
• Structural basis of the interaction between TOP3B and the TDRD3 auxiliary factor has been reported. (PMID:28176834)
• Findings indicate the regulation of DNA topoisomerase III beta (TOP3B) activity by post-translational modification (PTM). (PMID:29471495)
• Results identified TOP3B gene deletion as candidate gene in the etiology of neurodevelopmental disorders including juvenile myoclonic epilepsy. (PMID:29490292)
• Our data show that TOP3B is necessary to prevent the accumulation of excessive R-loops and identify TOP3B as a putative cancer gene, and support recent data showing that R-loops are involved in cancer aetiology. (PMID:31795919)
• Further evidence of GABRA4 and TOP3B as autism susceptibility genes. (PMID:32028044)
• Topoisomerase III-beta is required for efficient replication of positive-sense RNA viruses. (PMID:32735900)
• DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks. (PMID:33378676)
• A dual-activity topoisomerase complex regulates mRNA translation and turnover. (PMID:35748872)
• Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3beta. (PMID:35945419)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	top3b	ENSDARG00000027586
mus_musculus	Top3b	ENSMUSG00000022779
rattus_norvegicus	Top3b	ENSRNOG00000001845
drosophila_melanogaster	Top3beta	FBGN0026015
caenorhabditis_elegans		WBGENE00012995

Paralogs (1): TOP3A (ENSG00000177302)

Protein

Protein identifiers

DNA topoisomerase 3-beta-1 — O95985 (reviewed: O95985)

Alternative names: DNA topoisomerase III beta-1

All UniProt accessions (12): O95985, C9J9X4, C9JEI7, C9JEQ1, C9JF56, C9JHR0, C9JKE2, C9JT00, C9JTQ7, F2Z2A5, H0Y6W0, H7C4B0

UniProt curated annotations — full annotation on UniProt →

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 target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5’-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3’-OH DNA strand. The free DNA strand than undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3’-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Possesses negatively supercoiled DNA relaxing activity.

Tissue specificity. Isoform 1 is found in testis, heart and skeletal muscle. A 4 kb transcript which probably represents isoform 2 is found in thymus, kidney and pancreas.

Similarity. Belongs to the type IA topoisomerase family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95985-1	1	yes
O95985-2	2
O95985-3	3

RefSeq proteins (9): NP_001269041, NP_001269042, NP_001336774, NP_001336776, NP_001336777, NP_001336779, NP_001336780, NP_001336781, NP_003926 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000380	Topo_IA	Family
IPR003601	Topo_IA_2	Domain
IPR003602	Topo_IA_DNA-bd_dom	Domain
IPR006171	TOPRIM_dom	Domain
IPR013497	Topo_IA_cen	Domain
IPR013824	Topo_IA_cen_sub1	Homologous_superfamily
IPR013825	Topo_IA_cen_sub2	Homologous_superfamily
IPR013826	Topo_IA_cen_sub3	Homologous_superfamily
IPR023405	Topo_IA_core_domain	Homologous_superfamily
IPR023406	Topo_IA_AS	Active_site
IPR034144	TOPRIM_TopoIII	Domain
IPR056452	Zn_ribbon_TOP3B	Domain

Pfam: PF01131, PF01751, PF23546

UniProt features (67 total): helix 27, strand 19, turn 10, splice variant 4, domain 2, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
5GVC	X-RAY DIFFRACTION	2.44
9CA4	ELECTRON MICROSCOPY	3.01
9CAK	ELECTRON MICROSCOPY	3.01
9CAL	ELECTRON MICROSCOPY	3.15
9CAH	ELECTRON MICROSCOPY	3.16
9CA1	ELECTRON MICROSCOPY	3.26
9CAG	ELECTRON MICROSCOPY	3.33
9C9Y	ELECTRON MICROSCOPY	3.35
9CA0	ELECTRON MICROSCOPY	3.48
9CAJ	ELECTRON MICROSCOPY	3.51
5GVE	X-RAY DIFFRACTION	3.61
9C9W	ELECTRON MICROSCOPY	4.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95985-F1	90.50	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 336 (o-(5’-phospho-dna)-tyrosine intermediate)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GOBP_CHROMOSOME_ORGANIZATION, HNF1_Q6, KAUFFMANN_DNA_REPAIR_GENES, KEGG_HOMOLOGOUS_RECOMBINATION, GOBP_DNA_CONFORMATION_CHANGE, GOBP_DNA_DAMAGE_RESPONSE, POU3F2_02, FAELT_B_CLL_WITH_VH3_21_UP, LEE_CALORIE_RESTRICTION_NEOCORTEX_DN, GAL_LEUKEMIC_STEM_CELL_UP, GOBP_CELL_CYCLE_PROCESS, GOBP_DNA_METABOLIC_PROCESS, MATZUK_MEIOTIC_AND_DNA_REPAIR, GOBP_DNA_REPAIR, GOBP_DNA_RECOMBINATION

GO Biological Process (4): DNA topological change (GO:0006265), DNA repair (GO:0006281), DNA recombination (GO:0006310), chromosome segregation (GO:0007059)

GO Molecular Function (7): DNA binding (GO:0003677), RNA binding (GO:0003723), DNA topoisomerase activity (GO:0003916), DNA topoisomerase type I (single strand cut, ATP-independent) activity (GO:0003917), RNA topoisomerase activity (GO:0140226), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (3): condensed chromosome (GO:0000793), nucleus (GO:0005634), DNA topoisomerase III-beta-TDRD3 complex (GO:0140225)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
nucleic acid binding	2
nucleic acid conformation isomerase activity	2
DNA conformation change	1
DNA damage response	1
cell cycle process	1
DNA binding	1
catalytic activity, acting on DNA	1
DNA topoisomerase activity	1
catalytic activity, acting on RNA	1
binding	1
catalytic activity	1
chromosome	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOP3B	TDRD3	Q9H7E2	929
TOP3B	TRIM41	Q8WV44	852
TOP3B	FXR2	P51116	677
TOP3B	PRY	O14603	669
TOP3B	TOP1	P11387	665
TOP3B	TOP2B	Q02880	617
TOP3B	RAD51	Q06609	611
TOP3B	RMI1	Q9H9A7	609
TOP3B	FMR1	Q06787	601
TOP3B	TOP1MT	Q969P6	577
TOP3B	TOP2A	P11388	572
TOP3B	TRIM27	P14373	548
TOP3B	TRIM45	Q9H8W5	547
TOP3B	MUS81	Q96NY9	518
TOP3B	BBOX1	O75936	511

IntAct

95 interactions, top by confidence:

A	B	Type	Score
TOP3B	MID2	psi-mi:“MI:0915”(physical association)	0.720
MID2	TOP3B	psi-mi:“MI:0915”(physical association)	0.720
SPRED2	TOP3B	psi-mi:“MI:0915”(physical association)	0.670
TRIM41	TOP3B	psi-mi:“MI:0915”(physical association)	0.670
SSX2IP	TOP3B	psi-mi:“MI:0915”(physical association)	0.670
TOP3B	SPRED2	psi-mi:“MI:0915”(physical association)	0.670
TOP3B	SSX2IP	psi-mi:“MI:0915”(physical association)	0.670
CIAO1	TOP3B	psi-mi:“MI:0915”(physical association)	0.670
TOP3B	TDRD3	psi-mi:“MI:0407”(direct interaction)	0.650
TOP3B	TDRD3	psi-mi:“MI:0914”(association)	0.640
TOP3B	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
PNMA2	TOP3B	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	TOP3B	psi-mi:“MI:0915”(physical association)	0.560
TOP3B	PNMA2	psi-mi:“MI:0915”(physical association)	0.560
TOP3B	GPRASP3	psi-mi:“MI:0915”(physical association)	0.560
TOP3B	ZNF250	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1626): PNMA2 (Two-hybrid), MID2 (Two-hybrid), ADAMTSL4 (Two-hybrid), TRIM41 (Two-hybrid), SSX2IP (Two-hybrid), SPRED2 (Two-hybrid), CHIC2 (Two-hybrid), KRTAP4-12 (Two-hybrid), TDRD3 (Co-fractionation), TOP3B (Proximity Label-MS), TOP3B (Affinity Capture-MS), TOP3B (Affinity Capture-MS), TOP3B (Affinity Capture-MS), TOP3B (Affinity Capture-MS), TOP3B (Affinity Capture-MS)

ESM2 similar proteins: A0A0L0P6P7, A4I2L4, A5PKR8, A8D8P8, A9U328, A9VB27, A9ZSZ2, D3TQJ5, F4IE66, F4ISQ7, O22899, O43143, O54747, O60126, O61660, O70157, O76922, O95985, O96651, P13099, P54358, P90829, P97283, Q07803, Q08BB1, Q0J0S6, Q13472, Q20875, Q22307, Q23223, Q4P1V1, Q5R9V1, Q5RAZ4, Q5RBD4, Q5XQC7, Q7K3M5, Q80VY9, Q8K0D5, Q8T2T7, Q96RP9

Diamond homologs: A0A0L0P6P7, C7J0A2, F4ISQ7, O60126, O61660, O70157, O73954, O95985, O96651, P13099, Q0J0S6, Q13472, Q8T2T7, Q9LVP1, Q9NG98, Q9Z321, O28469, Q9YB01, Q0VGT4, Q5HZL1, Q68G58, Q6DDT4, Q86YA3, Q8K203, Q8TAT5, Q9UBZ4, A8K979, Q5BKS4, Q5E9N9, Q6F598

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TOP3B	“form complex”	“TDRD3-TOP3B type IA topoisomerase complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Eukaryotic Translation Initiation	5	31.5×	6e-06
Cap-dependent Translation Initiation	5	31.5×	6e-06
SARS-CoV-1 modulates host translation machinery	5	31.5×	6e-06
Eukaryotic Translation Elongation	5	28.4×	1e-05
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	27.8×	1e-05
Formation of the ternary complex, and subsequently, the 43S complex	6	26.4×	3e-06
Nonsense-Mediated Decay (NMD)	5	23.8×	2e-05
Translation initiation complex formation	6	23.3×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	6	18.7×	2e-04
cytoplasmic translation	7	17.8×	6e-05
translation	7	9.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

177 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	125
Likely benign	19
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
997086	GRCh37/hg19 22q11.22(chr22:22313128-22556733)	Likely pathogenic

SpliceAI

3235 predictions. Top by Δscore:

Variant	Effect	Δscore
22:21958490:A:AC	donor_gain	1.0000
22:21958490:A:AT	donor_loss	1.0000
22:21958491:C:CC	donor_gain	1.0000
22:21958491:CCTTT:C	donor_gain	1.0000
22:21958689:TTGGC:T	acceptor_gain	1.0000
22:21958691:GGCCT:G	acceptor_loss	1.0000
22:21958692:GCCTG:G	acceptor_loss	1.0000
22:21958694:C:CC	acceptor_gain	1.0000
22:21958695:T:A	acceptor_loss	1.0000
22:21958698:G:T	acceptor_gain	1.0000
22:21958702:A:AC	acceptor_gain	1.0000
22:21959127:CCTA:C	donor_loss	1.0000
22:21959128:CTACC:C	donor_loss	1.0000
22:21959130:A:C	donor_loss	1.0000
22:21959131:C:CA	donor_loss	1.0000
22:21959230:TGC:T	acceptor_gain	1.0000
22:21959231:GCCTG:G	acceptor_loss	1.0000
22:21959232:CCTGC:C	acceptor_loss	1.0000
22:21959233:C:CA	acceptor_loss	1.0000
22:21959233:C:CC	acceptor_gain	1.0000
22:21959234:T:G	acceptor_loss	1.0000
22:21959582:TCTAC:T	donor_loss	1.0000
22:21959583:CTAC:C	donor_loss	1.0000
22:21959584:TA:T	donor_loss	1.0000
22:21959585:ACCAG:A	donor_loss	1.0000
22:21959586:CC:C	donor_loss	1.0000
22:21959617:T:TA	donor_gain	1.0000
22:21959618:C:A	donor_gain	1.0000
22:21959631:T:TA	donor_gain	1.0000
22:21959732:TGCAT:T	acceptor_gain	1.0000

AlphaMissense

5679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:21957461:A:G	C748R	1.000
22:21957563:A:G	C714R	1.000
22:21957578:A:G	C709R	1.000
22:21957587:A:G	C706R	1.000
22:21958526:G:C	C691W	1.000
22:21958528:A:G	C691R	1.000
22:21958537:A:G	C688R	1.000
22:21958603:A:G	C666R	1.000
22:21958672:A:G	C643R	1.000
22:21959167:A:G	C624R	1.000
22:21960354:C:G	G541R	1.000
22:21960404:C:G	R524P	1.000
22:21960426:G:C	H517D	1.000
22:21960436:G:C	S513R	1.000
22:21960436:G:T	S513R	1.000
22:21960438:T:G	S513R	1.000
22:21960440:G:T	A512D	1.000
22:21962445:C:A	M503I	1.000
22:21962445:C:G	M503I	1.000
22:21962445:C:T	M503I	1.000
22:21962458:A:G	L499P	1.000
22:21963961:G:T	P389H	1.000
22:21963966:A:C	H387Q	1.000
22:21963966:A:T	H387Q	1.000
22:21963968:G:C	H387D	1.000
22:21964253:A:G	Y336H	1.000
22:21964254:G:C	S335R	1.000
22:21964254:G:T	S335R	1.000
22:21964256:T:G	S335R	1.000
22:21964285:G:T	A325D	1.000

dbSNP variants (sampled 300 via entrez): RS1000062436 (22:21976663 C>T), RS1000094814 (22:21962095 CAG>C), RS1000106361 (22:21984388 G>A), RS1000233244 (22:21959254 G>A), RS1000239107 (22:21959776 G>A,C), RS1000288328 (22:21964445 C>G), RS1000349414 (22:21964705 G>A), RS1000419399 (22:21964574 C>G), RS1000487107 (22:21958217 C>G,T), RS1000527510 (22:21980063 C>T), RS1000560053 (22:21980281 C>T), RS1000585253 (22:21959533 T>C), RS1000791102 (22:21969142 T>A,C), RS1000909535 (22:21968443 C>T), RS1000990689 (22:21958036 T>C)

Disease associations

OMIM: gene MIM:603582 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003025_17	Attention function in attention deficit hyperactive disorder	6.000000e-06
GCST003801_1	Response to selective serotonin reuptake inhibitors in depression	5.000000e-07
GCST005169_3	Diastolic blood pressure	2.000000e-06
GCST008103_64	Bipolar disorder	6.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007636	attention function measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0006336	diastolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression, increases expression	1
potassium bromate	decreases expression	1
avobenzone	increases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Aspirin	increases expression	1
Benzo(a)pyrene	decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2ME	HAP1 TOP3B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

75 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists