Ovarian disorder

Summary

Ovarian disorder (MONDO:0005558) is a disease (an umbrella term covering 11 Mondo subtypes) with 3 cohort genes and 30 clinical trials. Top therapeutic interventions include bevacizumab, niraparib, and temsirolimus.

At a glance

• Umbrella term: 11 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 3
• Clinical trials: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian disorder
Mondo ID	MONDO:0005558
EFO	EFO:0005771
MeSH	D010049
DOID	DOID:1100
NCIT	C26841
SNOMED CT	5552004
UMLS	C4021818
MedGen	892314
Anatomy (UBERON)	UBERON:0000992
Is cancer (heuristic)	no

Also known as: disease of ovary · disease or disorder of ovary · disorder of ovary · ovarian disease · ovarian disorder · ovary disease · ovary disease or disorder

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › ovarian disorder

Related subtypes (5): precocious puberty, disorder of sexual differentiation, hypogonadism, testicular disorder, gonadoblastoma

Subtypes (11): ovarian dysfunction, anovulation, ovarian cyst, ovarian stromal hyperthecosis, luteoma of pregnancy, ovarian endometriosis, oophoritis, ovarian hyperstimulation syndrome, ovarian neoplasm, ovarian remnant syndrome, ovarian ectopic pregnancy

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
37542	NM_007294.4(BRCA1):c.3700_3704del (p.Val1234fs)	BRCA1	Pathogenic	reviewed by expert panel
374000	NM_001282717.2(STAG3):c.2776C>T (p.Arg926Ter)	STAG3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
89552	NM_000179.3(MSH6):c.663A>C (p.Glu221Asp)	MSH6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
STAG3	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
STAG3	HGNC:11356	ENSG00000066923	Q9UJ98	Cohesin subunit SA-3	clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
STAG3	Cohesin subunit SA-3	Meiosis specific component of cohesin complex.
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
STAG3	Other/Unknown	no		STAG, ARM-type_fold, SCD
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
left testis	1
oocyte	1
right testis	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
STAG3	185	broad	marker	oocyte, right testis, left testis
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
MSH6	4,091
STAG3	1,232

Intra-cohort edges

A	B	Sources
BRCA1	MSH6	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRCA1	P38398	33
MSH6	P52701	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STAG3	Q9UJ98	78.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 64. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Diseases of DNA repair	2	380.7×	6e-04	BRCA1, MSH6
Meiosis	2	190.3×	0.001	BRCA1, STAG3
Reproduction	2	126.9×	0.002	BRCA1, STAG3
Meiotic synapsis	2	94.0×	0.002	BRCA1, STAG3
DNA Repair	2	65.6×	0.004	BRCA1, MSH6
Defective Mismatch Repair Associated With MSH6	1	1903.3×	0.004	MSH6
Defective DNA double strand break response due to BRCA1 loss of function	1	1903.3×	0.004	BRCA1
Defective DNA double strand break response due to BARD1 loss of function	1	1903.3×	0.004	BRCA1
Defective Mismatch Repair Associated With MSH2	1	1268.9×	0.006	MSH6
Mismatch Repair	1	951.7×	0.006	MSH6
Diseases of Mismatch Repair (MMR)	1	951.7×	0.006	MSH6
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	543.8×	0.010	BRCA1
Cell Cycle	2	24.0×	0.011	BRCA1, STAG3
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	317.2×	0.014	BRCA1
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	271.9×	0.014	MSH6
Diseases of DNA Double-Strand Break Repair	1	271.9×	0.014	BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	271.9×	0.014	BRCA1
Resolution of D-Loop Structures	1	211.5×	0.017	BRCA1
DNA Double Strand Break Response	1	158.6×	0.020	BRCA1
Impaired BRCA2 binding to PALB2	1	152.3×	0.020	BRCA1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	141.0×	0.020	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	141.0×	0.020	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	141.0×	0.020	BRCA1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	131.3×	0.020	BRCA1
Homologous DNA Pairing and Strand Exchange	1	126.9×	0.020	BRCA1
Homology Directed Repair	1	102.9×	0.020	BRCA1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	102.9×	0.020	BRCA1
Impaired BRCA2 binding to RAD51	1	102.9×	0.020	BRCA1
Metalloprotease DUBs	1	100.2×	0.020	BRCA1
Resolution of D-loop Structures through Holliday Junction Intermediates	1	100.2×	0.020	BRCA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intrinsic apoptotic signaling pathway in response to DNA damage	2	216.1×	0.002	BRCA1, MSH6
meiotic mismatch repair	1	5617.3×	0.005	MSH6
somatic recombination of immunoglobulin gene segments	1	1404.3×	0.008	MSH6
establishment of meiotic sister chromatid cohesion	1	1404.3×	0.008	STAG3
DNA repair	2	42.6×	0.008	BRCA1, MSH6
cellular response to indole-3-methanol	1	1123.5×	0.008	BRCA1
chordate embryonic development	1	936.2×	0.008	BRCA1
negative regulation of centriole replication	1	802.5×	0.009	BRCA1
DNA strand resection involved in replication fork processing	1	702.2×	0.009	BRCA1
DNA damage tolerance	1	561.7×	0.009	BRCA1
homologous recombination	1	468.1×	0.009	BRCA1
negative regulation of intracellular estrogen receptor signaling pathway	1	374.5×	0.009	BRCA1
negative regulation of DNA recombination	1	374.5×	0.009	MSH6
regulation of DNA damage checkpoint	1	374.5×	0.009	BRCA1
somatic hypermutation of immunoglobulin genes	1	351.1×	0.009	MSH6
negative regulation of gene expression via chromosomal CpG island methylation	1	351.1×	0.009	BRCA1
protein K6-linked ubiquitination	1	330.4×	0.009	BRCA1
random inactivation of X chromosome	1	312.1×	0.009	BRCA1
negative regulation of reactive oxygen species metabolic process	1	312.1×	0.009	BRCA1
negative regulation of fatty acid biosynthetic process	1	295.6×	0.009	BRCA1
isotype switching	1	280.9×	0.009	MSH6
mitotic G2/M transition checkpoint	1	267.5×	0.009	BRCA1
sister chromatid cohesion	1	255.3×	0.009	STAG3
mismatch repair	1	216.1×	0.010	MSH6
synaptonemal complex assembly	1	216.1×	0.010	STAG3
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	193.7×	0.011	BRCA1
positive regulation of vascular endothelial growth factor production	1	165.2×	0.012	BRCA1
mitotic G2 DNA damage checkpoint signaling	1	147.8×	0.013	BRCA1
determination of adult lifespan	1	144.0×	0.013	MSH6
response to ionizing radiation	1	137.0×	0.013	BRCA1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 1

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRCA1	RIBOFLAVIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA1	12	4
MSH6	1	2
STAG3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1
MOLIBRESIB	2	MSH6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BRCA1	13	Binding:9, Functional:4
MSH6	10	Binding:10

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

13 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1
MOLIBRESIB	2	MSH6

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BRCA1
B	Phased (≥1) drug, not yet approved	1	MSH6
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	STAG3

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
STAG3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 30.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	14
PHASE2	9
PHASE1	4
PHASE3	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01462890	PHASE3	COMPLETED	Evaluation of Optimal Treatment Duration of Bevacizumab Combination With Standard Chemotherapy in Patients With Ovarian Cancer
NCT04519151	PHASE2	RECRUITING	Pembrolizumab and Lenvatinib for Platinum- Sensitive Recurrent Ovarian Cancer
NCT04807166	PHASE2	ACTIVE_NOT_RECRUITING	Anlotinib Combined With Carboplatin/Paclitaxel as First-line Treatment in Patients With Advanced Ovarian Cancer
NCT05753826	PHASE2	RECRUITING	Adebrelimab Combined With Fuzuloparib in the Treatment of Patients With Recurrent Platinum-resistant Ovarian Cancer.
NCT00050414	PHASE2	COMPLETED	A Study of Trabectedin in Patients With Advanced Ovarian Cancer
NCT01310647	PHASE2	COMPLETED	Antral Follicle Priming Prior to ICSI (Intracytoplasmic Sperm Injection) in Previously Diagnosed Low Responders
NCT01460979	PHASE2	COMPLETED	Efficacy,Tolerability,Safety of Temsirolimus in Women With Platinum-refractory Ovarian Carcinoma or Advanced Endometrial Carcinoma
NCT03562897	PHASE2	COMPLETED	Evaluation of Ocoxin-Viusid® in Advanced or Metastatic Ovarian Epithelial Cancer
NCT04556071	PHASE2	UNKNOWN	Efficacy and Safety of Niraparib Combined With Bevacizumab in Platinum Refractory/Resistant Recurrent Ovarian Cancer
NCT04566952	PHASE2	UNKNOWN	Anlotinib Combined With Dose-reduced Olaparib in Patients With Platinum-Sensitive Recurrent Ovarian Cancer
NCT05001282	PHASE1/PHASE2	TERMINATED	A Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)
NCT05617755	PHASE1	ACTIVE_NOT_RECRUITING	AB-1015, an Integrated Circuit T (ICT) Cell Therapy in Patients With Platinum Resistant Epithelial Ovarian Cancer
NCT00816764	PHASE1	COMPLETED	A Phase 1 Study of the Safety and Pharmacokinetics of AGS-8M4 in Subjects With Advanced Ovarian Cancer
NCT01016054	PHASE1	TERMINATED	A Study of the Safety and Pharmacokinetics of AGS-8M4 Given in Combination With Chemotherapy in Women With Ovarian Cancer
NCT01832116	PHASE1	COMPLETED	89Zr-MMOT PET Imaging in Pancreatic and Ovarian Cancer Patients
NCT01292733	EARLY_PHASE1	TERMINATED	Cancer Screening Program for Women at High Risk for Developing Ovarian Cancer
NCT06750003	Not specified	NOT_YET_RECRUITING	4K Versus 3D Total Laparoscopic Bilateral Oophorectomy: Tools in Comparison
NCT06828419	Not specified	NOT_YET_RECRUITING	A Clinical Study on the Feasibility and Safety of Abdominal Endoscopic Single-port Surgery System to Assist Gynecological Day Surgery
NCT00210249	Not specified	COMPLETED	Development of an Evaluation Method of Elderly Condition in Patient Receiving Chemotherapy Treatment
NCT01566955	Not specified	COMPLETED	Feasability Study of Removing the Ovaries and Fallopian Tubes
NCT02973750	Not specified	COMPLETED	Determinants of Age-Related Treatment Effectiveness in Ovarian Cancer
NCT03150992	Not specified	UNKNOWN	EDMONd - Elemental Diet in Bowel Obstruction
NCT03593681	Not specified	COMPLETED	Compare Fallopian Tube Cells Collected by Cytuity With Removed Ovarian/Tubal Tissue to Determine Presence of Malignancy
NCT03897400	Not specified	COMPLETED	Ovarian Reserve in Crohn’s Disease
NCT04189406	Not specified	UNKNOWN	Turner Syndrome Minipuberty Study
NCT04209881	Not specified	COMPLETED	Ovarian Reserve and Ankylosing Spondylitis
NCT04579575	Not specified	UNKNOWN	Added Value of O-RADS in Evaluation of Ovarian Lesions
NCT04817449	Not specified	COMPLETED	Spectroscopy in Ovarian Cancer
NCT05048654	Not specified	WITHDRAWN	A Novel Ovarian Reserve Monitoring Algorithm for Patients at Risk of Ovarian Injury From Gonadotoxic Therapy
NCT05643599	Not specified	COMPLETED	The Relationship With Mad Honey Containing Grayanotoxin and Ovary Tissue

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BEVACIZUMAB	4	2
NIRAPARIB	4	1
TEMSIROLIMUS	4	1
TRABECTEDIN	4	1
ADEBRELIMAB	3	1
FLUZOPARIB	3	1
HONEY	3	1
PASIFOLATE EXATECAN	1	1
CHEMBL4746472	0	1