Malignant germ cell tumor of ovary

Summary

Malignant germ cell tumor of ovary (MONDO:0018171) is a cancer with 2 cohort genes (1 CIViC-evidence somatic driver; 2 ClinVar predisposition records) and 1 clinical trial. Top therapeutic interventions include bleomycin and cisplatin.

At a glance

• Classification: Cancer
• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

26 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.08	Europe	Validated
Lifetime Prevalence	1-9 / 100 000	2.3	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.2	United States	Validated
Annual incidence	<1 / 1 000 000	0.072	Austria	Validated
Annual incidence	<1 / 1 000 000	0.07	Belgium	Validated
Annual incidence	<1 / 1 000 000	0.089	Bulgaria	Validated
Annual incidence	<1 / 1 000 000	0.093	Croatia	Validated
Annual incidence	<1 / 1 000 000	0.087	Czech Republic	Validated
Annual incidence	<1 / 1 000 000	0.062	Finland	Validated
Annual incidence	<1 / 1 000 000	0.065	Germany	Validated
Annual incidence	<1 / 1 000 000	0.085	Iceland	Validated
Annual incidence	<1 / 1 000 000	0.065	Ireland	Validated
Annual incidence	<1 / 1 000 000	0.065	Italy	Validated
Annual incidence	<1 / 1 000 000	0.081	Latvia	Validated
Annual incidence	<1 / 1 000 000	0.095	Lithuania	Validated
Annual incidence	<1 / 1 000 000	0.09	Norway	Validated
Annual incidence	<1 / 1 000 000	0.098	Poland	Validated
Annual incidence	<1 / 1 000 000	0.064	Portugal	Validated
Annual incidence	<1 / 1 000 000	0.075	Slovenia	Validated
Annual incidence	<1 / 1 000 000	0.072	Spain	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	malignant germ cell tumor of ovary
Mondo ID	MONDO:0018171
Orphanet	35807
DOID	DOID:2155
NCIT	C4514
SNOMED CT	254869000
UMLS	C0346180
MedGen	87544
GARD	0009330
Anatomy (UBERON)	UBERON:0000992
Is cancer (heuristic)	yes

Also known as: malignant germ cell neoplasm of ovary · malignant germ cell neoplasm of the ovary · malignant germ cell tumor of ovary · malignant germ cell tumor of the ovary · malignant germ cell tumour of the ovary · malignant ovarian germ cell neoplasm · malignant ovarian germ cell tumor · malignant ovarian germ cell tumour · MOGCT · ovarian germ cell cancer · ovary malignant germ cell tumor · ovary malignant germ cell tumour

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › malignant germ cell tumor › malignant germ cell tumor of ovary

Related subtypes (12): germinoma, seminoma, dysgerminoma, extragonadal germ cell cancer, pulmonary artery choriocarcinoma, malignant testicular germ cell tumor, malignant teratoma, malignant childhood germ cell neoplasm, mixed germ cell tumor, vaginal germ cell malignant tumor, malignant germ cell tumor of corpus uteri, malignant germ cell tumor of cervix uteri

Subtypes (4): ovarian primitive germ cell tumor, choriocarcinoma of ovary, primary non-gestational choriocarcinoma of ovary, malignant dysgerminomatous germ cell tumor of ovary

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
177959	NM_005188.4(CBL):c.1228-2A>G	CBL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
526381	NM_020937.4(FANCM):c.5791C>T (p.Arg1931Ter)	FANCM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CBL	LoF	ALL,AML,ESCA	CIViC #778

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CBL	Orphanet:363972	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
CBL	Orphanet:648	Noonan syndrome
CBL	Orphanet:86834	Juvenile myelomonocytic leukemia
CBL	Orphanet:98850	Aggressive systemic mastocytosis
FANCM	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
FANCM	Orphanet:84	Fanconi anemia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CBL	HGNC:1541	ENSG00000110395	P22681	E3 ubiquitin-protein ligase CBL	clinvar
FANCM	HGNC:23168	ENSG00000187790	Q8IYD8	Fanconi anemia group M protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CBL	E3 ubiquitin-protein ligase CBL	E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors.
FANCM	Fanconi anemia group M protein	DNA-dependent ATPase component of the Fanconi anemia (FA) core complex.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CBL	Transcription factor	no	2.3.2.27	Znf_RING, Adaptor_Cbl_N_hlx, UBA-like_sf
FANCM	Other/Unknown	no		Helicase_C-like, ERCC4_domain, RuvA_2-like

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
primordial germ cell in gonad	1
trigeminal ganglion	1
oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CBL	271	ubiquitous	marker	primordial germ cell in gonad, trigeminal ganglion, male germ line stem cell (sensu Vertebrata) in testis
FANCM	203	ubiquitous	marker	sperm, oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CBL	4,575
FANCM	2,764

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CBL	P22681	33
FANCM	Q8IYD8	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 53. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by EGFRvIII in Cancer	1	1142.0×	0.009	CBL
Signaling by Ligand-Responsive EGFR Variants in Cancer	1	951.7×	0.009	CBL
FLT3 signaling by CBL mutants	1	815.7×	0.009	CBL
Interleukin-6 family signaling	1	713.8×	0.009	CBL
PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1	1	634.4×	0.009	CBL
Signaling by EGFR in Cancer	1	571.0×	0.009	CBL
Signaling by FGFR3	1	571.0×	0.009	CBL
FLT3 signaling in disease	1	571.0×	0.009	CBL
Signaling by FGFR4	1	519.1×	0.009	CBL
Listeria monocytogenes entry into host cells	1	519.1×	0.009	CBL
Interleukin-6 signaling	1	475.8×	0.009	CBL
Signaling by FGFR1	1	407.9×	0.009	CBL
InlB-mediated entry of Listeria monocytogenes into host cell	1	380.7×	0.009	CBL
Spry regulation of FGF signaling	1	356.9×	0.009	CBL
Constitutive Signaling by EGFRvIII	1	356.9×	0.009	CBL
Negative regulation of FLT3	1	356.9×	0.009	CBL
Regulation of KIT signaling	1	300.5×	0.009	CBL
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	285.5×	0.009	CBL
Signaling by PTK6	1	271.9×	0.009	CBL
Signaling by Non-Receptor Tyrosine Kinases	1	271.9×	0.009	CBL
Negative regulation of MET activity	1	259.6×	0.009	CBL
Regulation of signaling by CBL	1	248.3×	0.009	CBL
Negative regulation of FGFR3 signaling	1	219.6×	0.009	CBL
Negative regulation of FGFR4 signaling	1	203.9×	0.009	CBL
Signaling by FGFR2	1	203.9×	0.009	CBL
Negative regulation of FGFR1 signaling	1	184.2×	0.009	CBL
Negative regulation of FGFR2 signaling	1	184.2×	0.009	CBL
EGFR downregulation	1	173.0×	0.009	CBL
Signaling by FGFR	1	173.0×	0.009	CBL
FLT3 Signaling	1	173.0×	0.009	CBL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of platelet-derived growth factor receptor-alpha signaling pathway	1	2808.7×	0.005	CBL
regulation of Rap protein signal transduction	1	2106.5×	0.005	CBL
double-strand break repair via synthesis-dependent strand annealing	1	2106.5×	0.005	FANCM
positive regulation of protein monoubiquitination	1	1685.2×	0.005	FANCM
ubiquitin-dependent endocytosis	1	936.2×	0.007	CBL
resolution of meiotic recombination intermediates	1	468.1×	0.009	FANCM
positive regulation of receptor-mediated endocytosis	1	401.2×	0.009	CBL
negative regulation of epidermal growth factor receptor signaling pathway	1	383.0×	0.009	CBL
cellular response to platelet-derived growth factor stimulus	1	324.1×	0.009	CBL
mast cell degranulation	1	312.1×	0.009	CBL
response to gamma radiation	1	290.6×	0.009	CBL
negative regulation of T cell activation	1	263.3×	0.009	CBL
positive regulation of epidermal growth factor receptor signaling pathway	1	247.8×	0.009	CBL
response to testosterone	1	234.1×	0.009	CBL
response to starvation	1	234.1×	0.009	CBL
cellular response to nerve growth factor stimulus	1	234.1×	0.009	CBL
interstrand cross-link repair	1	216.1×	0.009	FANCM
replication fork processing	1	210.7×	0.009	FANCM
symbiont entry into host cell	1	200.6×	0.009	CBL
negative regulation of T cell receptor signaling pathway	1	183.2×	0.010	CBL
protein monoubiquitination	1	172.0×	0.010	CBL
response to activity	1	162.0×	0.010	CBL
protein K63-linked ubiquitination	1	133.8×	0.011	CBL
protein autoubiquitination	1	117.0×	0.012	CBL
male gonad development	1	78.0×	0.018	CBL
response to ethanol	1	73.3×	0.018	CBL
cytokine-mediated signaling pathway	1	65.3×	0.020	CBL
cellular response to hypoxia	1	60.6×	0.021	CBL
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	39.2×	0.031	CBL
ubiquitin-dependent protein catabolic process	1	37.1×	0.031	CBL

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CBL	0	0
FANCM	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CBL	4	Binding:2, Toxicity:2

Cohort enzymes (BRENDA EC)

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	CBL, FANCM

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CBL	4	—
FANCM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02429687	PHASE3	RECRUITING	TC or BEP in Treating Patients With Malignant Ovarian Germ Cell Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BLEOMYCIN	4	1
CISPLATIN	4	1