Dysgerminoma

Summary

Dysgerminoma (MONDO:0003002) is a disease with 3 cohort genes and 2 clinical trials. Top therapeutic interventions include darbepoetin alfa and tremelimumab.

At a glance

• Cohort genes: 3
• ClinVar variants: 5
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dysgerminoma
Mondo ID	MONDO:0003002
MeSH	D004407
DOID	DOID:4441
ICD-11	817547820
NCIT	C2996
UMLS	C0013377
MedGen	41680
GARD	0023323
Is cancer (heuristic)	no

Also known as: dysgerminoma · dysgerminoma (disease) · dysgerminoma, malignant

Data availability: 5 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 2 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 › dysgerminoma

Related subtypes (12): germinoma, seminoma, 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, malignant germ cell tumor of ovary

Subtypes (2): pineal region dysgerminoma, dysgerminoma 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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 other, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
37417	NM_007294.4(BRCA1):c.1504_1508del (p.Leu502fs)	BRCA1	Pathogenic	reviewed by expert panel
13863	NM_000222.3(KIT):c.2446G>C (p.Asp816His)	KIT	Pathogenic	criteria provided, multiple submitters, no conflicts
13852	NM_000222.3(KIT):c.2447A>T (p.Asp816Val)	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
438769	NM_000222.3(KIT):c.2851_2852dup (p.Val951_Asp952insTer)	KIT	other	no assertion criteria provided
438789	NM_003011.4(SET):c.777dup (p.Asp260fs)	SET	other	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 29 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SET	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SET	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
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
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans
KIT	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
KIT	Orphanet:98834	Acute myeloblastic leukemia with maturation
KIT	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm

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
SET	HGNC:10760	ENSG00000119335	Q01105	Protein SET	clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SET	Protein SET	Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning.
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.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.313
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SET	Other/Unknown	no		NAP, NAP-like_sf
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS

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
calcaneal tendon	1
endometrium epithelium	1
ganglionic eminence	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
ventricular zone	1
lateral nuclear group of thalamus	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SET	295	ubiquitous	marker	ganglionic eminence, endometrium epithelium, calcaneal tendon
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
KIT	6,087
SET	2,822

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIT	P10721	52
BRCA1	P38398	33
SET	Q01105	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 99. 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
Dasatinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Imatinib-resistant KIT mutants	1	3806.7×	0.002	KIT
KIT mutants bind TKIs	1	3806.7×	0.002	KIT
Masitinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Nilotinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Regorafenib-resistant KIT mutants	1	3806.7×	0.002	KIT
Signaling by kinase domain mutants of KIT	1	3806.7×	0.002	KIT
Sunitinib-resistant KIT mutants	1	3806.7×	0.002	KIT
Signaling by juxtamembrane domain KIT mutants	1	3806.7×	0.002	KIT
Sorafenib-resistant KIT mutants	1	3806.7×	0.002	KIT
Drug resistance of KIT mutants	1	3806.7×	0.002	KIT
Signaling by extracellular domain mutants of KIT	1	3806.7×	0.002	KIT
MITF-M-regulated melanocyte development	2	76.1×	0.002	BRCA1, KIT
Defective DNA double strand break response due to BRCA1 loss of function	1	1903.3×	0.003	BRCA1
Defective DNA double strand break response due to BARD1 loss of function	1	1903.3×	0.003	BRCA1
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	543.8×	0.011	BRCA1
HuR (ELAVL1) binds and stabilizes mRNA	1	423.0×	0.013	SET
Cell Cycle	2	24.0×	0.013	SET, BRCA1
Signaling by KIT in disease	1	380.7×	0.014	KIT
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	317.2×	0.016	BRCA1
Diseases of DNA Double-Strand Break Repair	1	271.9×	0.016	BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	271.9×	0.016	BRCA1
Regulation of mRNA stability by proteins that bind AU-rich elements	1	253.8×	0.016	SET
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	253.8×	0.016	KIT
Resolution of D-Loop Structures	1	211.5×	0.017	BRCA1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	211.5×	0.017	KIT
Developmental Lineage of Mammary Gland Alveolar Cells	1	211.5×	0.017	KIT
Regulation of KIT signaling	1	200.3×	0.018	KIT
Diseases of DNA repair	1	190.3×	0.018	BRCA1
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	173.0×	0.018	KIT

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
melanocyte adhesion	1	5617.3×	0.006	KIT
positive regulation of pyloric antrum smooth muscle contraction	1	5617.3×	0.006	KIT
positive regulation of colon smooth muscle contraction	1	5617.3×	0.006	KIT
positive regulation of vascular associated smooth muscle cell differentiation	1	2808.7×	0.006	KIT
Fc receptor signaling pathway	1	1872.4×	0.006	KIT
Kit signaling pathway	1	1872.4×	0.006	KIT
melanocyte migration	1	1872.4×	0.006	KIT
obsolete regulation of bile acid metabolic process	1	1872.4×	0.006	KIT
positive regulation of small intestine smooth muscle contraction	1	1872.4×	0.006	KIT
mast cell chemotaxis	1	1404.3×	0.006	KIT
hematopoietic stem cell migration	1	1404.3×	0.006	KIT
mast cell differentiation	1	1404.3×	0.006	KIT
positive regulation of dendritic cell cytokine production	1	1123.5×	0.006	KIT
positive regulation of mast cell cytokine production	1	1123.5×	0.006	KIT
mast cell proliferation	1	1123.5×	0.006	KIT
positive regulation of mast cell proliferation	1	1123.5×	0.006	KIT
cellular response to indole-3-methanol	1	1123.5×	0.006	BRCA1
lymphoid progenitor cell differentiation	1	936.2×	0.006	KIT
erythropoietin-mediated signaling pathway	1	936.2×	0.006	KIT
chordate embryonic development	1	936.2×	0.006	BRCA1
myeloid progenitor cell differentiation	1	802.5×	0.006	KIT
immature B cell differentiation	1	802.5×	0.006	KIT
glycosphingolipid metabolic process	1	802.5×	0.006	KIT
negative regulation of centriole replication	1	802.5×	0.006	BRCA1
tongue development	1	702.2×	0.006	KIT
DNA strand resection involved in replication fork processing	1	702.2×	0.006	BRCA1
primordial germ cell migration	1	624.1×	0.006	KIT
positive regulation of long-term neuronal synaptic plasticity	1	624.1×	0.006	KIT
negative regulation of developmental process	1	624.1×	0.006	KIT
DNA damage tolerance	1	561.7×	0.007	BRCA1

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Darbepoetin Alfa, Durvalumab, Tremelimumab.

Drug target analysis

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

Druggability breadth: 3 of 3 evidence-associated genes (100%) 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
KIT	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KIT	99	4
BRCA1	12	4
SET	1	2

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
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
BRCA1	13	Binding:9, Functional:4
SET	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
KIT	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
KIT	2,305

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

30 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
PONATINIB	4	KIT
FEDRATINIB	4	KIT
TIVOZANIB	4	KIT
LENVATINIB	4	KIT
AXITINIB	4	KIT
SORAFENIB	4	KIT
DASATINIB ANHYDROUS	4	KIT
NICLOSAMIDE	4	KIT
IMATINIB MESYLATE	4	KIT
RUXOLITINIB	4	KIT
INFIGRATINIB PHOSPHATE	4	KIT
INFIGRATINIB	4	KIT
REGORAFENIB	4	KIT
ENTRECTINIB	4	KIT
CABOZANTINIB	4	KIT
CERITINIB	4	KIT
VANDETANIB	4	KIT
NILOTINIB	4	KIT
BOSUTINIB	4	KIT
BRIGATINIB	4	KIT
PEXIDARTINIB	4	KIT
AVAPRITINIB	4	KIT
RIPRETINIB	4	KIT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BRCA1, KIT
B	Phased (≥1) drug, not yet approved	1	SET
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03158064	PHASE2	ACTIVE_NOT_RECRUITING	Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors
NCT00204633	PHASE2	COMPLETED	Darbepoetin Alfa in Patients With Poor Prognosis Germ Cell Tumor Treated With High-Dose Chemotherapy (HD-VIP)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DARBEPOETIN ALFA	4	1
TREMELIMUMAB	4	1