Germ cell tumor

Summary

Germ cell tumor (MONDO:0005040) is a cancer (an umbrella term covering 13 Mondo subtypes) with 1 cohort gene (1 CIViC-evidence somatic driver; 2 ClinVar predisposition records) and 81 clinical trials. Top therapeutic interventions include bleomycin, 2-mercaptoethanesulfonic acid, and brentuximab vedotin.

At a glance

• Classification: Cancer
• Umbrella term: 13 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 81

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	germ cell tumor
Mondo ID	MONDO:0005040
EFO	EFO:0000514
DOID	DOID:2994
NCIT	C3708
UMLS	C0205851
MedGen	60030
GARD	0013022
Is cancer (heuristic)	yes

Also known as: germ cell neoplasm · germ cell tumor · germ cells tumors · germ cells tumours · malignant tumour of the germ cell · neoplasm of germ cell · neoplasm of the germ cell · tumor of germ cell · tumor of the germ cell · tumour of germ cell · tumour of the germ cell

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 13 Mondo subtypes.

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

Related subtypes (47): pre-malignant neoplasm, endocrine gland neoplasm, giant cell tumor, hematopoietic and lymphoid system neoplasm, skin neoplasm, mesenchymal cell neoplasm, epidural spinal canal neoplasm, skeletal muscle neoplasm, trophoblastic neoplasm, cancer, benign neoplasm, upper aerodigestive tract neoplasm, histiocytoma, embryonal neoplasm, head and neck neoplasm, epithelial neoplasm, reproductive system neoplasm, non-seminomatous lesion, odontogenic cyst, phosphaturic mesenchymal tumor, thyroglossal duct cyst, hamartoma, mesenchymoma, mesothelial neoplasm, peritoneal neoplasm, virus associated tumor, nail tumor, respiratory tract neoplasm, spindle cell neoplasm, mixed neoplasm, urinary system neoplasm, cystic neoplasm, childhood neoplasm, melanocytic neoplasm, digestive system neoplasm, nervous system neoplasm, neoplasm of thorax, connective tissue neoplasm, bronchial adenomas/carcinoids childhood, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, erythroplakia, retroperitoneal neoplasm, cardiovascular neoplasm, dermoid or epidermoid cyst of the central nervous system, connective and soft tissue neoplasm, NTRK fusion positive cancer, RET fusion positive cancer

Subtypes (13): fallopian tube germ cell tumor, retroperitoneal germ cell neoplasm, childhood germ cell tumor, choriocarcinoma, malignant germ cell tumor, ovarian germ cell tumor, extragonadal germ cell tumor, gonadal germ cell tumor, germinomatous germ cell tumor, germ cell tumor of the vulva, nongerminomatous germ cell tumor, adult germ cell tumor, germ cell benign neoplasm

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:

1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
981808	NM_003579.4(RAD54L):c.604C>T (p.Arg202Cys)	RAD54L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2458243	NM_003579.4(RAD54L):c.281G>C (p.Gly94Ala)	RAD54L	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RAD54L			CIViC #6676

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAD54L	Orphanet:227535	Hereditary breast cancer

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RAD54L	HGNC:9826	ENSG00000085999	Q92698	DNA repair and recombination protein RAD54-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAD54L	DNA repair and recombination protein RAD54-like	Multifunctional ATPase that plays a role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAD54L	Enzyme (other)	yes	3.6.4.B9	SNF2_N, Helicase_C-like, Helicase_ATP-bd

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
left testis	1
right testis	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAD54L	173	ubiquitous	yes	left testis, right testis, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAD54L	2,927

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAD54L	Q92698	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
double-strand break repair via synthesis-dependent strand annealing	1	4213.0×	0.002	RAD54L
chromosome organization	1	581.1×	0.005	RAD54L
reciprocal meiotic recombination	1	561.7×	0.005	RAD54L
determination of adult lifespan	1	432.1×	0.005	RAD54L
response to ionizing radiation	1	411.0×	0.005	RAD54L
DNA recombination	1	337.0×	0.005	RAD54L
meiotic cell cycle	1	244.2×	0.006	RAD54L
double-strand break repair via homologous recombination	1	156.0×	0.008	RAD54L
response to xenobiotic stimulus	1	69.1×	0.016	RAD54L
DNA repair	1	63.8×	0.016	RAD54L

Therapeutics

Drugs indicated for this disease

0 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aprepitant	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bevacizumab, Bleomycin, Brentuximab Vedotin, Disulfiram, Durvalumab, Epirubicin, Erlotinib, Everolimus, Fludarabine, Gefitinib, Gemcitabine, Nivolumab, Olaparib, Oxaliplatin, Paclitaxel, Pazopanib, Sirolimus, Sunitinib, Tivantinib, Tremelimumab.

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAD54L	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
STREPTONIGRIN	2	RAD54L

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RAD54L	3	Functional:2, Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RAD54L	3.6.4.B9

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

1 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.

Compound	Max phase	Cohort target (bioactivity)
STREPTONIGRIN	2	RAD54L

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	1	RAD54L
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: 81.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	28
Not specified	24
PHASE1	16
PHASE1/PHASE2	7
PHASE3	5
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02375204	PHASE3	ACTIVE_NOT_RECRUITING	Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors
NCT02582697	PHASE3	RECRUITING	Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours
NCT03067181	PHASE3	RECRUITING	Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
NCT05874063	PHASE3	RECRUITING	Thromboprophylaxis in Good and Intermediate Prognosis Advanced Germ Cell Tumors
NCT00572572	PHASE3	COMPLETED	Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors
NCT06341998	PHASE2/PHASE3	COMPLETED	Clinical Study of Chemotherapy in the Treatment of Recurrent/Refractory Yolk Sac Tumor in Children
NCT01873326	PHASE2	ACTIVE_NOT_RECRUITING	Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors
NCT03158064	PHASE2	ACTIVE_NOT_RECRUITING	Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors
NCT04804007	PHASE2	RECRUITING	Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT
NCT04876456	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Trial of Cabozantinib With Patients With Refractory GCTs
NCT05092451	PHASE1/PHASE2	RECRUITING	Phase I/II Study of CAR.70- Engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Hematological Malignances
NCT06418789	PHASE2	RECRUITING	High-dose Chemotherapy as Second-line Drug Therapy for Relapsed Germ Cell Tumors
NCT06866964	PHASE2	RECRUITING	A Single-arm, Phase II Clinical Trial of ASPIRin to prEvent Venous Thromboembolism in Patients With Advanced Germ Cell Tumors Receiving Chemotherapy
NCT06937866	PHASE1/PHASE2	RECRUITING	Maintenance Zanzalintinib With Etoposide After HDCT in GCT
NCT07188441	PHASE2	RECRUITING	Treatment of Newly Diagnosed Central Malignant Germ Cell Tumor People With Teniposide Injection Combined With Cisplatin.
NCT00127049	PHASE2	UNKNOWN	Trial of Gemcitabine, Cisplatin, and Ifosfamide in Patients With Relapsed Non-Seminomatous Germ-Cell Tumors
NCT00179816	PHASE1/PHASE2	UNKNOWN	Tandem Peripheral Blood Stem Cell (PBSC) Rescue for High Risk Solid Tumors
NCT00183820	PHASE2	COMPLETED	Study of Gemcitabine, Oxaliplatin, and Paclitaxel in Patients With Refractory Germ Cell Carcinoma
NCT00187109	PHASE1/PHASE2	COMPLETED	Recombinant Human Thrombopoietin in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy
NCT00198172	PHASE2	TERMINATED	Phase II Study of Cisplatin Plus Epirubicin Salvage Chemo in Refractory Germ Cell Tumors
NCT00864318	PHASE2	COMPLETED	Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis
NCT00983398	PHASE1/PHASE2	UNKNOWN	Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors
NCT01466231	PHASE2	COMPLETED	Everolimus in Refractory Testicular Germ Cell Cancer
NCT01743482	PHASE2	COMPLETED	Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors
NCT01966913	PHASE1/PHASE2	UNKNOWN	Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors
NCT02161692	PHASE2	COMPLETED	Conventional Dose Versus High Dose Sequential Chemotherapy for Poor Prognosis Germ Cell Tumors
NCT02340884	PHASE2	COMPLETED	A Pilot RCT of the PRISM Intervention for AYAs With Cancer
NCT02414685	PHASE2	COMPLETED	First Line TIP in Poor Prognosis TGCTs.
NCT02499952	PHASE2	TERMINATED	Pembrolizumab in Subjects With Incurable Platinum-Refractory Germ Cell Tumors
NCT02624388	PHASE2	TERMINATED	Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)
NCT02689219	PHASE2	TERMINATED	Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
NCT02988843	PHASE2	TERMINATED	Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors
NCT03081923	PHASE2	TERMINATED	Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03726281	PHASE2	WITHDRAWN	Nivolumab in Platinum Recurrent or Refractory Metastatic Germ Cell Tumors
NCT03950830	PHASE2	COMPLETED	Disulfiram and Cisplatin in Refractory TGCTs.
NCT03960151	PHASE2	WITHDRAWN	Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy
NCT04648826	PHASE1/PHASE2	WITHDRAWN	Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies
NCT04791228	PHASE2	WITHDRAWN	A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors
NCT05634785	PHASE2	COMPLETED	CD30 CAR for CD30+ NSGCT

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BLEOMYCIN	4	5
2-MERCAPTOETHANESULFONIC ACID	4	2
BRENTUXIMAB VEDOTIN	4	2
TREMELIMUMAB	4	2
APREPITANT	4	1
DISULFIRAM	4	1
ETOPOSIDE PHOSPHATE	4	1
IFOSFAMIDE	4	1
MANNITOL	4	1
PALONOSETRON	4	1
PAZOPANIB	4	1
ROLAPITANT	4	1
SODIUM THIOSULFATE	4	1
SORBITOL	4	1
TENIPOSIDE	4	1
TETANUS TOXOID	4	1
URSODIOL	4	1
BINTRAFUSP ALFA	3	1
GUADECITABINE	3	1
KEYHOLE LIMPET HEMOCYANIN	3	1
RECOMBINANT HUMAN THROMBOPOIETIN	3	1
ZANZALINTINIB	3	1
GENISTEIN	2	1
CHEMBL3753202	0	1
CHEMBL4068768	0	1
CHEMBL4171277	0	1
CHEMBL5417591	0	1
CHEMBL4215501	0	1
CARBOPLATINE	0	1