Embryonal rhabdomyosarcoma

Summary

Embryonal rhabdomyosarcoma (MONDO:0009993) is a disease (an umbrella term covering 5 Mondo subtypes) with 2 cohort genes and 7 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous, dactinomycin, and vinorelbine.

At a glance

• Prevalence: <1 / 1 000 000 (Austria) [Orphanet-validated]
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 7

Clinical features

Epidemiology

Prevalence records

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

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.048	Austria	Validated
Annual incidence	<1 / 1 000 000	0.091	Belgium	Validated
Annual incidence	<1 / 1 000 000	0.034	Bulgaria	Validated
Annual incidence	<1 / 1 000 000	0.054	Croatia	Validated
Annual incidence	<1 / 1 000 000	0.011	Czech Republic	Validated
Annual incidence	<1 / 1 000 000	0.055	Estonia	Validated
Annual incidence	<1 / 1 000 000	0.005	Finland	Validated
Annual incidence	<1 / 1 000 000	0.046	Germany	Validated
Annual incidence	<1 / 1 000 000	0.089	Ireland	Validated
Annual incidence	<1 / 1 000 000	0.045	Italy	Validated
Annual incidence	<1 / 1 000 000	0.032	Latvia	Validated
Annual incidence	<1 / 1 000 000	0.046	Lithuania	Validated
Annual incidence	<1 / 1 000 000	0.057	Norway	Validated
Annual incidence	<1 / 1 000 000	0.035	Poland	Validated
Annual incidence	<1 / 1 000 000	0.051	Portugal	Validated
Annual incidence	<1 / 1 000 000	0.074	Slovakia	Validated
Annual incidence	<1 / 1 000 000	0.088	Slovenia	Validated
Annual incidence	<1 / 1 000 000	0.051	Spain	Validated
Annual incidence	<1 / 1 000 000	0.051	Switzerland	Validated
Annual incidence	<1 / 1 000 000	0.093	Netherlands	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	embryonal rhabdomyosarcoma
Mondo ID	MONDO:0009993
EFO	EFO:0000437
OMIM	268210
Orphanet	99757
DOID	DOID:3246
NCIT	C8971
SNOMED CT	404051002
UMLS	C0206656
MedGen	104910
GARD	0004702
MedDRA	10065868
Is cancer (heuristic)	no

Also known as: botryoid rhabdomyosarcoma (type of ERMS) · embryonal rhabdomyosarcoma · embryonal rhabdomyosarcoma (disease) · ERMS · rhabdomyosarcoma embryonal · rhabdomyosarcoma, embryonal, 1 · rhabdomyosarcoma, embryonal, type 1 · rhabdomyosarcoma, somatic · RMSE1 · spindle cell rhabdomyosarcomas (type of ERMS)

Data availability: 2 ClinVar variants · 1 HPO phenotype · 69 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › sarcoma › soft tissue sarcoma › rhabdomyosarcoma › embryonal rhabdomyosarcoma

Related subtypes (19): orbit rhabdomyosarcoma, spindle cell rhabdomyosarcoma, liver rhabdomyosarcoma, central nervous system rhabdomyosarcoma, mediastinum rhabdomyosarcoma, rectum rhabdomyosarcoma, gallbladder rhabdomyosarcoma, ovary rhabdomyosarcoma, breast rhabdomyosarcoma, testis rhabdomyosarcoma, rhabdomyosarcoma with mixed embryonal and alveolar features, prostate rhabdomyosarcoma, alveolar rhabdomyosarcoma, vaginal rhabdomyosarcoma, uterine corpus rhabdomyosarcoma, rhabdomyosarcoma of the cervix uteri, pleomorphic rhabdomyosarcoma, oral rhabdomyosarcoma, rhabdomyosarcoma, embryonal, 2

Subtypes (5): parameningeal embryonal rhabdomyosarcoma, prostate embryonal rhabdomyosarcoma, embryonal extrahepatic bile duct rhabdomyosarcoma, botryoid rhabdomyosarcoma, orbit embryonal rhabdomyosarcoma

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 conflicting classifications of pathogenicity, 1 other

ClinVar	Variant (HGVS)	Gene	Classification	Review
184046	NM_000455.5(STK11):c.1180G>A (p.Gly394Ser)	STK11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
40560	NM_002834.5(PTPN11):c.1508G>T (p.Gly503Val)	PTPN11	other	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STK11	Orphanet:2869	Peutz-Jeghers syndrome
PTPN11	Orphanet:2499	Metachondromatosis
PTPN11	Orphanet:500	Noonan syndrome with multiple lentigines
PTPN11	Orphanet:648	Noonan syndrome
PTPN11	Orphanet:86834	Juvenile myelomonocytic leukemia

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
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

Protein-family classification

Druggable: 2 · 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
Phosphatase	1	42.0×	0.047
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2

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
hindlimb stylopod muscle	1
left testis	1
right testis	1
dorsal motor nucleus of vagus nerve	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
PTPN11	295	ubiquitous	marker	medial globus pallidus, dorsal motor nucleus of vagus nerve, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPN11	6,009
STK11	5,146

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN11	Q06124	115
STK11	Q15831	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 66. 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
MET activates PTPN11	1	1142.0×	0.008	PTPN11
Co-inhibition by BTLA	1	1142.0×	0.008	PTPN11
STAT5 Activation	1	815.7×	0.008	PTPN11
AMPK inhibits chREBP transcriptional activation activity	1	713.8×	0.008	STK11
Netrin mediated repulsion signals	1	634.4×	0.008	PTPN11
MAPK1 (ERK2) activation	1	571.0×	0.008	PTPN11
STAT5 activation downstream of FLT3 ITD mutants	1	571.0×	0.008	PTPN11
MAPK3 (ERK1) activation	1	519.1×	0.008	PTPN11
Signaling by Leptin	1	519.1×	0.008	PTPN11
Interleukin-6 signaling	1	475.8×	0.008	PTPN11
Activated NTRK2 signals through FRS2 and FRS3	1	475.8×	0.008	PTPN11
PECAM1 interactions	1	439.2×	0.008	PTPN11
Regulation of IFNG signaling	1	407.9×	0.008	PTPN11
Prolactin receptor signaling	1	380.7×	0.008	PTPN11
Signaling by FLT3 ITD and TKD mutants	1	380.7×	0.008	PTPN11
Spry regulation of FGF signaling	1	356.9×	0.008	PTPN11
FOXO-mediated transcription of cell death genes	1	356.9×	0.008	STK11
Signal regulatory protein family interactions	1	335.9×	0.008	PTPN11
Platelet sensitization by LDL	1	335.9×	0.008	PTPN11
Regulation of RUNX1 Expression and Activity	1	335.9×	0.008	PTPN11
GAB1 signalosome	1	317.2×	0.008	PTPN11
PI-3K cascade:FGFR3	1	317.2×	0.008	PTPN11
Tie2 Signaling	1	300.5×	0.008	PTPN11
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	300.5×	0.008	PTPN11
PI-3K cascade:FGFR4	1	285.5×	0.008	PTPN11
Signaling by CSF3 (G-CSF)	1	285.5×	0.008	PTPN11
FRS-mediated FGFR3 signaling	1	271.9×	0.008	PTPN11
Co-inhibition by CTLA4	1	259.6×	0.008	PTPN11
Co-inhibition by PD-1	1	259.6×	0.008	PTPN11
PI-3K cascade:FGFR1	1	259.6×	0.008	PTPN11

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
negative regulation of cortisol secretion	1	8426.0×	0.002	PTPN11
negative regulation of growth hormone secretion	1	8426.0×	0.002	PTPN11
positive regulation of vesicle transport along microtubule	1	8426.0×	0.002	STK11
axonogenesis	2	160.5×	0.002	STK11, PTPN11
glucose homeostasis	2	130.6×	0.002	STK11, PTPN11
microvillus organization	1	4213.0×	0.003	PTPN11
intestinal epithelial cell migration	1	4213.0×	0.003	PTPN11
cerebellar cortex formation	1	2808.7×	0.004	PTPN11
regulation of type I interferon-mediated signaling pathway	1	2106.5×	0.005	PTPN11
ERBB signaling pathway	1	1685.2×	0.006	PTPN11
negative regulation of epithelial cell proliferation involved in prostate gland development	1	1404.3×	0.006	STK11
negative regulation of neutrophil activation	1	1203.7×	0.006	PTPN11
Golgi localization	1	1053.2×	0.006	STK11
epithelial cell proliferation involved in prostate gland development	1	1053.2×	0.006	STK11
positive regulation of hormone secretion	1	842.6×	0.006	PTPN11
genitalia development	1	842.6×	0.006	PTPN11
dendrite extension	1	842.6×	0.006	STK11
positive regulation of lipopolysaccharide-mediated signaling pathway	1	766.0×	0.006	PTPN11
activation of protein kinase activity	1	766.0×	0.006	STK11
atrioventricular canal development	1	766.0×	0.006	PTPN11
regulation of protein export from nucleus	1	766.0×	0.006	PTPN11
Bergmann glial cell differentiation	1	766.0×	0.006	PTPN11
positive thymic T cell selection	1	702.2×	0.006	STK11
G1 to G0 transition	1	702.2×	0.006	STK11
cellular response to UV-B	1	702.2×	0.006	STK11
negative regulation of cell adhesion mediated by integrin	1	648.1×	0.006	PTPN11
anoikis	1	648.1×	0.006	STK11
vasculature development	1	561.7×	0.006	STK11
neurotrophin TRK receptor signaling pathway	1	526.6×	0.006	PTPN11
positive regulation of ossification	1	468.1×	0.006	PTPN11

Therapeutics

Drugs indicated for this disease

0 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dactinomycin	Phase 3 (in late-stage trials)
Temsirolimus	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)
Vinorelbine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Etoposide, Ifosfamide, Temozolomide.

Drug target analysis

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

Druggability breadth: 2 of 2 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
STK11	FEDRATINIB
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STK11	17	4
PTPN11	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	STK11
MIDOSTAURIN	4	STK11
ESTRAMUSTINE PHOSPHATE	4	PTPN11
DINACICLIB	3	STK11
DOVITINIB	3	STK11
LESTAURTINIB	3	STK11
RUBOXISTAURIN	3	STK11
AZD-1480	2	STK11
SU-014813	2	STK11
R-406	2	STK11
TOZASERTIB	2	STK11
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
PF-00562271	1	STK11
KW-2449	1	STK11
PF-03758309	1	STK11
XL-228	1	STK11
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PTPN11	588	Binding:585, Functional:2, ADMET:1
STK11	244	Binding:244

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STK11	2.7.11.1	non-specific serine/threonine protein kinase
PTPN11	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
STK11	244
PTPN11	588

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).

Chemical tractability of cohort targets

25 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)
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	STK11
MIDOSTAURIN	4	STK11
ESTRAMUSTINE PHOSPHATE	4	PTPN11
DINACICLIB	3	STK11
DOVITINIB	3	STK11
LESTAURTINIB	3	STK11
RUBOXISTAURIN	3	STK11
AZD-1480	2	STK11
SU-014813	2	STK11
R-406	2	STK11
TOZASERTIB	2	STK11
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
PF-00562271	1	STK11
KW-2449	1	STK11
PF-03758309	1	STK11
XL-228	1	STK11
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	STK11, PTPN11
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	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: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	4
Not specified	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02567435	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT04994132	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
NCT05304585	PHASE3	RECRUITING	Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
NCT06669013	PHASE3	RECRUITING	Chemo-immunotherapy in Patients Under 18 Years of Age With Bone and Soft Tissue Sarcomas
NCT00923351	PHASE1/PHASE2	COMPLETED	Therapy to Treat Ewing’s Sarcoma, Rhabdomyosarcoma or Neuroblastoma
NCT03296371	Not specified	ACTIVE_NOT_RECRUITING	Genetic Mutational Analysis of Saliva or Buccal Mucosa Samples From Patients With Embryonal or Alveolar Rhabdomyosarcoma
NCT03382158	Not specified	RECRUITING	International PPB/DICER1 Registry

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
DACTINOMYCIN	4	3
VINORELBINE	4	2
DINUTUXIMAB BETA	4	1
IRINOTECAN HYDROCHLORIDE	4	1
TEMSIROLIMUS	4	1
CHEMBL4748391	0	3
CHEMBL541887	0	1