Atypical teratoid rhabdoid tumor

Summary

Atypical teratoid rhabdoid tumor (MONDO:0020560) is a cancer with 5 cohort genes (5 CIViC-evidence somatic drivers; 3 ClinVar predisposition records) and 31 clinical trials. Molecularly, SMARCB1 Loss confers sensitivity to Tazemetostat in Atypical Teratoid Rhabdoid Tumor (CIViC Level B). Top therapeutic interventions include celecoxib, etoposide phosphate, and tazemetostat.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Austria) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 3
• Phenotypes (HPO): 16
• Clinical trials: 31
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	1.38	Austria	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000737	Irritability	Very frequent (80-99%)
HP:0000741	Apathy	Very frequent (80-99%)
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0100836	Malignant neoplasm of the central nervous system	Very frequent (80-99%)
HP:0000238	Hydrocephalus	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001376	Limitation of joint mobility	Frequent (30-79%)
HP:0002076	Migraine	Frequent (30-79%)
HP:0004372	Reduced consciousness/confusion	Frequent (30-79%)
HP:0004374	Hemiplegia/hemiparesis	Frequent (30-79%)
HP:0002514	Cerebral calcification	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0100021	Cerebral palsy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	atypical teratoid rhabdoid tumor
Mondo ID	MONDO:0020560
EFO	EFO:1002008
Orphanet	99966
DOID	DOID:2129
NCIT	C6906
UMLS	C1266184
MedGen	226853
GARD	0016926
Anatomy (UBERON)	UBERON:0001017
Is cancer (heuristic)	yes

Also known as: AT/RT · ATRT · ATT/RHT · atypical teratoid/rhabdoid tumor · atypical teratoid/rhabdoid tumor (morphologic abnormality) · atypical teratoid/rhabdoid tumor (WHO grade IV) · atypical teratoid/rhabdoid tumour (morphologic abnormality) · atypical teratoid/rhabdoid tumour (WHO grade IV) · central nervous system rhabdoid neoplasm · central nervous system rhabdoid tumor · central nervous system rhabdoid tumour · CNS rhabdoid neoplasm · CNS rhabdoid tumor · CNS rhabdoid tumour · malignant brain rhabdoid neoplasm · malignant brain rhabdoid tumor · malignant brain rhabdoid tumour · malignant rhabdoid neoplasm of brain · malignant rhabdoid neoplasm of the brain · malignant rhabdoid tumor of brain (+24 more)

Data availability: 3 ClinVar variants · 15 cell lines · 1 intOGen driver record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › nervous system cancer › central nervous system cancer › central nervous system sarcoma › atypical teratoid rhabdoid tumor

Related subtypes (11): spinal cord sarcoma, brain sarcoma, central nervous system rhabdomyosarcoma, central nervous system angiosarcoma, central nervous system leiomyosarcoma, central nervous system fibrosarcoma, meningeal sarcoma, intracranial extraskeletal myxoid chondrosarcoma, central nervous system extraskeletal osteosarcoma, malignant peripheral nerve sheath tumor, isolated melanotic schwannoma

Subtypes (1): rhabdoid tumor predisposition syndrome 2

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 benign/likely benign, 1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
12365	NM_000546.6(TP53):c.733G>A (p.Gly245Ser)	TP53	Pathogenic	reviewed by expert panel
620616	NM_000059.4(BRCA2):c.9503_9506delinsTAAG (p.Asn3168_Ile3169delinsIleSer)	BRCA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
11724	NM_000489.6(ATRX):c.5579A>G (p.Asn1860Ser)	ATRX	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 46 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78
SMARCB1	Act	ATRT,MBL,NBL,PANET,PAST	CIViC #5356
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
ATRX	LoF	ACC,CLLSLL,GB,GBM,HGGNOS,LGGNOS,LMS,NBL,OS,OVT,PANET,PAST,SARCNOS,SOFT_TISSUE	CIViC #525

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
SMARCB1	Orphanet:1465	Coffin-Siris syndrome
SMARCB1	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCB1	Orphanet:2495	Meningioma
SMARCB1	Orphanet:263662	Familial multiple meningioma
SMARCB1	Orphanet:93921	Full schwannomatosis
SMARCB1	Orphanet:99966	Atypical teratoid rhabdoid tumor
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
ATRX	Orphanet:100075	Neuroendocrine tumor of stomach
ATRX	Orphanet:231401	Alpha-thalassemia-myelodysplastic syndrome
ATRX	Orphanet:847	X-linked alpha-thalassemia-intellectual disability syndrome
ATRX	Orphanet:96253	Cushing disease

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	civic_evidence
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
ATRX	HGNC:886	ENSG00000085224	P46100	Transcriptional regulator ATRX	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
ATRX	Transcriptional regulator ATRX	Involved in transcriptional regulation and chromatin remodeling.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 3 · 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	2	3.3×	0.229
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
ATRX	Transcription factor	no		SNF2_N, Helicase_C-like, Znf_FYVE_PHD

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	3
cortical plate	2
ventricular zone	2
cervix squamous epithelium	1
embryo	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1
tendon of biceps brachii	1
calcaneal tendon	1
colonic epithelium	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
ATRX	294	ubiquitous	marker	endothelial cell, calcaneal tendon, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
SMARCA4	8,138
ATRX	5,796
SMARCB1	5,083
BRCA2	4,839

Intra-cohort edges

A	B	Sources
ATRX	BRCA2	string_interaction
ATRX	TP53	string_interaction
BRCA2	TP53	string_interaction
SMARCA4	SMARCB1	intact, string_interaction
SMARCB1	TP53	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
SMARCA4	P51532	31
SMARCB1	Q12824	17
BRCA2	P51587	14
ATRX	P46100	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 114. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the canonical BAF (cBAF) complex	2	253.8×	1e-03	SMARCA4, SMARCB1
Formation of the polybromo-BAF (pBAF) complex	2	253.8×	1e-03	SMARCA4, SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	2	240.4×	1e-03	SMARCA4, SMARCB1
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	2	182.7×	0.001	SMARCA4, SMARCB1
Regulation of endogenous retroelements	2	147.3×	0.002	SMARCA4, SMARCB1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	2	120.2×	0.002	SMARCA4, SMARCB1
Regulation of MITF-M-dependent genes involved in pigmentation	2	106.2×	0.002	SMARCA4, SMARCB1
Alternative Lengthening of Telomeres (ALT)	1	2284.0×	0.004	ATRX
Defective Inhibition of DNA Recombination at Telomere	1	2284.0×	0.004	ATRX
Diseases of Telomere Maintenance	1	2284.0×	0.004	ATRX
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	2284.0×	0.004	TP53
MITF-M-dependent gene expression	2	72.5×	0.004	SMARCA4, SMARCB1
RMTs methylate histone arginines	2	58.6×	0.004	SMARCA4, SMARCB1
Transcriptional regulation by RUNX1	2	58.6×	0.004	SMARCA4, SMARCB1
Regulation of TP53 Expression	1	1142.0×	0.005	TP53
Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations	1	1142.0×	0.005	ATRX
Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations	1	1142.0×	0.005	ATRX
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	2	47.1×	0.005	SMARCA4, SMARCB1
MITF-M-regulated melanocyte development	2	45.7×	0.005	SMARCA4, SMARCB1
Impaired BRCA2 translocation to the nucleus	1	761.3×	0.007	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	761.3×	0.007	BRCA2
Chromatin organization	2	32.6×	0.008	SMARCA4, SMARCB1
Transcriptional activation of cell cycle inhibitor p21	1	571.0×	0.009	TP53
Chromatin modifying enzymes	2	28.9×	0.009	SMARCA4, SMARCB1
Epigenetic regulation of gene expression	2	28.6×	0.009	SMARCA4, SMARCB1
Activation of NOXA and translocation to mitochondria	1	380.7×	0.012	TP53
RUNX3 regulates CDKN1A transcription	1	326.3×	0.013	TP53
PI5P Regulates TP53 Acetylation	1	253.8×	0.016	TP53
Activation of PUMA and translocation to mitochondria	1	228.4×	0.017	TP53
TP53 Regulates Transcription of Caspase Activators and Caspases	1	190.3×	0.019	TP53

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of glucose mediated signaling pathway	2	2246.9×	1e-05	SMARCA4, SMARCB1
transcription initiation-coupled chromatin remodeling	3	229.8×	1e-05	SMARCA4, SMARCB1, TP53
DNA damage response, signal transduction by p53 class mediator	3	215.1×	1e-05	BRCA2, TP53, ATRX
RNA polymerase I preinitiation complex assembly	2	1348.2×	3e-05	SMARCA4, SMARCB1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	2	612.8×	1e-04	SMARCA4, SMARCB1
response to X-ray	2	354.8×	3e-04	BRCA2, TP53
host-mediated activation of viral transcription	2	354.8×	3e-04	SMARCA4, SMARCB1
nucleosome disassembly	2	321.0×	3e-04	SMARCA4, SMARCB1
regulation of G0 to G1 transition	2	269.6×	4e-04	SMARCA4, SMARCB1
regulation of nucleotide-excision repair	2	240.7×	4e-04	SMARCA4, SMARCB1
response to gamma radiation	2	232.4×	4e-04	BRCA2, TP53
chromatin remodeling	3	43.8×	4e-04	SMARCA4, SMARCB1, ATRX
regulation of mitotic metaphase/anaphase transition	2	198.3×	5e-04	SMARCA4, SMARCB1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	2	198.3×	5e-04	BRCA2, TP53
positive regulation of T cell differentiation	2	182.2×	6e-04	SMARCA4, SMARCB1
cellular response to ionizing radiation	2	164.4×	7e-04	BRCA2, TP53
nucleotide-excision repair	2	153.2×	7e-04	BRCA2, TP53
positive regulation of myoblast differentiation	2	146.5×	7e-04	SMARCA4, SMARCB1
positive regulation of stem cell population maintenance	2	137.6×	7e-04	SMARCA4, SMARCB1
positive regulation of double-strand break repair	2	137.6×	7e-04	SMARCA4, SMARCB1
positive regulation of transcription by RNA polymerase II	4	11.9×	8e-04	SMARCA4, SMARCB1, TP53, ATRX
regulation of G1/S transition of mitotic cell cycle	2	122.6×	9e-04	SMARCA4, SMARCB1
cellular senescence	2	118.3×	9e-04	BRCA2, TP53
positive regulation of miRNA transcription	2	116.2×	9e-04	SMARCA4, TP53
positive regulation of cell differentiation	2	107.0×	1e-03	SMARCA4, SMARCB1
double-strand break repair	2	81.2×	0.002	BRCA2, TP53
single stranded viral RNA replication via double stranded DNA intermediate	1	3370.4×	0.002	SMARCB1
negative regulation of helicase activity	1	3370.4×	0.002	TP53
cellular response to actinomycin D	1	3370.4×	0.002	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	3370.4×	0.002	TP53

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
TP53	NITROFURANTOIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
SMARCA4	2	2
SMARCB1	0	0
BRCA2	0	0
ATRX	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
SMARCA4	230	Binding:207, ADMET:12, Functional:11
SMARCB1	7	Binding:7

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMARCA4	230
TP53	869

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TP53
B	Phased (≥1) drug, not yet approved	1	SMARCA4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	SMARCB1, BRCA2, ATRX

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SMARCB1	7	SMARCA4
BRCA2	0	—
ATRX	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 31.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	14
PHASE2	6
Not specified	6
PHASE1/PHASE2	3
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT02114229	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Study of Alisertib Therapy for Rhabdoid Tumors
NCT04416568	PHASE2	ACTIVE_NOT_RECRUITING	Study of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers
NCT05286801	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
NCT05407441	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Tazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors
NCT06465199	PHASE1/PHASE2	RECRUITING	Eflornithine (DFMO) and AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas
NCT07447076	PHASE2	NOT_YET_RECRUITING	Study of Novel Therapies for Young People With Recurrent/Progressive Atypical Teratoid Rhabdoid Tumor (ATRT)
NCT00003469	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Children With Rhabdoid Tumor of the Central Nervous System
NCT04897880	PHASE2	TERMINATED	A Study of Panobinostat in Pediatric Patients With Solid Tumors Including MRT/ATRT
NCT03500991	PHASE1	ACTIVE_NOT_RECRUITING	HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors
NCT04185038	PHASE1	RECRUITING	Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors
NCT05835687	PHASE1	RECRUITING	Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors
NCT06193759	PHASE1	RECRUITING	Immunotherapy for Malignant Pediatric Brain Tumors Employing Adoptive Cellular Therapy (IMPACT)
NCT07390539	PHASE1	NOT_YET_RECRUITING	B7-H3.CD28Z.CART in CNS Neoplasms
NCT07513194	PHASE1	NOT_YET_RECRUITING	GPC3 CAR T Cells With IL-15 and IL-21 for Recurrent ATRT and CNS Rhabdoid Tumors (RADIANT)
NCT07584499	PHASE1	RECRUITING	Phase I Study of Becotatug Vedotin for Safety and Efficacy in EGFR-Positive Pediatric Relapsed/Refractory or Metastatic Solid Tumors
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT02962167	PHASE1	COMPLETED	Modified Measles Virus (MV-NIS) for Children and Young Adults With Recurrent Medulloblastoma or Recurrent ATRT
NCT03387020	PHASE1	COMPLETED	Ribociclib and Everolimus in Treating Children With Recurrent or Refractory Malignant Brain Tumors
NCT03434262	PHASE1	COMPLETED	SJDAWN: St. Jude Children’s Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors
NCT03638167	PHASE1	COMPLETED	EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors
NCT04521946	PHASE1	WITHDRAWN	Chemotherapy and Donor Stem Transplant for the Treatment of Patients With High Grade Brain Cancer
NCT05952687	PHASE1	WITHDRAWN	Trial of Idasanutlin and Selinexor Therapy for Children With Progressive/Relapsed AT/RT or Extra-CNS Malignant Rhabdoid Tumors
NCT06942039	EARLY_PHASE1	RECRUITING	Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation
NCT07017816	EARLY_PHASE1	RECRUITING	A Phase 0/1 Study of cDNA for TP53, Checkpoint Inhibition and Radiation in Children With Recurrent, Progressive or Refractory CNS Malignancies.
NCT07589361	Not specified	NOT_YET_RECRUITING	Safety and Efficacy of Vertebral Body-Sparing Craniospinal Irradiation With Proton Therapy in Pediatric Tumors
NCT01505569	Not specified	COMPLETED	Auto Transplant for High Risk or Relapsed Solid or CNS Tumors
NCT03874455	Not specified	NO_LONGER_AVAILABLE	Tazemetostat Expanded Access Program for Adults With Solid Tumors
NCT04868799	Not specified	COMPLETED	Finding New Targets by Proteomic Approaches (InnovRT1)
NCT04987476	Not specified	COMPLETED	Rhabdoid Tumors Cellular Architecture by Single-cell Analyses (InnovRT-2)
NCT05934630	Not specified	TERMINATED	Testing Cerebrospinal Fluid for Cell-free Tumor DNA in Children, Adolescents, and Young Adults With Brain Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CELECOXIB	4	2
ETOPOSIDE PHOSPHATE	4	2
TAZEMETOSTAT	4	2
EFLORNITHINE	4	1
FENOFIBRIC ACID	4	1
FLUDEOXYGLUCOSE F 18	4	1
PANOBINOSTAT	4	1
SONIDEGIB	4	1
TACROLIMUS ANHYDROUS	4	1
URSODIOL	4	1
ALISERTIB	3	1
BECOTATUG VEDOTIN	3	1
IDASANUTLIN	3	1
TIRAGOLUMAB	3	1
EFLORNITHINE, (S)-	2	1
PAXALISIB	2	1
CHEMBL5398431	0	2
CHEMBL344227	0	1
CHEMBL4446459	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items; also 4 diagnostic, 1 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
SMARCB1 Loss	Tazemetostat	Sensitivity/Response	CIViC B	EID11180