Sarcoma

Summary

Sarcoma (MONDO:0005089) is a cancer (an umbrella term covering 22 Mondo subtypes) caused by TP53 (GenCC Strong), with 22 cohort genes (21 CIViC-evidence somatic drivers; 16 ClinVar predisposition records) and 808 clinical trials. The dominant Reactome pathway is Stabilization of p53 (4 cohort genes). Molecularly, EWSR1::FLI1 Fusion OR EWSR1::WT1 Fusion OR EWSR1::ATF1 Fusion confers sensitivity to Trabectedin in Sarcoma (CIViC Level B); 17 further subtype–drug associations are mapped below. Top therapeutic interventions include dexrazoxane, ifosfamide, and 2-mercaptoethanesulfonic acid.

At a glance

• Classification: Cancer
• Causal gene: TP53 (GenCC Strong)
• Umbrella term: 22 Mondo subtypes
• Cohort genes: 22
• ClinVar variants: 16
• Clinical trials: 808
• Precision-medicine evidence (CIViC): 18 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sarcoma
Mondo ID	MONDO:0005089
EFO	EFO:0000691
MeSH	D012509
DOID	DOID:1115
NCIT	C9118
SNOMED CT	424413001
UMLS	C1261473
MedGen	224714
Is cancer (heuristic)	yes

Also known as: mesenchymal tumor, malignant · sarcoma · sarcoma of soft tissue and bone · sarcoma of the soft tissue and bone · sarcoma, malignant · tumour of soft tissue and skeleton

Data availability: 16 ClinVar variants · 6 GenCC gene-disease records · 8 cell lines.

Disease family

An umbrella term covering 22 Mondo subtypes.

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

Related subtypes (32): respiratory system cancer, immune system cancer, musculoskeletal system cancer, integumentary system cancer, peritoneum cancer, cardiovascular cancer, reproductive system cancer, malignant giant cell tumor, digestive system cancer, lipomatous cancer, thoracic cancer, malignant glomus tumor, malignant mesenchymoma, carcinoma, blastoma, head and neck cancer, malignant mixed neoplasm, nervous system cancer, retroperitoneal cancer, malignant germ cell tumor, malignant mesothelioma, malignant urinary system neoplasm, childhood malignant neoplasm, anaplastic cancer, malignant spindle cell neoplasm, high grade malignant neoplasm, malignant endocrine neoplasm, malignant soft tissue neoplasm, secondary malignant neoplasm, refractory malignant neoplasm, malignant adenoma, cancer of unknown primary site

Subtypes (22): rectum sarcoma, ectomesenchymoma, spindle cell sarcoma, colon sarcoma, sarcomatosis, dendritic cell sarcoma, orbit sarcoma, sarcoma G1, uterine corpus sarcoma, giant cell tumor of soft tissue, lymphangiosarcoma, endometrioid stromal sarcoma, myeloid sarcoma, small cell sarcoma, chondrosarcoma, osteosarcoma, reticulum cell sarcoma, Ewing sarcoma, sarcoma of cervix uteri, soft tissue sarcoma, mast cell sarcoma, bone sarcoma

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

16 retrieved; paginated sample, class counts are floors:

5 not provided, 3 likely benign, 2 pathogenic, 2 benign/likely benign, 2 pathogenic/likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
560005	NM_007194.4(CHEK2):c.341G>A (p.Trp114Ter)	CHEK2	Pathogenic	criteria provided, multiple submitters, no conflicts
13655	NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys)	PIK3CA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12356	NM_000546.6(TP53):c.743G>A (p.Arg248Gln)	TP53	Pathogenic	reviewed by expert panel
133282	NM_000546.6(TP53):c.448_459del (p.Thr150_Pro153del)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
90619	NM_000251.3(MSH2):c.128A>G (p.Tyr43Cys)	MSH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133284	NM_000546.6(TP53):c.460G>A (p.Gly154Ser)	TP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
132957	NM_000142.5(FGFR3):c.1887C>T (p.Asn629=)	FGFR3	Likely benign	criteria provided, single submitter
132959	NM_000142.5(FGFR3):c.1935C>T (p.Leu645=)	FGFR3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
132971	NM_033360.4(KRAS):c.219G>A (p.Arg73=)	KRAS	Likely benign	criteria provided, single submitter
132973	NM_000546.6(TP53):c.886C>T (p.His296Tyr)	TP53	Likely benign	reviewed by expert panel
132974	NM_000546.6(TP53):c.969G>A (p.Leu323=)	TP53	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
132958	NM_000142.5(FGFR3):c.1908C>G (p.Phe636Leu)	FGFR3	not provided	no classification provided
132968	NM_000142.5(FGFR3):c.2135G>A (p.Arg712His)	FGFR3	not provided	no classification provided
132970	NM_033360.4(KRAS):c.216G>A (p.Met72Ile)	KRAS	not provided	no classification provided
132966	NM_006218.2:c.1821+51A>T	PIK3CA	not provided	no classification provided
133283	NM_000546.6(TP53):c.450_459del (p.Pro151fs)	TP53	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 99 · Orphanet: 135 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
CDK4	LoF	MEL	CIViC #13
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
BCOR	LoF	ACC,AML,CHOL,CLLSLL,COADREAD,GBM,LGGNOS,LUAD,MBL,PAAD,PAST,PGNG,PLMESO,SIC,STAD,THYM,UCEC,UCS	CIViC #12555
ANTXR1	LoF	LUNG,MEL,STAD,UTUC	CIViC #524
PARP1			CIViC #199
ERCC2	Act	BLCA	CIViC #1736
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
HIF1A	Act	WDTC	CIViC #2596
IGF1R			CIViC #2899
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66
JAK1	LoF	ALL,BRCA,MLYM,OVT,PRAD,PROSTATE,STOMACH,UCEC	CIViC #3090
ASS1			CIViC #450
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69
RAD23B			CIViC #4760
CHEK2	Act	BRCA	CIViC #8950
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
MSH2			CIViC #3628
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TP53	Strong	Autosomal dominant	sarcoma	12
ANTXR1	Moderate	Autosomal dominant	sarcoma	16
APC	Moderate	Autosomal dominant	sarcoma	15
ATM	Moderate	Autosomal dominant	sarcoma	14
ATR	Moderate	Autosomal dominant	sarcoma	10
BRCA2	Moderate	Autosomal dominant	sarcoma	13
ERCC2	Moderate	Autosomal recessive	sarcoma	19

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
CDK4	Orphanet:618	Familial melanoma
CDK4	Orphanet:99970	Dedifferentiated liposarcoma
CDK4	Orphanet:99971	Well-differentiated liposarcoma
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
BCOR	Orphanet:2712	Oculofaciocardiodental syndrome
BCOR	Orphanet:457246	Clear cell sarcoma of kidney
BCOR	Orphanet:520	Acute promyelocytic leukemia
BCOR	Orphanet:568	Microphthalmia, Lenz type
ANTXR1	Orphanet:2067	GAPO syndrome
ERCC2	Orphanet:1466	COFS syndrome
ERCC2	Orphanet:220295	Xeroderma pigmentosum-Cockayne syndrome complex

Cohort genes → proteins

22 cohort genes, 22 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	10
multi_evidence	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gencc,clinvar,civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gencc
CDK4	HGNC:1773	ENSG00000135446	P11802	Cyclin-dependent kinase 4	civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	civic_evidence
ANTXR1	HGNC:21014	ENSG00000169604	Q9H6X2	Anthrax toxin receptor 1	gencc
PARP1	HGNC:270	ENSG00000143799	P09874	Poly [ADP-ribose] polymerase 1	civic_evidence
ERCC2	HGNC:3434	ENSG00000104884	P18074	General transcription and DNA repair factor IIH helicase subunit XPD	gencc
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
HIF1A	HGNC:4910	ENSG00000100644	Q16665	Hypoxia-inducible factor 1-alpha	civic_evidence
IGF1R	HGNC:5465	ENSG00000140443	P08069	Insulin-like growth factor 1 receptor	civic_evidence
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	gencc
JAK1	HGNC:6190	ENSG00000162434	P23458	Tyrosine-protein kinase JAK1	civic_evidence
ASS1	HGNC:758	ENSG00000130707	P00966	Argininosuccinate synthase	civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	gencc
ATR	HGNC:882	ENSG00000175054	Q13535	Serine/threonine-protein kinase ATR	gencc
RAD23B	HGNC:9813	ENSG00000119318	P54727	Lysine-specific demethylase RAD23B	civic_evidence
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
CDK4	Cyclin-dependent kinase 4	Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
BCOR	BCL-6 corepressor	Transcriptional corepressor.
ANTXR1	Anthrax toxin receptor 1	Plays a role in cell attachment and migration.
PARP1	Poly [ADP-ribose] polymerase 1	Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
ERCC2	General transcription and DNA repair factor IIH helicase subunit XPD	ATP-dependent 5’-3’ DNA helicase.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
HIF1A	Hypoxia-inducible factor 1-alpha	Functions as a master transcriptional regulator of the adaptive response to hypoxia.
IGF1R	Insulin-like growth factor 1 receptor	Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1).
APC	Adenomatous polyposis coli protein	Tumor suppressor.
JAK1	Tyrosine-protein kinase JAK1	Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway.
ASS1	Argininosuccinate synthase	One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals.
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
ATR	Serine/threonine-protein kinase ATR	Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor.
RAD23B	Lysine-specific demethylase RAD23B	Multifunctional protein that participates in histone H4K20 demethylation, DNA repair, ubiquitin-dependent protein degradation and transcriptional regulation.
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

Protein-family classification

Druggable: 12 · Difficult: 5 · Unknown: 5 · Druggable fraction: 0.55

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	9	11.3×	2e-07
Enzyme (other)	3	1.6×	0.610
Scaffold/PPI	2	1.6×	0.610
Transcription factor	3	1.1×	0.635
Other/Unknown	5	0.4×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
CDK4	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD
ANTXR1	Other/Unknown	no		VWF_A, Anthrax_toxin_rcpt_C, Anthrax_toxin_rcpt_extracel
PARP1	Transcription factor	no	2.4.2.30	BRCT_dom, Znf_PARP, Poly(ADP-ribose)pol_reg_dom
ERCC2	Enzyme (other)	yes	3.6.4.12	RAD3/XPD, DNA/RNA_helicase_DEAH_CS, Helicase-like_DEXD_c2
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
HIF1A	Transcription factor	no		PAS, HIF-1_alpha, PAC
IGF1R	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
JAK1	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
ASS1	Enzyme (other)	yes	6.3.4.5	Arginosuc_synth, Rossmann-like_a/b/a_fold, Arginosuc_synth_CS
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
ATR	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
RAD23B	Other/Unknown	no		Ubiquitin-like_dom, Rad23, STI1_HS-bd
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom

Expression context

Cohort genes with no expression data: 0.

22 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)	22
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	5
ganglionic eminence	4
calcaneal tendon	4
stromal cell of endometrium	3
corpus epididymis	3
adrenal tissue	3
male germ line stem cell (sensu Vertebrata) in testis	2
secondary oocyte	2
buccal mucosa cell	2
palpebral conjunctiva	2
primordial germ cell in gonad	2
skin of hip	2
tendon of biceps brachii	1
embryo	1
cervix squamous epithelium	1
parotid gland	1
pituitary gland	1
cortical plate	1
decidua	1
left adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
CDK4	138	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
BCOR	265	ubiquitous	marker	buccal mucosa cell, ganglionic eminence, cortical plate
ANTXR1	270	ubiquitous	marker	stromal cell of endometrium, decidua, palpebral conjunctiva
PARP1	292	ubiquitous	marker	ventricular zone, ganglionic eminence, primordial germ cell in gonad
ERCC2	184	ubiquitous	marker	stromal cell of endometrium, right adrenal gland, left adrenal gland
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
HIF1A	295	ubiquitous	marker	pancreatic ductal cell, epithelial cell of pancreas, corpus epididymis
IGF1R	285	ubiquitous	marker	caput epididymis, corpus epididymis, adrenal tissue
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus
JAK1	295	ubiquitous	marker	type B pancreatic cell, skin of hip, calcaneal tendon
ASS1	292	ubiquitous	marker	right lobe of liver, palpebral conjunctiva, liver
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
ATR	289	ubiquitous	marker	Brodmann (1909) area 23, epithelium of nasopharynx, adrenal tissue
RAD23B	295	ubiquitous	marker	corpus epididymis, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon

Protein interactions among cohort

Intra-cohort edges: 21.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
HIF1A	9,734
CDKN2A	9,311
CDK4	8,412
PARP1	8,370
ATM	7,383
IGF1R	6,823
FGFR1	5,693
RAD23B	5,287

Intra-cohort edges

A	B	Sources
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	HIF1A	biogrid_interaction
ATM	MSH2	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
ATR	CHEK2	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	PARP1	string_interaction
BRCA2	TP53	string_interaction
CDK4	CDKN2A	biogrid_interaction, intact, string_interaction
CDKN2A	HIF1A	string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	TP53	string_interaction
CHEK2	TP53	intact, string_interaction
ERCC2	RAD23B	string_interaction
FGFR3	PIK3CA	string_interaction
HIF1A	TP53	string_interaction
KRAS	PIK3CA	string_interaction
KRAS	TP53	string_interaction
PARP1	TP53	intact

Structural data

PDB: 22 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
PIK3CA	P42336	135
PARP1	P09874	106
FGFR1	P11362	83
ERCC2	P18074	51
JAK1	P23458	51
IGF1R	P08069	46
CHEK2	O96017	38
APC	P25054	31
MSH2	P43246	30
HIF1A	Q16665	25
CDK4	P11802	15
FGFR3	P22607	15
BRCA2	P51587	14
ATM	Q13315	14
RAD23B	P54727	12
ATR	Q13535	10
CDKN2A	P42771	5
BCOR	Q6W2J9	5
ANTXR1	Q9H6X2	5
ASS1	P00966	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 418. Enrichment computed across 22 evidence-associated genes (21 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 21 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Stabilization of p53	4	145.0×	5e-06	TP53, CHEK2, CDKN2A, ATM
Diseases of DNA repair	4	108.8×	8e-06	BRCA2, MSH2, ATM, ATR
TP53 Regulates Transcription of DNA Repair Genes	5	43.2×	1e-05	TP53, ERCC2, MSH2, ATM, ATR
Regulation of TP53 Degradation	4	55.8×	6e-05	TP53, CHEK2, CDKN2A, ATM
Meiosis	4	54.4×	6e-05	BRCA2, CDK4, ATM, ATR
Diseases of DNA Double-Strand Break Repair	3	116.5×	1e-04	BRCA2, ATM, ATR
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	3	116.5×	1e-04	BRCA2, ATM, ATR
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	2	543.8×	1e-04	CDK4, CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	2	543.8×	1e-04	CDK4, CDKN2A
Reproduction	4	36.2×	2e-04	BRCA2, CDK4, ATM, ATR
Diseases of Cellular Senescence	2	362.5×	2e-04	CDK4, CDKN2A
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	2	362.5×	2e-04	CDK4, CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	362.5×	2e-04	CDK4, CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	2	362.5×	2e-04	CDK4, CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	362.5×	2e-04	CDK4, CDKN2A
Diseases of cellular response to stress	2	362.5×	2e-04	CDK4, CDKN2A
Regulation of TP53 Activity through Methylation	3	77.7×	2e-04	TP53, CHEK2, ATM
Signaling by FGFR3 in disease	3	70.9×	2e-04	FGFR3, KRAS, PIK3CA
RAF/MAP kinase cascade	5	14.5×	4e-04	FGFR1, FGFR3, JAK1, KRAS, PIK3CA
Homologous DNA Pairing and Strand Exchange	3	54.4×	4e-04	BRCA2, ATM, ATR
G2/M DNA damage checkpoint	4	22.9×	5e-04	TP53, CHEK2, ATM, ATR
Regulation of TP53 Activity through Phosphorylation	4	22.4×	5e-04	TP53, CHEK2, ATM, ATR
Oncogene Induced Senescence	3	48.0×	6e-04	TP53, CDK4, CDKN2A
Homology Directed Repair	3	44.1×	6e-04	BRCA2, ATM, ATR
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3	44.1×	6e-04	BRCA2, ATM, ATR
Impaired BRCA2 binding to RAD51	3	44.1×	6e-04	BRCA2, ATM, ATR
Signaling by FGFR1 in disease	3	41.8×	7e-04	FGFR1, KRAS, PIK3CA
DNA Repair	4	18.8×	8e-04	BRCA2, MSH2, ATM, ATR
PI3K Cascade	3	38.8×	8e-04	FGFR1, FGFR3, PIK3CA
Presynaptic phase of homologous DNA pairing and strand exchange	3	38.8×	8e-04	BRCA2, ATM, ATR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
replicative senescence	5	225.3×	4e-09	TP53, CHEK2, CDKN2A, ATM, ATR
double-strand break repair	7	64.6×	4e-09	TP53, BRCA2, CHEK2, PARP1, MSH2, ATM, ATR
cellular response to gamma radiation	4	109.4×	9e-06	TP53, CHEK2, ATM, ATR
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	4	90.1×	2e-05	TP53, BRCA2, CHEK2, MSH2
determination of adult lifespan	4	78.6×	2e-05	TP53, ERCC2, MSH2, ATM
nucleotide-excision repair	4	69.6×	3e-05	TP53, BRCA2, ERCC2, RAD23B
DNA damage response, signal transduction by p53 class mediator	4	65.2×	3e-05	TP53, BRCA2, CHEK2, ATM
cellular senescence	4	53.8×	6e-05	TP53, BRCA2, CDKN2A, ATM
establishment of RNA localization to telomere	2	766.0×	8e-05	ATM, ATR
establishment of protein-containing complex localization to telomere	2	766.0×	8e-05	ATM, ATR
positive regulation of telomerase catalytic core complex assembly	2	766.0×	8e-05	ATM, ATR
positive regulation of DNA damage response, signal transduction by p53 class mediator	3	135.2×	8e-05	CDKN2A, ATM, ATR
response to X-ray	3	121.0×	9e-05	TP53, BRCA2, MSH2
DNA damage response	6	14.6×	1e-04	TP53, CHEK2, PARP1, APC, ATM, ATR
neuron apoptotic process	4	33.7×	2e-04	TP53, HIF1A, KRAS, ATM
response to gamma radiation	3	79.2×	3e-04	TP53, BRCA2, PARP1
insulin-like growth factor receptor signaling pathway	3	67.6×	4e-04	ERCC2, IGF1R, PIK3CA
embryonic organ development	3	65.7×	4e-04	TP53, ERCC2, RAD23B
protein autophosphorylation	4	26.4×	5e-04	CHEK2, FGFR1, IGF1R, ATM
positive regulation of phospholipase activity	2	306.4×	5e-04	FGFR1, FGFR3
negative regulation of mammary gland epithelial cell proliferation	2	306.4×	5e-04	BRCA2, CDKN2A
DNA damage checkpoint signaling	3	53.4×	6e-04	CHEK2, ATM, ATR
positive regulation of protein localization to nucleus	3	53.4×	6e-04	CDKN2A, PARP1, JAK1
mitochondrial DNA repair	2	218.9×	9e-04	TP53, PARP1
negative regulation of cyclin-dependent protein serine/threonine kinase activity	2	191.5×	0.001	CDKN2A, APC
chondrocyte differentiation	3	41.0×	0.001	FGFR1, FGFR3, HIF1A
cellular response to UV	3	40.3×	0.001	TP53, PARP1, ATR
bone mineralization	3	37.1×	0.002	ERCC2, FGFR3, HIF1A
telomere maintenance	3	36.5×	0.002	PARP1, ATM, ATR
thymocyte apoptotic process	2	127.7×	0.002	TP53, CHEK2

Therapeutics

Drugs indicated for this disease

3 approved, 30 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Olaratumab	Approved (phase 4)
Tasonermin	Approved (phase 4)
Trabectedin	Approved (phase 4)
Busulfan	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Catequentinib	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Dacarbazine	Phase 3 (in late-stage trials)
Dactinomycin	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Eribulin	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Imatinib	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Ombrabulin	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Palbociclib	Phase 3 (in late-stage trials)
Palifosfamide	Phase 3 (in late-stage trials)
Pazopanib	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Recombinant Human Thrombopoietin	Phase 3 (in late-stage trials)
Ridaforolimus	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)
Tazemetostat	Phase 3 (in late-stage trials)
Trofosfamide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): 6-O-BENZYLGUANINE, Alectinib, Alvocidib, Amifostine, Atezolizumab, Bempegaldesleukin, Bevacizumab, Bortezomib, Camrelizumab, Carmustine, Celecoxib, Cetuximab, Cyclosporine, Cytarabine, Dalpiciclib, Dostarlimab, Durvalumab, Envafolimab, Epacadostat, Everolimus, Fludarabine Phosphate, Fluzoparib, Gefitinib, Glycerin, Hydroxychloroquine, Interferon Alfa, Irinotecan, Lenvatinib, Lomustine, Lurbinectedin, Milademetan, Mitomycin, Nicotine, Nintedanib, Olaparib, Ondansetron, Pembrolizumab, Pemetrexed, Pracinostat, Regorafenib, Retifanlimab, Ritonavir, Rivoceranib, Selumetinib, Semaxanib, Sintilimab, Sirolimus, Sorafenib, Sunitinib, Surufatinib, Tacrolimus Anhydrous, Talimogene Laherparepvec, Tasisulam, Temozolomide, Temsirolimus, Teprotumumab, Thalidomide, Thiotepa, Topotecan, Toripalimab, Trastuzumab, Tremelimumab, Troglitazone, Tucidinostat, Vatalanib, Vinorelbine, Vitespen, Vorinostat.

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 14 · Phased (≥1): 14 · Undrugged: 8

Druggability breadth: 20 of 22 evidence-associated genes (91%) 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
CDK4	PALBOCICLIB
PARP1	NIRAPARIB
ERCC2	SUNITINIB
FGFR1	PONATINIB
HIF1A	EMETINE
IGF1R	FEDRATINIB
JAK1	FEDRATINIB
ATM	AMIODARONE HYDROCHLORIDE
CHEK2	NERATINIB
FGFR3	PONATINIB
KRAS	VEMURAFENIB
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HIF1A	255	4
TP53	196	4
FGFR1	93	4
JAK1	68	4
PIK3CA	67	4
FGFR3	64	4
CDK4	56	4
ATM	35	4
CHEK2	30	4
IGF1R	27	4

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	HIF1A, TP53
CLOTRIMAZOLE	4	HIF1A, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	HIF1A, TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	HIF1A, TP53
SULCONAZOLE NITRATE	4	HIF1A, TP53
PYRITHIONE ZINC	4	HIF1A, 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	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	HIF1A, TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
JAK1	1,502	Binding:1428, Functional:49, ADMET:24, Toxicity:1
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
CDK4	1,142	Binding:1086, Functional:53, ADMET:2, Toxicity:1
IGF1R	1,091	Binding:1037, Functional:53, ADMET:1
FGFR3	975	Binding:948, Functional:18, ADMET:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
PARP1	825	Binding:814, Functional:8, ADMET:3
CHEK2	690	Binding:687, Functional:2, ADMET:1
HIF1A	427	Binding:411, Functional:16
ATM	240	Binding:233, Functional:5, ADMET:2
ATR	231	Binding:226, Functional:5
APC	24	Binding:24
MSH2	9	Binding:9
ERCC2	3	Binding:3
CDKN2A	2	Binding:2
BCOR	2	Binding:2
ASS1	1	Binding:1
RAD23B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CDK4	2.7.11.22	cyclin-dependent kinase
PARP1	2.4.2.30	NAD+ ADP-ribosyltransferase
ERCC2	3.6.4.12	DNA helicase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
IGF1R	2.7.10.1	receptor protein-tyrosine kinase
JAK1	2.7.10.2	non-specific protein-tyrosine kinase
ASS1	6.3.4.5	argininosuccinate synthase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
ATR	2.7.11.1	non-specific serine/threonine protein kinase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869
CDK4	1,142
PARP1	825
FGFR1	1,465
HIF1A	427
IGF1R	1,091
JAK1	1,502
ATM	240
ATR	231
CHEK2	690
FGFR3	975
KRAS	861
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 22; 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	HIF1A, TP53
CLOTRIMAZOLE	4	HIF1A, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	HIF1A, TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	HIF1A, TP53
SULCONAZOLE NITRATE	4	HIF1A, TP53
PYRITHIONE ZINC	4	HIF1A, 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	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	HIF1A, 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)	13	TP53, CDK4, PARP1, ERCC2, FGFR1, HIF1A, IGF1R, JAK1, ATM, CHEK2 (+3 more)
B	Phased (≥1) drug, not yet approved	1	ATR
C	Druggable family + PDB, no drug	1	ASS1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	7	BRCA2, CDKN2A, BCOR, ANTXR1, APC, RAD23B, MSH2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDKN2A	2	CDK4
BRCA2	0	—
BCOR	2	—
ANTXR1	0	—
APC	24	—
ASS1	1	—
RAD23B	1	—
MSH2	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 808.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	255
Not specified	255
PHASE1	161
PHASE1/PHASE2	69
PHASE3	42
EARLY_PHASE1	20
PHASE4	3
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03144206	PHASE4	ACTIVE_NOT_RECRUITING	Hyperbaric Oxygen Therapy for Soft Tissue Sarcoma Pilot Study
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT04033081	PHASE4	ACTIVE_NOT_RECRUITING	Registry of Sarcoma Patients Treated With Permanently Implantable LDR CivaSheet®
NCT00470223	PHASE3	ACTIVE_NOT_RECRUITING	Combined Chemotherapy With or Without Zoledronic Acid for Patients With Osteosarcoma
NCT01223248	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Study Comparing Two Dosing Schedules for Hypofractionated Image-Guided Radiation Therapy
NCT02413736	PHASE3	ACTIVE_NOT_RECRUITING	Three Versus Five Years of Adjuvant Imatinib as Treatment of Patients With Operable GIST
NCT00001300	PHASE3	COMPLETED	A Randomized Study of the Effect of Adjuvant Chemotherapy With Doxorubicin and Ifosfamide With Mesna in the Treatment of High-Grade Adult Extremity Soft Tissue Sarcoma
NCT00002459	PHASE3	COMPLETED	Radiation Therapy or No Further Treatment Following Surgery in Treating Patients With Cancer of the Uterus
NCT00002516	PHASE3	UNKNOWN	Combination Chemotherapy Plus Surgery and Radiation Therapy in Treating Patients With Ewing’s Sarcoma
NCT00002539	PHASE3	COMPLETED	Combination Chemotherapy and Surgery With or Without G-CSF in Treating Patients With Osteosarcoma
NCT00002546	PHASE3	COMPLETED	Radiation Therapy Compared With Combination Chemotherapy in Treating Patients With Cancer of the Uterus
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002898	PHASE3	COMPLETED	Surgery Followed by Chemotherapy in Treating Young Patients With Soft Tissue Sarcoma
NCT00002985	PHASE3	COMPLETED	Doxorubicin in Treating Patients With AIDS-Related Kaposi’s Sarcoma
NCT00002995	PHASE3	COMPLETED	Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
NCT00003052	PHASE3	COMPLETED	Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma
NCT00003128	PHASE3	COMPLETED	Ifosfamide With or Without Paclitaxel in Treating Patients With Advanced, Refractory, or Recurrent Cancer of the Uterus
NCT00003212	PHASE3	COMPLETED	Ifosfamide or Doxorubicin in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma
NCT00003937	PHASE3	COMPLETED	Combination Chemotherapy Plus Dexrazoxane in Treating Patients With Newly Diagnosed Nonmetastatic Osteosarcoma
NCT00006734	PHASE3	COMPLETED	Comparison of Combination Chemotherapy Regimens in Treating Patients With Ewing’s Sarcoma or Neuroectodermal Tumor
NCT00020566	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation, Radiation Therapy, and/or Surgery in Treating Patients With Ewing’s Sarcoma
NCT00033605	PHASE3	COMPLETED	Octreotide in Preventing Diarrhea in Patients Who Are Undergoing Radiation Therapy to the Pelvis
NCT00038311	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00061984	PHASE3	COMPLETED	Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma
NCT00091351	PHASE3	COMPLETED	Surgery With or Without Radiation Therapy in Treating Patients With Primary Soft Tissue Sarcoma of the Retroperitoneum or Pelvis
NCT00116935	PHASE3	COMPLETED	Study Comparing 12 Months Versus 36 Months of Imatinib in the Treatment of Gastrointestinal Stromal Tumor (GIST)
NCT00131898	PHASE3	COMPLETED	A Prospective Randomized Trial of Pre-Operative IMRT+Surgery Versus Surgery Alone For Primary Retroperitoneal Sarcoma
NCT00283582	PHASE3	COMPLETED	Trial of Primary Prophylaxis With rhTPO Administered to Patients With High Risk Sarcoma Receiving Intensive Chemotherapy
NCT00334854	PHASE3	UNKNOWN	Ifosfamide and Doxorubicin, Radiation Therapy, and/or Surgery in Treating Young Patients With Localized Soft Tissue Sarcoma
NCT00334867	PHASE3	WITHDRAWN	Combination Chemotherapy With or Without Topotecan in Treating Patients With Newly Diagnosed Localized Ewing’s Sarcoma
NCT00354744	PHASE3	COMPLETED	High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma
NCT00354835	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
NCT00367861	PHASE3	COMPLETED	Prospective Multicentric Randomized Study of Glivec® in Advanced GIST Expressing C-kit: Interruption After 5 Years vs Maintenance
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00379457	PHASE3	UNKNOWN	Combination Chemotherapy in Treating Young Patients With Nonmetastatic Rhabdomyosarcoma
NCT00423618	PHASE3	COMPLETED	Randomised Trial of Volume of Post-operative Radiotherapy Given to Adult Patients With eXtremity Soft Tissue Sarcoma
NCT00699517	PHASE3	COMPLETED	A Study of AVE8062 in Advanced-stage Soft Tissue Sarcoma After Failure of Anthracycline and Ifosfamide Chemotherapies
NCT00716976	PHASE3	COMPLETED	Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
NCT00782145	PHASE3	COMPLETED	A Web-Based Stem Cell Transplant Support System or Standard Care in Young Patients Undergoing Stem Cell Transplant and Their Families

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEXRAZOXANE	4	22
IFOSFAMIDE	4	20
2-MERCAPTOETHANESULFONIC ACID	4	14
DACTINOMYCIN	4	14
TRABECTEDIN	4	13
DOXORUBICIN	4	12
IMATINIB	4	12
TEMOZOLOMIDE	4	10
FLUDARABINE PHOSPHATE	4	7
ETOPOSIDE	4	6
FILGRASTIM	4	6
TOPOTECAN HYDROCHLORIDE	4	6
AMIFOSTINE	4	5
DACARBAZINE	4	5
PEGFILGRASTIM	4	5
VINCRISTINE SULFATE	4	5
CISPLATIN	4	3
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
EPIRUBICIN HYDROCHLORIDE	4	3
MITOMYCIN	4	3
SARGRAMOSTIM	4	3
THIOTEPA	4	3
TRIMETREXATE GLUCURONATE	4	3
VINORELBINE TARTRATE	4	3
GLUTAMINE	4	2
IRINOTECAN HYDROCHLORIDE	4	2
SODIUM THIOSULFATE	4	2
ALDESLEUKIN	4	1
ARSENIC TRIOXIDE	4	1
BUSULFAN	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 18 predictive associations from 20 curated evidence items; also 3 prognostic, 3 diagnostic, 2 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
EWSR1::FLI1 Fusion OR EWSR1::WT1 Fusion OR EWSR1::ATF1 Fusion	Trabectedin	Sensitivity/Response	CIViC B	EID12544
IGF1R NUCLEAR EXPRESSION	IGF1R Monoclonal Antibody	Sensitivity/Response	CIViC B	EID924
NTRK1 Fusion	Larotrectinib	Sensitivity/Response	CIViC B	EID6569
TP53 Deleterious Mutation	Pazopanib	Sensitivity/Response	CIViC B	EID1170
LMNA::NTRK1 Fusion	Larotrectinib	Sensitivity/Response	CIViC C	EID2955 +1
PDE4DIP::NTRK1 Fusion	Larotrectinib	Sensitivity/Response	CIViC C	EID6102 +1
ERC1::ALK Fusion	Crizotinib	Sensitivity/Response	CIViC C	EID11032
JAK1 OVEREXPRESSION	Ruxolitinib	Sensitivity/Response	CIViC C	EID7852
STRN::NTRK2 Fusion	Larotrectinib	Sensitivity/Response	CIViC C	EID6098
TP53 R175H OR TP53 H193R	Pazopanib + Vorinostat	Sensitivity/Response	CIViC C	EID7540
TPM3::NTRK1 Fusion	Larotrectinib	Sensitivity/Response	CIViC C	EID6101
ASS1 Loss	Chloroquine + Pegargiminase	Sensitivity/Response	CIViC D	EID5988
ATM Mutation OR TP53 Mutation OR PIK3R1 Mutation OR PIK3CB Mutation OR NTRK1 Mutation OR CSF2RB Mutation	Doxorubicin	Sensitivity/Response	CIViC D	EID12721
CDK4 EXPRESSION	Palbociclib	Sensitivity/Response	CIViC D	EID4872
FGFR1 Expression	Fexagratinib + FGF/VEGF Receptor Tyrosine Kinase Inhibitor + PD173074 + Infigratinib	Sensitivity/Response	CIViC D	EID2915
PARP1 OVEREXPRESSION	Trabectedin + Olaparib	Sensitivity/Response	CIViC D	EID7868
RAD23B EXPRESSION	Vorinostat	Sensitivity/Response	CIViC D	EID1597
CDKN2A p16 Expression	Palbociclib	Resistance	CIViC D	EID4873