Bone osteosarcoma

Summary

Bone osteosarcoma (MONDO:0002629) is a disease (an umbrella term covering 5 Mondo subtypes) with 4 cohort genes and 1 clinical trial.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 4
• ClinVar variants: 221
• Phenotypes (HPO): 12
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.23	Europe	Validated
Lifetime Prevalence	1-9 / 100 000	3.17	Europe	Validated
Point prevalence	1-9 / 100 000		Europe	Validated
Annual incidence	1-9 / 1 000 000	0.4	United States	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0002797	Osteolysis	Very frequent (80-99%)
HP:0006489	Abnormality of the femoral metaphysis	Very frequent (80-99%)
HP:0000944	Abnormal metaphysis morphology	Frequent (30-79%)
HP:0001386	Joint swelling	Frequent (30-79%)
HP:0003155	Elevated circulating alkaline phosphatase concentration	Frequent (30-79%)
HP:0006491	Abnormality of the tibial metaphysis	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0025435	Increased circulating lactate dehydrogenase concentration	Frequent (30-79%)
HP:0045040	Abnormal lactate dehydrogenase activity	Frequent (30-79%)
HP:0001824	Weight loss	Very rare (<1-4%)
HP:0001945	Fever	Very rare (<1-4%)
HP:0002756	Pathologic fracture	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	bone osteosarcoma
Mondo ID	MONDO:0002629
OMIM	259500
Orphanet	668
DOID	DOID:3376
NCIT	C53707
SNOMED CT	307576001
UMLS	C0585442
MedGen	108437
GARD	0007284
MedDRA	10031291
Is cancer (heuristic)	no

Also known as: bone osteosarcoma · osteosarcoma of bone · osteosarcoma, somatic · osteosarcoma, somatic mutation

Data availability: 221 ClinVar variants.

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 › osteosarcoma › bone osteosarcoma

Related subtypes (5): localized osteosarcoma, extraosseous osteosarcoma, multifocal osteogenic sarcoma, pediatric osteosarcoma, low grade central osteosarcoma

Subtypes (5): peripheral osteosarcoma, conventional osteosarcoma, metachronous osteosarcoma of the bone, telangiectatic osteogenic sarcoma, osteosarcoma arising in bone Paget disease

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

221 retrieved; paginated sample, class counts are floors:

71 uncertain significance, 64 conflicting classifications of pathogenicity, 38 pathogenic/likely pathogenic, 23 pathogenic, 8 benign/likely benign, 6 likely benign, 6 likely pathogenic, 3 benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 conflicting classifications of pathogenicity; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066705	NM_007194.4(CHEK2):c.684-2A>G	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126914	NM_007194.4(CHEK2):c.444+1G>T	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128042	NM_007194.4(CHEK2):c.1100del (p.Thr367fs)	CHEK2	Pathogenic	criteria provided, multiple submitters, no conflicts
128053	NM_007194.4(CHEK2):c.1263del (p.Ser422fs)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128064	NM_007194.4(CHEK2):c.1555C>T (p.Arg519Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128071	NM_007194.4(CHEK2):c.349A>G (p.Arg117Gly)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128075	NM_007194.4(CHEK2):c.444+1G>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
133887	NM_007194.4(CHEK2):c.58C>T (p.Gln20Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140772	NM_007194.4(CHEK2):c.283C>T (p.Arg95Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141381	NM_007194.4(CHEK2):c.216T>G (p.Tyr72Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142352	NM_007194.4(CHEK2):c.319+2T>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142524	NM_007194.4(CHEK2):c.499G>A (p.Gly167Arg)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142956	NM_007194.4(CHEK2):c.592+3A>T	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182430	NM_007194.4(CHEK2):c.793-1G>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182450	NM_007194.4(CHEK2):c.1368dup (p.Glu457fs)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182452	NM_007194.4(CHEK2):c.409C>T (p.Arg137Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
185097	NM_007194.4(CHEK2):c.902del (p.Leu301fs)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2116199	NM_007194.4(CHEK2):c.107del (p.Gln36fs)	CHEK2	Pathogenic	criteria provided, multiple submitters, no conflicts
216003	NM_007194.4(CHEK2):c.593-1G>T	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216652	NM_007194.4(CHEK2):c.846+4_846+7del	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265565	NM_007194.4(CHEK2):c.1461+1G>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3893057	NM_007194.4(CHEK2):c.1241del (p.Gly414fs)	CHEK2	Pathogenic	criteria provided, single submitter
422638	NM_007194.4(CHEK2):c.444+2T>C	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
439092	NM_007194.4(CHEK2):c.417C>A (p.Tyr139Ter)	CHEK2	Pathogenic	criteria provided, multiple submitters, no conflicts
481726	NM_007194.4(CHEK2):c.319+1G>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
491586	NM_007194.4(CHEK2):c.100C>T (p.Gln34Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
491635	NM_007194.4(CHEK2):c.757A>T (p.Lys253Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
491642	NM_007194.4(CHEK2):c.793-2A>G	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5595	NM_007194.4(CHEK2):c.49G>T (p.Ala17Ser)	CHEK2	Pathogenic	no assertion criteria provided
663531	NM_007194.4(CHEK2):c.31C>T (p.Gln11Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 36 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
TSC2	Orphanet:210159	Adult hepatocellular carcinoma
TSC2	Orphanet:269001	Isolated focal cortical dysplasia type IIa
TSC2	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC2	Orphanet:538	Lymphangioleiomyomatosis
TSC2	Orphanet:805	Tuberous sclerosis complex
TSC2	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
CHEK2	Orphanet:1331	Familial prostate cancer
CHEK2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
CHEK2	Orphanet:440437	Familial colorectal cancer Type X
CHEK2	Orphanet:524	Li-Fraumeni syndrome
CHEK2	Orphanet:668	Osteosarcoma
RB1	Orphanet:1587	Monosomy 13q14 syndrome
RB1	Orphanet:357027	Hereditary retinoblastoma
RB1	Orphanet:357034	Non-hereditary retinoblastoma
RB1	Orphanet:668	Osteosarcoma
RB1	Orphanet:70573	Small cell lung cancer

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
TSC2	HGNC:12363	ENSG00000103197	P49815	Tuberin	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	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.
TSC2	Tuberin	Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule…
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.
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	6.9×	0.410
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

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
TSC2	Other/Unknown	no		Rap/Ran_GAP_dom, Tuberin, ARM-like
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
lower esophagus mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
choroid plexus epithelium	1
epithelium of nasopharynx	1
visceral pleura	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
TSC2	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
CHEK2	4,795
RB1	4,374
TSC2	4,135

Intra-cohort edges

A	B	Sources
CHEK2	TP53	intact, string_interaction
RB1	TP53	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
CHEK2	O96017	38
RB1	P06400	19
TSC2	P49815	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 70. Enrichment computed across 4 evidence-associated genes (4 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 4 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	2	380.7×	4e-04	TP53, CHEK2
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	2	335.9×	4e-04	TP53, RB1
Regulation of TP53 Activity through Methylation	2	271.9×	4e-04	TP53, CHEK2
Oncogene Induced Senescence	2	167.9×	9e-04	TP53, RB1
Regulation of TP53 Degradation	2	146.4×	1e-03	TP53, CHEK2
Defective translocation of RB1 mutants to the nucleus	1	2855.0×	0.003	RB1
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	2855.0×	0.003	TP53
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2	73.2×	0.003	TP53, CHEK2
TP53 Regulates Metabolic Genes	2	64.9×	0.003	TP53, TSC2
G2/M DNA damage checkpoint	2	60.1×	0.003	TP53, CHEK2
Regulation of TP53 Activity through Phosphorylation	2	58.9×	0.003	TP53, CHEK2
Regulation of TP53 Expression	1	1427.5×	0.004	TP53
Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes	1	713.8×	0.006	RB1
Transcriptional activation of cell cycle inhibitor p21	1	713.8×	0.006	TP53
Replication of the SARS-CoV-1 genome	1	713.8×	0.006	RB1
Replication of the SARS-CoV-2 genome	1	713.8×	0.006	RB1
Inhibition of TSC complex formation by AKT (PKB)	1	571.0×	0.007	TSC2
Activation of NOXA and translocation to mitochondria	1	475.8×	0.008	TP53
RUNX3 regulates CDKN1A transcription	1	407.9×	0.009	TP53
PI5P Regulates TP53 Acetylation	1	317.2×	0.011	TP53
Activation of PUMA and translocation to mitochondria	1	285.5×	0.012	TP53
TP53 Regulates Transcription of Caspase Activators and Caspases	1	237.9×	0.012	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	237.9×	0.012	TP53
Positive Regulation of CDH1 Gene Transcription	1	237.9×	0.012	RB1
Urea cycle	1	219.6×	0.012	TP53
Inhibition of replication initiation of damaged DNA by RB1/E2F1	1	203.9×	0.012	RB1
AKT phosphorylates targets in the cytosol	1	203.9×	0.012	TSC2
Regulation of TP53 Activity through Association with Co-factors	1	203.9×	0.012	TP53
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	190.3×	0.013	TP53
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	178.4×	0.013	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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to xenobiotic stimulus	3	180.6×	5e-05	TP53, CHEK2, RB1
negative regulation of glial cell proliferation	2	842.6×	1e-04	TP53, RB1
negative regulation of mitophagy	2	766.0×	1e-04	TP53, TSC2
thymocyte apoptotic process	2	702.2×	1e-04	TP53, CHEK2
replicative senescence	2	495.6×	2e-04	TP53, CHEK2
glial cell proliferation	2	443.5×	2e-04	TP53, RB1
regulation of cell cycle	3	55.9×	3e-04	TP53, TSC2, RB1
cellular response to gamma radiation	2	300.9×	4e-04	TP53, CHEK2
chromosome organization	2	290.6×	4e-04	TP53, RB1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	2	247.8×	5e-04	TP53, CHEK2
DNA damage response, signal transduction by p53 class mediator	2	179.3×	8e-04	TP53, CHEK2
Ras protein signal transduction	2	102.8×	0.002	TP53, RB1
double-strand break repair	2	101.5×	0.002	TP53, CHEK2
regulation of DNA-templated transcription	3	23.7×	0.002	TP53, CHEK2, RB1
neuron apoptotic process	2	92.6×	0.002	TP53, RB1
negative regulation of helicase activity	1	4213.0×	0.002	TP53
cellular response to actinomycin D	1	4213.0×	0.002	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	4213.0×	0.002	TP53
negative regulation of G1 to G0 transition	1	4213.0×	0.002	TP53
protein import into nucleus	2	72.0×	0.003	TP53, TSC2
negative regulation of cell growth	2	72.0×	0.003	TP53, RB1
positive regulation of mitochondrial membrane permeability	1	2106.5×	0.004	TP53
oligodendrocyte apoptotic process	1	2106.5×	0.004	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	2106.5×	0.004	TP53
negative regulation of pentose-phosphate shunt	1	2106.5×	0.004	TP53
intracellular protein localization	2	52.3×	0.004	TP53, TSC2
obsolete homolactic fermentation	1	1404.3×	0.004	TP53
sister chromatid biorientation	1	1404.3×	0.004	RB1
glial cell apoptotic process	1	1404.3×	0.004	RB1
signal transduction by p53 class mediator	1	1404.3×	0.004	TP53

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 4 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
TP53	NITROFURANTOIN
CHEK2	NERATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
CHEK2	30	4
RB1	1	2
TSC2	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): 1.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
CHEK2	690	Binding:687, Functional:2, ADMET:1
RB1	59	Binding:59
TSC2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK2	2.7.11.1	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
CHEK2	690

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
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)	2	TP53, CHEK2
B	Phased (≥1) drug, not yet approved	1	RB1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TSC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TSC2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03798587	Not specified	UNKNOWN	Inhibition of SENP1 for the Suppression of OS Growth and Metastasis