Cancer or benign tumor

Summary

Cancer or benign tumor (MONDO:0045024) is a cancer (an umbrella term covering 5 Mondo subtypes) with 10 cohort genes (10 CIViC-evidence somatic drivers; 13 ClinVar predisposition records) and 1,248 clinical trials. The dominant Reactome pathway is HDR through Homologous Recombination (HRR) (4 cohort genes). Top therapeutic interventions include dostarlimab, epoetin alfa, and dacomitinib anhydrous.

At a glance

• Classification: Cancer
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 10
• ClinVar variants: 13
• Clinical trials: 1,248

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cancer or benign tumor
Mondo ID	MONDO:0045024
Is cancer (heuristic)	yes

Also known as: cell proliferation disorder · neoplasm

Data availability: 13 ClinVar variants · 43 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor

Related subtypes (4): nutritional disorder, idiopathic disease, disease of genetic or genomic mechanism, disease of primarily extrinsic mechanism

Subtypes (5): hyperplasia, polyp, precancerous condition, neoplastic disease or syndrome, cancer-related condition

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

13 retrieved; paginated sample, class counts are floors:

8 conflicting classifications of pathogenicity, 2 uncertain significance, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
9347	NM_000059.4(BRCA2):c.9196C>T (p.Gln3066Ter)	BRCA2	Pathogenic	reviewed by expert panel
128053	NM_007194.4(CHEK2):c.1263del (p.Ser422fs)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
470051	NM_000038.6(APC):c.6512G>A (p.Gly2171Glu)	APC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127413	NM_000051.4(ATM):c.5882A>G (p.Tyr1961Cys)	ATM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
142503	NM_000051.4(ATM):c.2804C>T (p.Thr935Met)	ATM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
51210	NM_000059.4(BRCA2):c.1826A>G (p.Gln609Arg)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
52546	NM_000059.4(BRCA2):c.8324T>C (p.Met2775Thr)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
242140	NM_177438.3(DICER1):c.5527+7T>A	DICER1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127770	NM_000535.7(PMS2):c.2012C>T (p.Thr671Met)	PMS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141519	NM_002878.4(RAD51D):c.796C>T (p.Arg266Cys)	RAD51D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
405805	NM_006231.4(POLE):c.6049C>T (p.Arg2017Cys)	POLE	Uncertain significance	criteria provided, multiple submitters, no conflicts
4075267	NM_004168.4(SDHA):c.887A>G (p.His296Arg)	SDHA	Uncertain significance	criteria provided, multiple submitters, no conflicts
215673	NM_000251.3(MSH2):c.2210+7G>T	MSH2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 53 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SDHA	Act	CHRCC,HCC,LGGNOS	CIViC #5176
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
CHEK2	Act	BRCA	CIViC #8950
DICER1	LoF	COADREAD,CSCC,MEL,UCEC	CIViC #9533
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
MSH2			CIViC #3628
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
PMS2	ambiguous	HCC	CIViC #4371
POLE	Act	ACC,BLCA	CIViC #4386
RAD51D			CIViC #4765

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDHA	Orphanet:139411	Carney triad
SDHA	Orphanet:154	Familial isolated dilated cardiomyopathy
SDHA	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHA	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHA	Orphanet:44890	Gastrointestinal stromal tumor
SDHA	Orphanet:97286	Carney-Stratakis syndrome
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
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
DICER1	Orphanet:276399	Familial multinodular goiter
DICER1	Orphanet:284343	DICER1 tumor-predisposition syndrome
DICER1	Orphanet:404476	Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome
DICER1	Orphanet:99757	Embryonal rhabdomyosarcoma
DICER1	Orphanet:99914	Gynandroblastoma
DICER1	Orphanet:99915	Malignant granulosa cell tumor of the ovary
DICER1	Orphanet:99916	Malignant Sertoli-Leydig cell tumor of the ovary
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach
APC	Orphanet:3258	Cenani-Lenz syndrome
APC	Orphanet:873	Desmoid tumor
MSH2	Orphanet:144	Lynch syndrome
MSH2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia
PMS2	Orphanet:144	Lynch syndrome
PMS2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
POLE	Orphanet:352712	Facial dysmorphism-immunodeficiency-livedo-short stature syndrome
POLE	Orphanet:440437	Familial colorectal cancer Type X
POLE	Orphanet:447877	Polymerase proofreading-related polyposis

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDHA	HGNC:10680	ENSG00000073578	P31040	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
DICER1	HGNC:17098	ENSG00000100697	Q9UPY3	Endoribonuclease Dicer	clinvar
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	clinvar
POLE	HGNC:9177	ENSG00000177084	Q07864	DNA polymerase epsilon catalytic subunit A	clinvar
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDHA	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
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.
DICER1	Endoribonuclease Dicer	Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing.
APC	Adenomatous polyposis coli protein	Tumor suppressor.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
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.
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
POLE	DNA polymerase epsilon catalytic subunit A	Catalytic component of the DNA polymerase epsilon complex.
RAD51D	DNA repair protein RAD51 homolog 4	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.3

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	2	5.5×	0.193
Enzyme (other)	1	1.2×	0.725
Other/Unknown	6	1.1×	0.725
Transcription factor	1	0.8×	0.725

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDHA	Other/Unknown	no		FRD_SDH_FAD_BS, FAD-dep_OxRdtase_2_FAD-bd, Succ_DH_flav_su_fwd
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
DICER1	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, Helicase_C-like, PAZ_dom
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
POLE	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B, RNaseH-like_sf
RAD51D	Other/Unknown	no		AAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like

Expression context

Cohort genes with no expression data: 0.

9 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
secondary oocyte	2
ventricular zone	2
oocyte	2
apex of heart	1
heart left ventricle	1
mucosa of transverse colon	1
lower esophagus mucosa	1
primordial germ cell in gonad	1
caput epididymis	1
cauda epididymis	1
tongue squamous epithelium	1
medial globus pallidus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1
prefrontal cortex	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDHA	143	ubiquitous	marker	apex of heart, heart left ventricle, mucosa of transverse colon
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
DICER1	295	ubiquitous	marker	cauda epididymis, caput epididymis, tongue squamous epithelium
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
POLE	221	ubiquitous	marker	right hemisphere of cerebellum, right testis, cerebellar hemisphere
RAD51D	187	ubiquitous	yes	sperm, male germ cell, oocyte

Protein interactions among cohort

Intra-cohort edges: 13.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DICER1	8,268
ATM	7,383
SDHA	6,141
BRCA2	4,839
CHEK2	4,795
MSH2	4,537
POLE	3,267
RAD51D	3,089
APC	2,903
PMS2	2,658

Intra-cohort edges

A	B	Sources
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	MSH2	string_interaction
ATM	RAD51D	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	PMS2	string_interaction
BRCA2	RAD51D	string_interaction
CHEK2	RAD51D	string_interaction
MSH2	PMS2	string_interaction
MSH2	POLE	string_interaction
MSH2	RAD51D	string_interaction
PMS2	POLE	string_interaction

Structural data

PDB: 10 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHEK2	O96017	38
APC	P25054	31
MSH2	P43246	30
DICER1	Q9UPY3	21
POLE	Q07864	18
RAD51D	O75771	17
BRCA2	P51587	14
ATM	Q13315	14
PMS2	P54278	9
SDHA	P31040	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 124. Enrichment computed across 10 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
HDR through Homologous Recombination (HRR)	4	76.1×	1e-05	BRCA2, ATM, POLE, RAD51D
TP53 Regulates Transcription of DNA Repair Genes	4	72.5×	1e-05	MSH2, ATM, PMS2, RAD51D
Diseases of DNA repair	3	171.3×	2e-05	BRCA2, MSH2, ATM
Impaired BRCA2 binding to PALB2	3	137.0×	2e-05	BRCA2, ATM, RAD51D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	3	126.9×	2e-05	BRCA2, ATM, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	3	126.9×	2e-05	BRCA2, ATM, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	3	126.9×	2e-05	BRCA2, ATM, RAD51D
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	3	118.1×	3e-05	BRCA2, ATM, RAD51D
Homologous DNA Pairing and Strand Exchange	3	114.2×	3e-05	BRCA2, ATM, RAD51D
Resolution of D-loop Structures through Holliday Junction Intermediates	3	90.2×	5e-05	BRCA2, ATM, RAD51D
Presynaptic phase of homologous DNA pairing and strand exchange	3	81.6×	6e-05	BRCA2, ATM, RAD51D
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	190.3×	5e-04	BRCA2, ATM
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	2	163.1×	5e-04	MSH2, PMS2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	2	163.1×	5e-04	MSH2, PMS2
Diseases of DNA Double-Strand Break Repair	2	163.1×	5e-04	BRCA2, ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2	163.1×	5e-04	BRCA2, ATM
Stabilization of p53	2	152.3×	5e-04	CHEK2, ATM
Resolution of D-Loop Structures	2	126.9×	7e-04	BRCA2, ATM
DNA Repair	3	29.5×	8e-04	BRCA2, MSH2, ATM
Regulation of TP53 Activity through Methylation	2	108.8×	9e-04	CHEK2, ATM
Homology Directed Repair	2	61.7×	0.002	BRCA2, ATM
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2	61.7×	0.002	BRCA2, ATM
Impaired BRCA2 binding to RAD51	2	61.7×	0.002	BRCA2, ATM
Regulation of TP53 Degradation	2	58.6×	0.003	CHEK2, ATM
Meiosis	2	57.1×	0.003	BRCA2, ATM
DNA Double-Strand Break Repair	2	49.6×	0.003	BRCA2, ATM
APC truncation mutants are not K63 polyubiquitinated	1	1142.0×	0.004	APC
Reproduction	2	38.1×	0.005	BRCA2, ATM
Defective Mismatch Repair Associated With MLH1	1	571.0×	0.007	PMS2
Defective Mismatch Repair Associated With MSH3	1	571.0×	0.007	MSH2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
double-strand break repair	4	81.2×	2e-05	BRCA2, CHEK2, MSH2, ATM
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	3	148.7×	8e-05	BRCA2, CHEK2, MSH2
somatic recombination of immunoglobulin gene segments	2	842.6×	1e-04	MSH2, PMS2
DNA damage response, signal transduction by p53 class mediator	3	107.6×	1e-04	BRCA2, CHEK2, ATM
positive regulation of isotype switching to IgA isotypes	2	561.7×	2e-04	MSH2, PMS2
telomere maintenance via recombination	2	306.4×	5e-04	BRCA2, RAD51D
positive regulation of isotype switching to IgG isotypes	2	306.4×	5e-04	MSH2, PMS2
regulation of autophagosome assembly	2	224.7×	7e-04	CHEK2, ATM
double-strand break repair via homologous recombination	3	46.8×	7e-04	BRCA2, ATM, RAD51D
somatic hypermutation of immunoglobulin genes	2	210.7×	7e-04	MSH2, PMS2
replicative senescence	2	198.3×	7e-04	CHEK2, ATM
mitotic intra-S DNA damage checkpoint signaling	2	187.2×	7e-04	CHEK2, MSH2
response to X-ray	2	177.4×	8e-04	BRCA2, MSH2
cellular response to stress	2	168.5×	8e-04	CHEK2, ATM
signal transduction in response to DNA damage	2	160.5×	8e-04	CHEK2, ATM
mismatch repair	2	129.6×	0.001	MSH2, PMS2
cellular response to gamma radiation	2	120.4×	0.001	CHEK2, ATM
mitotic spindle assembly checkpoint signaling	2	112.3×	0.001	APC, ATM
reciprocal meiotic recombination	2	112.3×	0.001	ATM, RAD51D
determination of adult lifespan	2	86.4×	0.002	MSH2, ATM
DNA damage checkpoint signaling	2	78.4×	0.002	CHEK2, ATM
regulation of signal transduction by p53 class mediator	2	76.6×	0.002	CHEK2, ATM
intrinsic apoptotic signaling pathway in response to DNA damage	2	64.8×	0.003	CHEK2, ATM
cellular senescence	2	59.1×	0.004	BRCA2, ATM
somatic recombination of immunoglobulin genes involved in immune response	1	1685.2×	0.004	MSH2
telomere maintenance	2	53.5×	0.004	ATM, RAD51D
DNA damage response	3	16.1×	0.005	CHEK2, APC, ATM
positive regulation of Schwann cell differentiation	1	842.6×	0.007	DICER1
establishment of RNA localization to telomere	1	842.6×	0.007	ATM
establishment of protein-containing complex localization to telomere	1	842.6×	0.007	ATM

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 7

Druggability breadth: 8 of 10 evidence-associated genes (80%) 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
SDHA	LINEZOLID
CHEK2	NERATINIB
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATM	35	4
CHEK2	30	4
SDHA	1	4
BRCA2	0	0
DICER1	0	0
APC	0	0
MSH2	0	0
PMS2	0	0
POLE	0	0
RAD51D	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LINEZOLID	4	SDHA
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2
GEFITINIB	4	CHEK2
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
DOVITINIB	3	CHEK2
LESTAURTINIB	3	CHEK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
CHEK2	690	Binding:687, Functional:2, ADMET:1
ATM	240	Binding:233, Functional:5, ADMET:2
APC	24	Binding:24
MSH2	9	Binding:9
DICER1	8	Binding:8
SDHA	3	Binding:3
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
DICER1	3.1.26.3	ribonuclease III
ATM	2.7.11.1	non-specific serine/threonine protein kinase
POLE	2.7.7.7	DNA-directed DNA polymerase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHEK2	690
ATM	240

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

29 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)
LINEZOLID	4	SDHA
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2
GEFITINIB	4	CHEK2
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
FASUDIL	3	CHEK2
CEDIRANIB	3	CHEK2
DOVITINIB	3	CHEK2
LESTAURTINIB	3	CHEK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	SDHA, CHEK2, ATM
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	DICER1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	6	BRCA2, APC, MSH2, PMS2, POLE, RAD51D

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	—
DICER1	8	—
APC	24	—
MSH2	9	—
PMS2	1	—
POLE	0	—
RAD51D	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,248.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	500
Not specified	285
PHASE2	138
PHASE1/PHASE2	80
PHASE3	52
PHASE4	26
EARLY_PHASE1	13
PHASE2/PHASE3	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT06706921	PHASE4	RECRUITING	18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With Prostate Cancer
NCT00050635	PHASE4	COMPLETED	STOP Trial - Sandostatin LAR Depot Trial for the Optimum Prevention of Chemotherapy Induced Diarrhea
NCT00117039	PHASE4	COMPLETED	A Study to Evaluate the Effectiveness of Aranesp® for Cancer Patients With Anemia
NCT00216541	PHASE4	COMPLETED	A Study of the Safety and Effectiveness of Epoetin Alfa on Hemoglobin Levels and Blood Transfusions in Cancer Patients Receiving Chemotherapy
NCT00283465	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Treatment With Epoetin Alfa on Hemoglobin Levels, Red Blood Cell Transfusions, and Quality of Life in Patients With Cancer Receiving Platinum-containing Chemotherapy
NCT00630084	PHASE4	COMPLETED	Peginterferon Plus Ribavirin for Hepatitis C Patients Concomitant With Malignancy Other Than Hepatocellular Carcinoma
NCT00684463	PHASE4	COMPLETED	Palonosetron in Moderately and Highly Emetogenic Chemotherapy Induced Nausea and Vomiting (Study P04935)(COMPLETED)
NCT00687011	PHASE4	COMPLETED	Palonosetron Plus Dexamethasone in Moderately Emetogenic Chemotherapy Induced Nausea and Vomiting (Study P04594)
NCT00894153	PHASE4	UNKNOWN	p53 Gene Therapy for Head and Neck Malignant Tumors in Advanced Stage
NCT01394991	PHASE4	COMPLETED	A Safety Study of Epoetin Alfa in Patients With Cancer Who Have Chemotherapy-Related Anemia
NCT01427400	PHASE4	UNKNOWN	The Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01481831	PHASE4	COMPLETED	Efficacy and Safety of Palonosetron Hydrochloride in the Prevention of Nausea and Vomiting
NCT01588184	PHASE4	COMPLETED	An Extension Study to Provide Continued Bevacizumab Therapy to Participants With Solid Tumors Who Were Previously Enrolled in a Roche/Genentech Sponsored Study
NCT01708850	PHASE4	COMPLETED	Study in Cancer Patients With Central Line Associated Clots in the Upper Extremity Treated With Rivaroxaban (Catheter 2)
NCT01739764	PHASE4	COMPLETED	An Extension (Rollover) Study of Vemurafenib in Participants With BRAF V600 Mutation-Positive Malignancies Previously Enrolled in an Antecedent Vemurafenib Protocol
NCT01789281	PHASE4	COMPLETED	Everolimus Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Everolimus Study.
NCT01802996	PHASE4	UNKNOWN	Evaluate the Efficacy of Magnesium Isoglycyrrhizinate in the Prevention of Chemotherapy Related Acute Liver Injury
NCT01862198	PHASE4	COMPLETED	The Usefulness of Endoscopic Ultrasound-guided Biliary Drainage With a Newly Designed Hybrid Metallic Stent
NCT01894828	PHASE4	UNKNOWN	Nutritional Supplementation in Patients With no Signs of Malnutrition
NCT02581176	PHASE4	COMPLETED	Apixaban as Treatment of Venous Thrombosis in Patients With Cancer: The CAP Study
NCT03333655	PHASE4	COMPLETED	Study to Explore the Mechanism of Acquired Immune Escape In Participants With Metastatic Cancer Progressing on CPI Therapy
NCT03895502	PHASE4	COMPLETED	Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study
NCT04724460	PHASE4	COMPLETED	Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer
NCT06005259	PHASE4	UNKNOWN	Effect of Spironolactone in the Prevention of Anthracycline-induced Cardiotoxicity (SPIROTOX)
NCT03194893	PHASE3	ACTIVE_NOT_RECRUITING	A Rollover Study of Alectinib in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive or Rearranged During Transfection (RET)-Positive Cancer
NCT03435796	PHASE2/PHASE3	RECRUITING	Long-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells
NCT03961841	PHASE3	NOT_YET_RECRUITING	Perioperative Combination Chemotherapy Versus Chemoradiation for Locally Advanced EGJ Adenocarcinoma
NCT03981796	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer
NCT04607421	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
NCT04711109	PHASE3	ACTIVE_NOT_RECRUITING	Studying the Effect of Denosumab on Preventing Breast Cancer in Women With a BRCA1 Germline Mutation
NCT05112965	PHASE3	ACTIVE_NOT_RECRUITING	An Extension Study in Participants Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (IMbrella C)
NCT06496971	PHASE3	RECRUITING	A Prospective Pivotal Study to Evaluate the Efficacy and Safety of Avastin® Bevacizumab (BEV) With or Without Microbubble-mediated Focused Ultrasound (FUS-MB) Using NaviFUS System in Recurrent Glioblastoma Multiforme Patients
NCT06672887	PHASE2/PHASE3	RECRUITING	Enhancing Successful Return to Work of Employees With Cancer, by Supporting Employers (MiLES Intervention)
NCT00034879	PHASE3	COMPLETED	Iressa Expanded Access Program (EAP)
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00038064	PHASE3	COMPLETED	Anemia in Patients With a Non-Myeloid Malignancy
NCT00124930	PHASE3	TERMINATED	Study Comparing Olanzapine With Haloperidol for the Relief of Nausea and Vomiting in Patients With Advanced Cancer
NCT00125801	PHASE3	TERMINATED	The Pain Pen for Breakthrough Cancer Pain

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOSTARLIMAB	4	15
EPOETIN ALFA	4	14
DACOMITINIB ANHYDROUS	4	10
DOXORUBICIN	4	10
NIRAPARIB	4	7
ALECTINIB	4	5
VEMURAFENIB	4	5
COBIMETINIB	4	4
IRINOTECAN	4	4
PALONOSETRON	4	4
TEPROTUMUMAB	4	4
BELANTAMAB MAFODOTIN	4	3
ERDAFITINIB	4	3
ISATUXIMAB	4	3
RUCAPARIB	4	3
TRABECTEDIN	4	3
VISMODEGIB	4	3
AFATINIB	4	2
ALPELISIB	4	2
AXITINIB	4	2
CRIZOTINIB	4	2
EDOXABAN	4	2
ESCITALOPRAM	4	2
GLUCARPIDASE	4	2
INDOCYANINE GREEN	4	2
IXABEPILONE	4	2
LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN	4	2
MIRTAZAPINE	4	2
MITOMYCIN	4	2
NERATINIB	4	2