Breast neoplasm

disease

On this page

Also known as breast neoplasm (disease)breast tumorbreast tumourneoplasm of breastneoplasm of the breastneoplasm, breasttumor of breasttumor of the breasttumour of breasttumour of the breast

Summary

Breast neoplasm (MONDO:0021100) is a cancer (an umbrella term covering 11 Mondo subtypes) with 19 cohort genes (11 GWAS associations across 25 studies; 14 CIViC-evidence somatic drivers; 287 ClinVar predisposition records) and 1,180 clinical trials. The dominant Reactome pathway is Resolution of D-loop Structures through Holliday Junction Intermediates (7 cohort genes). Top therapeutic interventions include tamoxifen, letrozole, and docetaxel anhydrous.

At a glance

Classification: Cancer
Umbrella term: 11 Mondo subtypes
Cohort genes: 19
GWAS associations: 11
ClinVar variants: 287
Clinical trials: 1,180

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	breast neoplasm
Mondo ID	MONDO:0021100
EFO	EFO:0003869
MeSH	D001943
NCIT	C2910
SNOMED CT	126926005
UMLS	C1458155
MedGen	264172
Anatomy (UBERON)	UBERON:0000310
Is cancer (heuristic)	yes

Also known as: breast neoplasm · breast neoplasm (disease) · breast tumor · breast tumour · neoplasm of breast · neoplasm of the breast · neoplasm, breast · tumor of breast · tumor of the breast · tumour of breast · tumour of the breast

Data availability: 287 ClinVar variants · 11 GWAS associations (25 studies).

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › breast disorder › breast neoplasm

Related subtypes (14): breast abscess, hypertrophy of breast, fat necrosis of breast, breast angiomatosis, breast adenosis, benign mammary dysplasia, breast fibrocystic disease, mastitis, familial juvenile hypertrophy of the breast, supernumerary breasts, isolated congenital breast hypoplasia/aplasia, syndromic breast hypoplasia/aplasia, lactation disease, breast implant illness

Subtypes (11): breast benign neoplasm, nipple neoplasm, breast myoepithelial tumor, breast neuroendocrine neoplasm, breast granular cell tumor, intraductal breast neoplasm, breast hemangiopericytoma, breast fibrosis, breast cancer, benign ductal tumor of breast, breast fibroepithelial neoplasm

Genetics & variants

GWAS landscape

11 GWAS associations across 25 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs62235681	2e-14	TTC28 - CHEK2	G	0.74
rs62237617	1e-10	TTC28	T	1.59
chr2:132720718	2e-09		T	3.25
chr10:62528371	5e-09		C	0.1
chr11:88449878	2e-08		A	2.04
chr13:76105491	2e-08		A	2.76
chr11:80734749	3e-08		A	2.57
chr16:78354953	3e-08		A	0.2
chr5:158793484	3e-08		G	0.07
chr3:88222367	5e-08		C	0.1
rs147535182	9e-07	AK8	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90474221	UK Biobank Whole-Genome Sequencing Consortium	2025	15,125	443,315	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667937	UK Biobank Whole-Genome Sequencing Consortium	2025	15,125	443,315	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90041833	Jiang L	2021	10,971	445,377	A generalized linear mixed model association tool for biobank-scale data.
GCST90081349	Backman JD	2021	8,566	379,356	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085335	Backman JD	2021	8,566	379,356	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90478666	Verma A	2024	7,692	436,291	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080641	Backman JD	2021	6,317	195,686	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084627	Backman JD	2021	6,317	195,686	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90043889	Jiang L	2021	6,087	450,261	A generalized linear mixed model association tool for biobank-scale data.
GCST90478665	Verma A	2024	3,384	115,618	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	11

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	2
unknown	9

Functional consequences

Consequence	Count
unknown	8
intron_variant	2
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs62235681	22	28684743	A>G	0.006	intergenic_variant	TTC28 - CHEK2	2e-14	Tier 4: intronic/intergenic
rs62237617	22	28365160	C>G,T	0.002	intron_variant	TTC28	1e-10	Tier 4: intronic/intergenic
chr2:132720718							2e-09	Tier 4: intronic/intergenic
chr10:62528371							5e-09	Tier 4: intronic/intergenic
chr11:88449878							2e-08	Tier 4: intronic/intergenic
chr13:76105491							2e-08	Tier 4: intronic/intergenic
chr11:80734749							3e-08	Tier 4: intronic/intergenic
chr16:78354953							3e-08	Tier 4: intronic/intergenic
chr5:158793484							3e-08	Tier 4: intronic/intergenic
chr3:88222367							5e-08	Tier 4: intronic/intergenic
rs147535182	9	132754462	T>A		intron_variant	AK8	9e-07	Tier 4: intronic/intergenic

ClinVar germline variants

287 retrieved; paginated sample, class counts are floors:

119 pathogenic, 79 conflicting classifications of pathogenicity, 39 benign, 15 uncertain significance, 13 likely benign, 12 pathogenic/likely pathogenic, 7 benign/likely benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic/pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3019	NM_000051.4(ATM):c.7638_7646del (p.Arg2547_Ser2549del)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3023	NM_000051.4(ATM):c.7271T>G (p.Val2424Gly)	ATM	Pathogenic	reviewed by expert panel
430593	NM_000051.4(ATM):c.6312G>A (p.Trp2104Ter)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
430590	NM_000465.4(BARD1):c.654G>A (p.Trp218Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17661	NM_007294.4(BRCA1):c.181T>G (p.Cys61Gly)	BRCA1	Pathogenic	reviewed by expert panel
17671	NM_007294.4(BRCA1):c.3607C>T (p.Arg1203Ter)	BRCA1	Pathogenic	reviewed by expert panel
17677	NM_007294.4(BRCA1):c.5266dup (p.Gln1756fs)	BRCA1	Pathogenic	reviewed by expert panel
224416	NM_007294.4(BRCA1):c.81_134del (p.Cys27_Lys45delinsTer)	BRCA1	Pathogenic	reviewed by expert panel
224417	NM_007294.4(BRCA1):c.519del (p.Gln174fs)	BRCA1	Pathogenic	reviewed by expert panel
224418	NM_007294.4(BRCA1):c.3819_3823del (p.Gln1273fs)	BRCA1	Pathogenic	reviewed by expert panel
224419	NM_007294.4(BRCA1):c.1299dup (p.Ser434fs)	BRCA1	Pathogenic	reviewed by expert panel
224420	NM_007294.4(BRCA1):c.2556_2557insTTCACTTTTC (p.Asp853fs)	BRCA1	Pathogenic	criteria provided, single submitter
224421	NM_007294.4(BRCA1):c.2570T>A (p.Leu857Ter)	BRCA1	Pathogenic	reviewed by expert panel
224422	NM_007294.4(BRCA1):c.4069_4070insTTGA (p.Glu1357fs)	BRCA1	Pathogenic	criteria provided, single submitter
224423	NM_007294.4(BRCA1):c.4755del (p.Glu1586fs)	BRCA1	Pathogenic	criteria provided, single submitter
224424	NM_007294.4(BRCA1):c.4712del (p.Phe1571fs)	BRCA1	Pathogenic	reviewed by expert panel
224425	NM_007294.4(BRCA1):c.4677_5075del (p.Glu1559_Thr1691del)	BRCA1	Pathogenic	criteria provided, single submitter
224426	NM_007294.4(BRCA1):c.213-2A>G	BRCA1	Pathogenic	criteria provided, multiple submitters, no conflicts
224427	NM_007294.4(BRCA1):c.192T>G (p.Cys64Trp)	BRCA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
266349	NM_007294.4(BRCA1):c.3266del (p.Leu1089fs)	BRCA1	Pathogenic	reviewed by expert panel
371936	NM_007294.4(BRCA1):c.5156del (p.Val1719fs)	BRCA1	Pathogenic	criteria provided, multiple submitters, no conflicts
373823	NM_007294.4(BRCA1):c.5463_5464insT (p.His1822fs)	BRCA1	Pathogenic	reviewed by expert panel
37392	NM_007294.4(BRCA1):c.116G>A (p.Cys39Tyr)	BRCA1	Pathogenic	criteria provided, multiple submitters, no conflicts
37438	NM_007294.4(BRCA1):c.1961del (p.Lys654fs)	BRCA1	Pathogenic	reviewed by expert panel
37523	NM_007294.4(BRCA1):c.3331_3334del (p.Gln1111fs)	BRCA1	Pathogenic	reviewed by expert panel
37570	NM_007294.4(BRCA1):c.4120_4121del (p.Glu1373_Ser1374insTer)	BRCA1	Pathogenic	reviewed by expert panel
37623	NM_007294.4(BRCA1):c.5030_5033del (p.Thr1677fs)	BRCA1	Pathogenic	reviewed by expert panel
37691	NM_007294.4(BRCA1):c.66dup (p.Glu23fs)	BRCA1	Pathogenic	reviewed by expert panel
417831	NM_007294.4(BRCA1):c.3644_3648del (p.Asn1215fs)	BRCA1	Pathogenic	reviewed by expert panel
430589	Single allele	BRCA1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 98 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
CHEK2	Act	BRCA	CIViC #8950
DICER1	LoF	COADREAD,CSCC,MEL,UCEC	CIViC #9533
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888
BRIP1			CIViC #15955
PALB2	LoF	OVT	CIViC #15013
IL7R	Act	ALL,ESCA,HCC,STAD	CIViC #2975
JUN			CIViC #3094
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
BARD1	Act	PRAD	CIViC #549
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
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

Cohort genes → proteins

19 cohort genes, 19 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	19

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
DICER1	HGNC:17098	ENSG00000100697	Q9UPY3	Endoribonuclease Dicer	clinvar
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	clinvar
CKS1B	HGNC:19083	ENSG00000173207	P61024	Cyclin-dependent kinases regulatory subunit 1	clinvar
GALNT12	HGNC:19877	ENSG00000119514	Q8IXK2	Polypeptide N-acetylgalactosaminyltransferase 12	clinvar
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
GEN1	HGNC:26881	ENSG00000178295	Q17RS7	Flap endonuclease GEN homolog 1	clinvar
IL2	HGNC:6001	ENSG00000109471	P60568	Interleukin-2	clinvar
IL7R	HGNC:6024	ENSG00000168685	P16871	Interleukin-7 receptor subunit alpha	clinvar
JUN	HGNC:6204	ENSG00000177606	P05412	Transcription factor Jun	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	clinvar
BARD1	HGNC:952	ENSG00000138376	Q99728	BRCA1-associated RING domain protein 1	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
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.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
CKS1B	Cyclin-dependent kinases regulatory subunit 1	Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.
GALNT12	Polypeptide N-acetylgalactosaminyltransferase 12	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
GEN1	Flap endonuclease GEN homolog 1	Endonuclease which resolves Holliday junctions (HJs) by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated.
IL2	Interleukin-2	Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance.
IL7R	Interleukin-7 receptor subunit alpha	Receptor for interleukin-7.
JUN	Transcription factor Jun	Transcription factor that recognizes and binds to the AP-1 consensus motif 5’-TGA[GC]TCA-3’.
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).
BARD1	BRCA1-associated RING domain protein 1	E3 ubiquitin-protein ligase.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 10 · Difficult: 5 · Unknown: 4 · Druggable fraction: 0.53

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	3	4.4×	0.236
Enzyme (other)	4	2.5×	0.272
Phosphatase	1	4.4×	0.349
Transporter	1	4.1×	0.349
Transcription factor	4	1.7×	0.349
Antibody/Immunoglobulin	1	1.5×	0.646
Scaffold/PPI	1	0.9×	0.775
Other/Unknown	4	0.4×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
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
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
CKS1B	Kinase	yes		Cyclin-dep_kinase_reg-sub, Cyclin-dep_kinase_reg-sub_sf
GALNT12	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
GEN1	Enzyme (other)	yes	3.1.21.10	XPG/Rad2, XPG_DNA_repair_N, XPG-I_dom
IL2	Other/Unknown	no		IL-2, 4_helix_cytokine-like_core, IL-2_CS
IL7R	Antibody/Immunoglobulin	yes		Hempt_rcpt_S_F1_CS, FN3_dom, Ig-like_fold
JUN	Transcription factor	no		Leuzip_Jun, bZIP, JNK
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
BARD1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, Ankyrin_rpt
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

Expression context

Cohort genes with no expression data: 0.

17 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)	19
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	7
primordial germ cell in gonad	5
ventricular zone	5
secondary oocyte	3
ganglionic eminence	2
tongue squamous epithelium	2
lymph node	2
buccal mucosa cell	2
oocyte	2
calcaneal tendon	2
tendon of biceps brachii	1
lower esophagus mucosa	1
caput epididymis	1
cauda epididymis	1
esophagus squamous epithelium	1
gingival epithelium	1
jejunal mucosa	1
body of pancreas	1
gall bladder	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
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
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium
CFTR	193	broad	marker	body of pancreas, gall bladder, pancreas
CKS1B	141	ubiquitous	marker	ventricular zone, ganglionic eminence, lymph node
GALNT12	232	ubiquitous	marker	palpebral conjunctiva, mucosa of sigmoid colon, corpus epididymis
BRIP1	181	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
GEN1	228	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, primordial germ cell in gonad
IL2	92		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell
IL7R	220	ubiquitous	marker	right lung, granulocyte, lymph node
JUN	290	ubiquitous	marker	vena cava, mucosa of stomach, cardia of stomach
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
BARD1	271	ubiquitous	marker	secondary oocyte, oocyte, tongue squamous epithelium
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 32.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
JUN	12,228
PTEN	11,626
BRCA1	9,064
CDH1	8,738
DICER1	8,268
CFTR	7,664
ATM	7,383
PALB2	5,641
BRCA2	4,839

Intra-cohort edges

A	B	Sources
ATM	BARD1	string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BARD1	BRCA1	biogrid_interaction, intact, string_interaction
BARD1	BRCA2	string_interaction
BARD1	BRIP1	biogrid_interaction
BARD1	CHEK2	string_interaction
BARD1	PALB2	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	BRIP1	biogrid_interaction, intact, string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	PMS2	string_interaction
BRCA1	TP53	string_interaction
BRCA2	BRIP1	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	GEN1	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	PMS2	string_interaction
BRCA2	TP53	string_interaction
BRIP1	PALB2	string_interaction
BRIP1	PMS2	biogrid_interaction, intact
CDH1	CFTR	intact
CDH1	GALNT12	intact
CDH1	PTEN	string_interaction
CHEK2	PALB2	string_interaction
CHEK2	TP53	intact, string_interaction
GALNT12	PMS2	intact, string_interaction
JUN	TP53	string_interaction
PTEN	TP53	string_interaction

Structural data

PDB: 19 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
CFTR	P13569	58
CHEK2	O96017	38
IL2	P60568	37
BRCA1	P38398	33
CDH1	P12830	22
DICER1	Q9UPY3	21
CKS1B	P61024	19
BRCA2	P51587	14
ATM	Q13315	14
PTEN	P60484	12
BARD1	Q99728	11
JUN	P05412	10
PMS2	P54278	9
IL7R	P16871	8
PALB2	Q86YC2	4
BRIP1	Q9BX63	3
GALNT12	Q8IXK2	1
GEN1	Q17RS7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 247. Enrichment computed across 19 evidence-associated genes (19 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 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Resolution of D-loop Structures through Holliday Junction Intermediates	7	110.7×	3e-11	BRCA1, BRCA2, BRIP1, PALB2, GEN1, ATM, BARD1
Impaired BRCA2 binding to PALB2	6	144.2×	1e-10	BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	6	133.6×	1e-10	BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	6	133.6×	1e-10	BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	6	133.6×	1e-10	BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	6	124.4×	2e-10	BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1
Homologous DNA Pairing and Strand Exchange	6	120.2×	2e-10	BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1
HDR through Homologous Recombination (HRR)	6	60.1×	1e-08	BRCA1, BRCA2, BRIP1, PALB2, ATM, BARD1
Defective homologous recombination repair (HRR) due to PALB2 loss of function	4	200.3×	7e-08	BRCA1, BRCA2, ATM, BARD1
Impaired BRCA2 binding to RAD51	5	81.2×	7e-08	BRCA1, BRCA2, BRIP1, ATM, BARD1
Diseases of DNA Double-Strand Break Repair	4	171.7×	1e-07	BRCA1, BRCA2, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	4	171.7×	1e-07	BRCA1, BRCA2, ATM, BARD1
Presynaptic phase of homologous DNA pairing and strand exchange	5	71.5×	1e-07	BRCA1, BRCA2, BRIP1, ATM, BARD1
G2/M DNA damage checkpoint	6	38.0×	1e-07	BRCA1, TP53, CHEK2, BRIP1, ATM, BARD1
Regulation of TP53 Activity through Phosphorylation	6	37.2×	1e-07	BRCA1, TP53, CHEK2, BRIP1, ATM, BARD1
Resolution of D-Loop Structures	4	133.6×	3e-07	BRCA1, BRCA2, ATM, BARD1
Diseases of DNA repair	4	120.2×	4e-07	BRCA1, BRCA2, ATM, BARD1
TP53 Regulates Transcription of DNA Repair Genes	5	47.7×	7e-07	BRCA1, TP53, JUN, ATM, PMS2
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	5	38.5×	2e-06	BRCA1, TP53, CHEK2, ATM, BARD1
Homology Directed Repair	4	65.0×	4e-06	BRCA1, BRCA2, ATM, BARD1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	4	65.0×	4e-06	BRCA1, BRCA2, ATM, BARD1
HDR through Single Strand Annealing (SSA)	4	61.6×	5e-06	BRCA1, BRIP1, ATM, BARD1
DNA Double-Strand Break Repair	4	52.3×	9e-06	BRCA1, BRCA2, ATM, BARD1
Stabilization of p53	3	120.2×	2e-05	TP53, CHEK2, ATM
Defective DNA double strand break response due to BRCA1 loss of function	2	601.0×	2e-05	BRCA1, BARD1
Defective DNA double strand break response due to BARD1 loss of function	2	601.0×	2e-05	BRCA1, BARD1
Regulation of TP53 Activity through Methylation	3	85.9×	5e-05	TP53, CHEK2, ATM
DNA Double Strand Break Response	3	75.1×	7e-05	BRCA1, ATM, BARD1
G2/M Checkpoints	4	28.3×	9e-05	BRCA1, TP53, ATM, BARD1
Processing of DNA double-strand break ends	4	24.0×	2e-04	BRCA1, BRIP1, ATM, BARD1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
double-strand break repair	6	64.1×	1e-07	BRCA1, BRCA2, TP53, CHEK2, BRIP1, ATM
cellular response to ionizing radiation	4	86.5×	2e-05	BRCA1, BRCA2, TP53, BARD1
double-strand break repair via homologous recombination	5	41.1×	2e-05	BRCA1, BRCA2, PALB2, GEN1, ATM
DNA damage response, signal transduction by p53 class mediator	4	75.5×	2e-05	BRCA2, TP53, CHEK2, ATM
homologous recombination	3	221.7×	2e-05	BRCA1, BRIP1, BARD1
regulation of DNA damage checkpoint	3	177.4×	4e-05	BRCA1, BRCA2, BARD1
replicative senescence	3	156.5×	5e-05	TP53, CHEK2, ATM
cellular response to gamma radiation	3	95.0×	2e-04	TP53, CHEK2, ATM
regulation of cell cycle	5	19.6×	2e-04	BRCA1, TP53, JUN, ATM, BARD1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	3	78.3×	3e-04	BRCA2, TP53, CHEK2
cellular response to indole-3-methanol	2	354.8×	5e-04	BRCA1, CDH1
DNA damage checkpoint signaling	3	61.9×	5e-04	CHEK2, BRIP1, ATM
nucleotide-excision repair	3	60.5×	5e-04	BRCA2, TP53, BRIP1
somitogenesis	3	59.1×	5e-04	TP53, PALB2, ATM
DNA damage response	5	14.1×	6e-04	BRCA1, TP53, CHEK2, ATM, BARD1
intrinsic apoptotic signaling pathway in response to DNA damage	3	51.2×	7e-04	BRCA1, CHEK2, ATM
DNA strand resection involved in replication fork processing	2	221.7×	8e-04	BRCA1, BARD1
cellular senescence	3	46.7×	8e-04	BRCA2, TP53, ATM
positive regulation of DNA-templated transcription	6	8.8×	9e-04	BRCA1, BRCA2, TP53, CHEK2, CDH1, JUN
positive regulation of isotype switching to IgG isotypes	2	161.3×	0.001	IL2, PMS2
thymocyte apoptotic process	2	147.8×	0.002	TP53, CHEK2
regulation of autophagosome assembly	2	118.3×	0.003	CHEK2, ATM
inner cell mass cell proliferation	2	104.3×	0.003	BRCA2, PALB2
protein K6-linked ubiquitination	2	104.3×	0.003	BRCA1, BARD1
protein stabilization	4	14.1×	0.003	TP53, CHEK2, ATM, PTEN
negative regulation of reactive oxygen species metabolic process	2	98.5×	0.003	BRCA1, TP53
response to X-ray	2	93.4×	0.003	BRCA2, TP53
cellular response to stress	2	88.7×	0.004	CHEK2, ATM
signal transduction in response to DNA damage	2	84.5×	0.004	CHEK2, ATM
mitotic G2/M transition checkpoint	2	84.5×	0.004	BRCA1, BARD1

Therapeutics

Drugs indicated for this disease

32 approved, 156 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Abemaciclib	Approved (phase 4)
Alpelisib	Approved (phase 4)
Anastrozole	Approved (phase 4)
Atezolizumab	Approved (phase 4)
Bevacizumab	Approved (phase 4)
Capecitabine	Approved (phase 4)
Capivasertib	Approved (phase 4)
Denosumab	Approved (phase 4)
Docetaxel Anhydrous	Approved (phase 4)
Estradiol	Approved (phase 4)
Estrogens, Conjugated	Approved (phase 4)
Estrogens, Esterified	Approved (phase 4)
Everolimus	Approved (phase 4)
Exemestane	Approved (phase 4)
Fulvestrant	Approved (phase 4)
Inavolisib	Approved (phase 4)
Ixabepilone	Approved (phase 4)
Letrozole	Approved (phase 4)
Margetuximab	Approved (phase 4)
Methotrexate	Approved (phase 4)
Methyltestosterone	Approved (phase 4)
Olaparib	Approved (phase 4)
Paclitaxel	Approved (phase 4)
Palbociclib	Approved (phase 4)
Pertuzumab	Approved (phase 4)
Sacituzumab Govitecan	Approved (phase 4)
TECHNETIUM TC 99M SULFUR COLLOID	Approved (phase 4)
TECHNETIUM TC 99M TILMANOCEPT	Approved (phase 4)
Trastuzumab	Approved (phase 4)
Trastuzumab Deruxtecan	Approved (phase 4)
Trastuzumab Emtansine	Approved (phase 4)
Tucatinib	Approved (phase 4)
Abiraterone Acetate	Phase 3 (in late-stage trials)
Adagloxad Simolenin	Phase 3 (in late-stage trials)
Afatinib	Phase 3 (in late-stage trials)
Afuresertib	Phase 3 (in late-stage trials)
Albumin Human	Phase 3 (in late-stage trials)
Aldesleukin	Phase 3 (in late-stage trials)
Amcenestrant	Phase 3 (in late-stage trials)
Aminoglutethimide	Phase 3 (in late-stage trials)
Arzoxifene	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atamestane	Phase 3 (in late-stage trials)
Atorvastatin	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Balixafortide	Phase 3 (in late-stage trials)
Belladonna	Phase 3 (in late-stage trials)
Bicalutamide	Phase 3 (in late-stage trials)
Buparlisib	Phase 3 (in late-stage trials)
Bupivacaine	Phase 3 (in late-stage trials)
Busulfan	Phase 3 (in late-stage trials)
Calcium	Phase 3 (in late-stage trials)
Camizestrant	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Candesartan Cilexetil	Phase 3 (in late-stage trials)
Cannabidiol	Phase 3 (in late-stage trials)
Capsaicin	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Carmustine	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Ciprofloxacin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Clindamycin	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Cytarabine	Phase 3 (in late-stage trials)
Dalpiciclib	Phase 3 (in late-stage trials)
Dalteparin Sodium	Phase 3 (in late-stage trials)
Darbepoetin Alfa	Phase 3 (in late-stage trials)
Datopotamab Deruxtecan	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Dextrose	Phase 3 (in late-stage trials)
Disitamab Vedotin	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Efaproxiral	Phase 3 (in late-stage trials)
Efbemalenograstim Alfa	Phase 3 (in late-stage trials)
Elacestrant	Phase 3 (in late-stage trials)
Endostatin, N-Terminal-Mggshhhhh	Phase 3 (in late-stage trials)
Enobosarm	Phase 3 (in late-stage trials)
Entinostat	Phase 3 (in late-stage trials)
Enzalutamide	Phase 3 (in late-stage trials)
Epirubicin	Phase 3 (in late-stage trials)
Epoetin Alfa	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Eribulin	Phase 3 (in late-stage trials)
Estrogen	Phase 3 (in late-stage trials)
Ethinyl Estradiol	Phase 3 (in late-stage trials)
Etirinotecan Pegol	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Fenretinide	Phase 3 (in late-stage trials)
Fibrin	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Fluzoparib	Phase 3 (in late-stage trials)
Gedatolisib	Phase 3 (in late-stage trials)
Gefitinib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Gentamicin	Phase 3 (in late-stage trials)
Giredestrant	Phase 3 (in late-stage trials)
Gonadotropin, Chorionic	Phase 3 (in late-stage trials)
Goserelin	Phase 3 (in late-stage trials)
HEMAY-022	Phase 3 (in late-stage trials)
INTERFERON GAMMA-1B	Phase 3 (in late-stage trials)
Ibandronic Acid	Phase 3 (in late-stage trials)
Ibuprofen	Phase 3 (in late-stage trials)
Imlunestrant	Phase 3 (in late-stage trials)
Iniparib	Phase 3 (in late-stage trials)
Ipatasertib	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Isoflavone	Phase 3 (in late-stage trials)
Isotretinoin	Phase 3 (in late-stage trials)
KN-026	Phase 3 (in late-stage trials)
Ketorolac	Phase 3 (in late-stage trials)
Keyhole Limpet Hemocyanin	Phase 3 (in late-stage trials)
Lansoprazole	Phase 3 (in late-stage trials)
Lapatinib	Phase 3 (in late-stage trials)
Larotaxel	Phase 3 (in late-stage trials)
Lasofoxifene	Phase 3 (in late-stage trials)
Lerociclib	Phase 3 (in late-stage trials)
Leuprolide	Phase 3 (in late-stage trials)
Lidocaine	Phase 3 (in late-stage trials)
Marimastat	Phase 3 (in late-stage trials)
Megestrol Acetate	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Metoprolol	Phase 3 (in late-stage trials)
Mifepristone	Phase 3 (in late-stage trials)
Mitomycin	Phase 3 (in late-stage trials)
Mometasone Furoate	Phase 3 (in late-stage trials)
Moxifloxacin	Phase 3 (in late-stage trials)
Neratinib	Phase 3 (in late-stage trials)
Niraparib	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Norethindrone Acetate	Phase 3 (in late-stage trials)
Odanacatib	Phase 3 (in late-stage trials)
Oxybutynin	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Pirarubicin	Phase 3 (in late-stage trials)
Poliglusam	Phase 3 (in late-stage trials)
Prasterone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Pregabalin	Phase 3 (in late-stage trials)
Progesterone	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Pyrotinib	Phase 3 (in late-stage trials)
Raloxifene	Phase 3 (in late-stage trials)
Ramucirumab	Phase 3 (in late-stage trials)
Ribociclib	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Ropivacaine	Phase 3 (in late-stage trials)
Sacituzumab Tirumotecan	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)
Saruparib	Phase 3 (in late-stage trials)
Serplulimab	Phase 3 (in late-stage trials)
Sesame Oil	Phase 3 (in late-stage trials)
Sintilimab	Phase 3 (in late-stage trials)
Sirolimus	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sorafenib	Phase 3 (in late-stage trials)
St. John’S Wort	Phase 3 (in late-stage trials)
Sulfur Hexafluoride	Phase 3 (in late-stage trials)
Sunitinib	Phase 3 (in late-stage trials)
Talazoparib	Phase 3 (in late-stage trials)
Tamoxifen	Phase 3 (in late-stage trials)
Taselisib	Phase 3 (in late-stage trials)
Tecemotide	Phase 3 (in late-stage trials)
Tegafur	Phase 3 (in late-stage trials)
Temsirolimus	Phase 3 (in late-stage trials)
Tesetaxel	Phase 3 (in late-stage trials)
Thiotepa	Phase 3 (in late-stage trials)
Tibolone	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)
Toremifene	Phase 3 (in late-stage trials)
Trastuzumab Duocarmazine	Phase 3 (in late-stage trials)
Trastuzumab Envedotin	Phase 3 (in late-stage trials)
Tretinoin	Phase 3 (in late-stage trials)
Triptorelin	Phase 3 (in late-stage trials)
Tucidinostat	Phase 3 (in late-stage trials)
Uracil	Phase 3 (in late-stage trials)
Veliparib	Phase 3 (in late-stage trials)
Vepdegestrant	Phase 3 (in late-stage trials)
Vinflunine	Phase 3 (in late-stage trials)
Vinorelbine	Phase 3 (in late-stage trials)
Vitamin E	Phase 3 (in late-stage trials)
Zanidatamab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Acetaminophen, Adebrelimab, Afimoxifene, Aflibercept, Alisertib, Amifostine, Amonafide, Amrubicin, Arsenic Trioxide, Arundine, Atropine, Azacitidine, Bavituximab, Bazedoxifene, Bendamustine, Benralizumab, Bexarotene, Binimetinib, Bintrafusp Alfa, Bisoprolol, Bortezomib, Bosutinib, Budesonide, Cabazitaxel, Cabozantinib, Cadonilimab, Calcitriol, Calcium Carbonate, Carvedilol, Catequentinib, Cediranib, Cemiplimab, Ceralasertib, Cetuximab, Chloroquine, Chondroitin Sulfate Sodium, Cimetidine, Clonidine, Cobimetinib, Colestipol Hydrochloride, Copanlisib, Copper, Crofelemer, Curcumin, Custirsen Sodium, Dactolisib, Dapagliflozin, Darolutamide, Dasatinib Anhydrous, Decitabine, Deferoxamine, Degarelix, Desmopressin, Digoxin, Diphenhydramine, Disulfiram, Doconexent, Dordaviprone, Dostarlimab, Dovitinib, Doxepin, Edotecarin, Encequidar, Endoxifen, Eniluracil, Enlonstobart, Envafolimab, Enzastaurin, Epalrestat, Epigalocatechin Gallate, Epinephrine, Eplerenone, Erlotinib, Estramustine, Famitinib, Famotidine, Fentanyl, Fianlimab, Figitumumab, Fludarabine, Fludarabine Phosphate, Fluoroestradiol, Fluoxymesterone, Flutemetamol, Folic Acid, Gabapentin, Gadobenate Dimeglumine, Ganetespib, Ganitumab, Gimeracil, Ginseng, American, Glucosamine, Glutamine, Glutathione, Gonadorelin, Honey, Hyaluronidase, Hyaluronidase (Human Recombinant), Hydralazine, Hydrogen Peroxide, Hydroxychloroquine, Hydroxytyrosol, INALIMAREV (CEA, MUC-1, VACCINIA VIRUS), Icosapent, Icotinib, Ifosfamide, Imatinib, Imetelstat Sodium, Imiquimod, Iodine, Ipilimumab, Irofulven, Ketamine, Ketoconazole, Lactobacillus Acidophilus, Lenvatinib, Lifileucel, Linifanib, Linsitinib, Liothyronine, Lisinopril Anhydrous, Lobaplatin, Lomustine, Lonafarnib, Loperamide, Loratadine, Losartan, Lovastatin, Lurbinectedin, Medroxyprogesterone Acetate, Metformin, Methylprednisolone, Midazolam, Milademetan, Monalizumab, Montmorillonite, Naltrexone, Naproxen, Neostigmine, Nimesulide, Nimotuzumab, Nintedanib, Nirogacestat, Nogapendekin Alfa, OMEGA-3-ACID ETHYL ESTERS, Ociperlimab, Omaveloxolone, Omeprazole, Onartuzumab, Ondansetron, Orteronel, Oteracil, Oxaliplatin, Oxiglutatione, Oxygen, PEGINTERFERON ALFA-2A, Paclitaxel Poliglumex, Palifosfamide, Palonosetron, Pamidronic Acid, Pamiparib, Panitumumab, Panobinostat, Pasireotide, Patritumab, Patritumab Deruxtecan, Patupilone, Pazopanib, Pelareorep, Pemetrexed, Pemigatinib, Penpulimab, Pentoxifylline, Perflutren, Perifosine, Perindopril, Pexidartinib, Pitavastatin, Platinum, Poziotinib, Pravastatin, Prednisolone, Propranolol, Racemetyrosine, Radium Dichloride, Rafutrombopag, Ranitidine, Recombinant Human Thrombopoietin, Regramostim, Reparixin, Retifanlimab, Retlirafusp Alfa, Rezvilutamide, Ridaforolimus, Rituximab, Romidepsin, Rosuvastatin, Rubitecan, Rucaparib, Ruxolitinib, Sabizabulin, Saracatinib, Satraplatin, Selinexor, Selumetinib, Sevoflurane, Simvastatin, Sitravatinib, Sodium Dichloroacetate, Sonidegib, Sulforaphane, Sulindac, Surufatinib, Tanespimycin, Tasisulam, Telapristone Acetate, Temozolomide, Teprotumumab, Thalidomide, Tiomolibdate Choline, Tipifarnib, Tipiracil, Tiragolumab, Tocilizumab, Tocotrienol, Topotecan, Toripalimab, Trabectedin, Tramadol, Trametinib, Trastuzumab Vedotin, Trebananib, Tremelimumab, Triamcinolone Acetonide, Triapine, Trifluridine, Trilaciclib, Ulipristal Acetate, Utomilumab, Valproic Acid, Valspodar, Vandetanib, Vatalanib, Venetoclax, Verteporfin, Vildagliptin, Vintafolide, Vismodegib, Vorinostat, Zafirlukast, Zenocutuzumab, Zibotentan, Zimberelimab, Zoledronic Acid Anhydrous, Zoptarelin Doxorubicin.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 11

Druggability breadth: 12 of 19 evidence-associated genes (63%) 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
BRCA1	RIBOFLAVIN
TP53	NITROFURANTOIN
CHEK2	NERATINIB
CFTR	IVACAFTOR
CKS1B	SELEXIPAG
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ATM	35	4
CHEK2	30	4
CFTR	14	4
BRCA1	12	4
JUN	3	3
IL2	2	2
CKS1B	1	4
BRCA2	0	0
DICER1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
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	ATM, TP53
FURAZOLIDONE	4	ATM, 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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
ATM	240	Binding:233, Functional:5, ADMET:2
JUN	88	Binding:87, Functional:1
IL2	35	Binding:34, ADMET:1
CKS1B	20	Binding:20
CDH1	18	Binding:18
BRCA1	13	Binding:9, Functional:4
DICER1	8	Binding:8
PTEN	8	Binding:8
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
DICER1	3.1.26.3	ribonuclease III
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase
GALNT12	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase
BRIP1	3.6.4.12	DNA helicase
GEN1	3.1.21.10	crossover junction endodeoxyribonuclease
ATM	2.7.11.1	non-specific serine/threonine protein kinase
BARD1	2.3.2.27	RING-type E3 ubiquitin transferase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

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
CFTR	520
ATM	240

Pharmacogenomics

Cohort genes with a PharmGKB record: 19; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

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)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
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	ATM, TP53
FURAZOLIDONE	4	ATM, 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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	BRCA1, TP53, CHEK2, CFTR, CKS1B, ATM
B	Phased (≥1) drug, not yet approved	2	IL2, JUN
C	Druggable family + PDB, no drug	6	DICER1, GALNT12, BRIP1, GEN1, IL7R, PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	BRCA2, CDH1, PALB2, PMS2, BARD1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
BRIP1	0	BRCA1
PALB2	0	BRCA1
PTEN	8	TP53
DICER1	8	—
CDH1	18	—
GALNT12	0	—
GEN1	0	—
IL7R	0	—
PMS2	1	—
BARD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,180.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	538
PHASE2	251
PHASE1	100
PHASE3	92
PHASE1/PHASE2	51
PHASE4	39
PHASE2/PHASE3	16
EARLY_PHASE1	13

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02004834	PHASE4	ACTIVE_NOT_RECRUITING	Levobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT05452213	PHASE4	RECRUITING	Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
NCT05465031	PHASE4	RECRUITING	Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
NCT07158164	PHASE4	RECRUITING	DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
NCT07162259	PHASE4	NOT_YET_RECRUITING	Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
NCT00092183	PHASE4	COMPLETED	An Investigational Drug for the Prevention of Chemotherapy-Induced Nausea and Vomiting (MK-0869-071)
NCT00128778	PHASE4	COMPLETED	Maintenance Treatment With Liposomal Doxorubicin (Caelyx) in Metastatic Breast Cancer Patients
NCT00302120	PHASE4	UNKNOWN	The MONET - Study: MR Mammography of Nonpalpable Breast Tumors
NCT00307606	PHASE4	UNKNOWN	Does a Single Steroid Injection Reduce the Formation of Postmastectomy Seroma
NCT00370240	PHASE4	COMPLETED	Chlorhydrate of Ropivacaine and Breast Cancer Surgery
NCT00375752	PHASE4	TERMINATED	Efficacy and Safety of Letrozole vs. Letrozole Plus Zoledronic Acid as Endocrine Therapy Before Surgery in Postmenopausal Patients With Breast Cancer
NCT00575354	PHASE4	COMPLETED	Comparison of Sevoflurane and Isoflurane Anesthesia for Benign Breast Tumor Excision
NCT00604968	PHASE4	TERMINATED	Pegylated Liposomal Doxorubicin (Caelyx(R)) as Monotherapy in Elderly Patients With Locally Advanced and/or Metastatic Breast Cancer (Study P05059)
NCT00616135	PHASE4	COMPLETED	Study of Autologous Fat Enhanced w/ Regenerative Cells Transplanted to Reconstruct Breast Deformities After Lumpectomy
NCT00649090	PHASE4	COMPLETED	A Study to Evaluate the Safety of Adjuvant Treatment With Exemestane Following Previous Treatment With Tamoxifen in Postmenopausal Women With Estrogen Sensitive Primary Breast Cancer
NCT00779285	PHASE4	TERMINATED	Safety Study of CAELYX in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines (Study P04057)(TERMINATED)
NCT01176916	PHASE4	COMPLETED	Aromasin® Interventional Study Of Early Invasive Breast Cancer Patients In China
NCT01427400	PHASE4	UNKNOWN	The Use of Botulinum Toxin A in Two-Stage Tissue Expander/ Implant Breast Reconstruction
NCT01849380	PHASE4	UNKNOWN	Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer
NCT01859936	PHASE4	COMPLETED	Will Preoperative MRI Breast in Women Under 56 Years With Breast Cancer Change Primary Treatment
NCT01948960	PHASE4	COMPLETED	Influence of Exceptional Patient Characteristics on Everolimus Exposure
NCT01961544	PHASE4	COMPLETED	Eribulin Mesylate Phase IV Clinical Trial in Korean Patients With Metastatic or Locally Advanced Breast Cancer
NCT01975064	PHASE4	COMPLETED	Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia
NCT02372305	PHASE4	WITHDRAWN	Comparison of FlexHD and Alloderm Outcomes in Breast Reconstructive Surgery
NCT02479347	PHASE4	COMPLETED	Wound Infections in Breast Cancer Surgery After Preoperative Skin Preparation With Chlorhexidine vs. Povidone-iodine
NCT02549677	PHASE4	COMPLETED	Epirubicin Versus Docetaxel Plus Cyclophosphamide in Lymph Node Negative, ER-positive, Her2-negative Breast Cancer
NCT02612870	PHASE4	UNKNOWN	Sienna+® Injection Time Study 4 Arms
NCT02627560	PHASE4	COMPLETED	The Effect of Topical Tranexamic Acid on Bleeding and Seroma Formation in After Undergoing Mastectomy
NCT02661932	PHASE4	COMPLETED	Fertility Preservation in Breast Cancer Patients
NCT02781259	PHASE4	UNKNOWN	Selective Lymph Node Dissection Using Fluorescent Dye in Node-positive Breast Cancer
NCT02819921	PHASE4	TERMINATED	Desvenlafaxine for Treatment of Hot Flashes in Women With Breast Cancer Taking Tamoxifen
NCT03220178	PHASE4	TERMINATED	Impact of eHealth-support on Quality of Life in Metastatic Breast Cancer Patients Treated With Palbociclib and Endocrine Therapy
NCT03583944	PHASE4	COMPLETED	A Study to Evaluate Safety, Tolerability and Efficacy of Eribulin Mesylate in Treating Adult Females With Locally Advanced or Metastatic Breast Cancer
NCT03586154	PHASE4	COMPLETED	Combined Intra-articular Shoulder Injection and Stellate Ganglion Block in Chronic Post-mastectomy Shoulder Pain
NCT04707196	PHASE4	COMPLETED	A Study of Abemaciclib in Indian Women With Advanced Breast Cancer
NCT04931615	PHASE4	COMPLETED	ARTISS a Single-centre Randomised Control Study
NCT05033769	PHASE4	UNKNOWN	Assessing ImmunoResponse Post Eribulin: Eribulin and Immunogenicity in Advanced Breast Cancer
NCT05036005	PHASE4	UNKNOWN	Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)
NCT05949333	PHASE4	UNKNOWN	Reducing Neutropenia Incidence With Pegfilgrastim Administration on Day 3 After Chemotherapy
NCT01357772	PHASE3	ACTIVE_NOT_RECRUITING	Trial of Low Dose Tamoxifen in Women With Breast Intraepithelial Neoplasia - Long Term Follow-up

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TAMOXIFEN	4	54
LETROZOLE	4	34
DOCETAXEL ANHYDROUS	4	18
SUNITINIB	4	18
EXEMESTANE	4	16
ERIBULIN	4	14
PALBOCICLIB	4	10
ABEMACICLIB	4	9
AFATINIB	4	7
FULVESTRANT	4	7
TRASTUZUMAB	4	7
ANASTROZOLE	4	6
DOXORUBICIN	4	6
LAPATINIB	4	6
NERATINIB	4	6
VINORELBINE	4	6
CAPECITABINE	4	5
PERTUZUMAB	4	5
TOREMIFENE	4	5
EPIRUBICIN	4	4
INDOCYANINE GREEN ACID FORM	4	4
TRASTUZUMAB DERUXTECAN	4	4
NIRAPARIB	4	3
OLAPARIB	4	3
TALAZOPARIB	4	3
TRASTUZUMAB EMTANSINE	4	3
CALCIUM CARBONATE	4	2
CETUXIMAB	4	2
EPOETIN ALFA	4	2
FLUOROURACIL	4	2

Cohort genes: BRCA1, BRCA2, TP53, CHEK2, DICER1, CDH1, BRIP1, PALB2, IL7R, JUN, ATM, PMS2, BARD1, PTEN, CFTR, CKS1B, GALNT12, GEN1, IL2
Drugs: Tamoxifen, Letrozole, Docetaxel, Sunitinib, Exemestane, Eribulin, Palbociclib, Abemaciclib, Afatinib, Fulvestrant, Trastuzumab, Anastrozole, Doxorubicin, Lapatinib, Neratinib, Vinorelbine, Capecitabine, Pertuzumab, Toremifene, Epirubicin, Indocyanine Green Acid Form, Trastuzumab Deruxtecan, Niraparib, Olaparib, Talazoparib, Trastuzumab Emtansine, Calcium Carbonate, Cetuximab, Epoetin Alfa, Fluorouracil