Breast cancer

Summary

Breast cancer (MONDO:0007254) is a cancer (an umbrella term covering 6 Mondo subtypes) caused by variants in BARD1 and TP53, with 79 cohort genes (626 GWAS associations across 77 studies; 70 CIViC-evidence somatic drivers; 2,007 ClinVar predisposition records) and 10,613 clinical trials. The dominant Reactome pathway is HDR through Homologous Recombination (HRR) (20 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Capecitabine + Lapatinib in Breast Cancer (CIViC Level A); 226 further subtype–drug associations are mapped below. Top therapeutic interventions include tamoxifen, docetaxel anhydrous, and epirubicin.

At a glance

• Classification: Cancer
• Causal genes: BARD1 (GenCC Definitive), TP53 (GenCC Definitive)
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 79
• GWAS associations: 626
• ClinVar variants: 2,007
• Clinical trials: 10,613
• Precision-medicine evidence (CIViC): 227 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	breast cancer
Mondo ID	MONDO:0007254
DOID	DOID:1612
ICD-10-CM	C50
ICD-11	1047754165
NCIT	C9335
SNOMED CT	254837009
UMLS	C0006142
MedGen	651
Anatomy (UBERON)	UBERON:0000310
Is cancer (heuristic)	yes

Also known as: breast cancer · breast tumor · breast tumour · cancer of breast · malignant breast neoplasm · malignant breast tumor · malignant breast tumour · malignant neoplasm of breast · malignant neoplasm of the breast · malignant tumor of breast · malignant tumor of the breast · malignant tumour of breast · malignant tumour of the breast · mammary tumor · mammary tumour · primary breast cancer

Data availability: 2,007 ClinVar variants · 626 GWAS associations (77 studies) · 21 GenCC gene-disease records.

Disease family

An umbrella term covering 6 Mondo subtypes.

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

Related subtypes (7): heart cancer, sternum cancer, mediastinal cancer, Askin tumor, pleural cancer, lung cancer, malignant neoplasm of chest wall

Subtypes (6): malignant breast phyllodes tumor, breast sarcoma, malignant breast melanoma, breast lymphoma, breast carcinoma, salivary gland type cancer of the breast

Genetics & variants

GWAS landscape

626 GWAS associations across 77 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1219648	4e-254	FGFR2	A
rs16886181	5e-122	C5orf67 - MAP3K1	T
rs3125719	4e-80	MTUS2	T	0.58
rs630965	1e-63	CHCHD4P2 - RPL36P14	C
rs2936870	5e-60	FGFR2	C	0.24
rs10995201	1e-56	LINC02929	A
rs4784227	5e-50	CASC16	T	0.25
rs2981575	8e-50	FGFR2	A	0.22
rs8051542	2e-47	TOX3	T
rs1421085	4e-47	FTO	T
rs6912323	3e-45	CCDC170 - ESR1	?
rs9383937	1e-44	CCDC170 - ESR1	?
rs3814113	2e-43	BNC2 - RN7SL720P	T
rs12922061	2e-33	CASC16	T	0.21
rs244353	1e-31	STXBP4	G
rs4729854	3e-30	RASA4DP - FAM185A	T
chr22:29551872	1e-29		?	1.41
rs910416	2e-29	ESR1	T
rs6826366	3e-28	ADAM29	G
rs9613774	8e-28	ZNRF3	G	0.7
rs7098100	4e-27	MLLT10	G
rs7650602	7e-27	ZBTB38	?
rs17474001	2e-26	STKLD1	T
rs8057044	2e-26	FTO	?
rs6785012	2e-26	ZBTB38	?
rs9411395	5e-26	LCN1P2	G
rs754537	5e-26	DNAJC27	?
rs10107982	6e-26	PCAT1, CASC8	?
rs7709971	1e-25	C5orf67 - MAP3K1	A	0.2
rs554219	3e-25	LINC01488 - PNCRNA-D	G	0.22

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90296487	Zhao X	2023	133,384	2,589,029	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90296488	Zhao X	2023	133,384	2,176,594	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90296489	Zhao X	2023	133,384	1,186,231	A large-scale genome-wide cross-trait analysis for the effect of COVID-19 on female-specific cancers.
GCST90270342	Guo H	2023	122,977	146,915	A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers.
GCST90270343	Guo H	2023	122,977	121,835	A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers.
GCST90429846	Jia G	2025	21,319	106,116	Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.
GCST90296719	Jia G	2024	18,034	22,104	Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction.
GCST90435600	Zhou W	2018	12,898	388,549	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90435601	Zhou W	2018	12,671	388,549	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90079108	Backman JD	2021	12,472	28,533	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	2
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	34
intergenic_variant	9
3_prime_UTR_variant	3
unknown	2
regulatory_region_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1219648	10	121586676	A>G,T	0.05	intron_variant	FGFR2	4e-254	Tier 4: intronic/intergenic
rs16886181	5	56733416	T>A,C,G	0.05	intergenic_variant	C5orf67 - MAP3K1	5e-122	Tier 4: intronic/intergenic
rs3125719	13	29416829	T>A,G	0.459	intron_variant	MTUS2	4e-80	Tier 4: intronic/intergenic
rs630965	9	108123199	C>A,G,T	0.05	intergenic_variant	CHCHD4P2 - RPL36P14	1e-63	Tier 4: intronic/intergenic
rs2936870	10	121589388	T>A,C	0.395	intron_variant	FGFR2	5e-60	Tier 4: intronic/intergenic
rs10995201	10	62540131	A>G	0.05	intron_variant	LINC02929	1e-56	Tier 4: intronic/intergenic
rs4784227	16	52565276	C>A,T	0.05	intron_variant	CASC16	5e-50	Tier 4: intronic/intergenic
rs2981575	10	121586602	G>A,C,T	0.05	intron_variant	FGFR2	8e-50	Tier 4: intronic/intergenic
rs8051542	16	52500255	T>C,G	0.05	intron_variant	TOX3	2e-47	Tier 4: intronic/intergenic
rs1421085	16	53767042	T>C	0.05	intron_variant	FTO	4e-47	Tier 4: intronic/intergenic
rs6912323	6	151637477	G>A,C,T	0.05	intergenic_variant	CCDC170 - ESR1	3e-45	Tier 4: intronic/intergenic
rs9383937	6	151635984	T>C	0.05	intergenic_variant	CCDC170 - ESR1	1e-44	Tier 4: intronic/intergenic
rs3814113	9	16915023	T>C	0.05	intergenic_variant	BNC2 - RN7SL720P	2e-43	Tier 4: intronic/intergenic
rs12922061	16	52601088	C>T	0.05	intron_variant	CASC16	2e-33	Tier 4: intronic/intergenic
rs244353	17	55117408	G>A	0.05	intron_variant	STXBP4	1e-31	Tier 4: intronic/intergenic
rs4729854	7	102743216	T>A	0.05	intron_variant	RASA4DP - FAM185A	3e-30	Tier 4: intronic/intergenic
chr22:29551872							1e-29	Tier 4: intronic/intergenic
rs910416	6	152111767	C>T	0.05	intergenic_variant	ESR1	2e-29	Tier 4: intronic/intergenic
rs6826366	4	174924959	G>A	0.05	intron_variant	ADAM29	3e-28	Tier 4: intronic/intergenic
rs9613774	22	29020763	T>G	0.361	intron_variant	ZNRF3	8e-28	Tier 4: intronic/intergenic
rs7098100	10	21545607	G>A	0.05	intron_variant	MLLT10	4e-27	Tier 4: intronic/intergenic
rs7650602	3	141428572	T>C	0.05	intron_variant	ZBTB38	7e-27	Tier 4: intronic/intergenic
rs17474001	9	133402020	C>A,T	0.05	intron_variant	STKLD1	2e-26	Tier 4: intronic/intergenic
rs8057044	16	53778702	G>A	0.05	intron_variant	FTO	2e-26	Tier 4: intronic/intergenic
rs6785012	3	141390506	C>A,G,T	0.05	intron_variant	ZBTB38	2e-26	Tier 4: intronic/intergenic
rs9411395	9	133317947	G>A	0.05	intron_variant	LCN1P2	5e-26	Tier 4: intronic/intergenic
rs754537	2	24953408	A>C,G,T	0.05	intron_variant	DNAJC27	5e-26	Tier 4: intronic/intergenic
rs10107982	8	127306510	T>C	0.05	intron_variant	PCAT1, CASC8	6e-26	Tier 4: intronic/intergenic
rs7709971	5	56711512	G>A,T	0.162	intron_variant	C5orf67 - MAP3K1	1e-25	Tier 4: intronic/intergenic
rs554219	11	69516874	C>A,G,T	0.12	intergenic_variant	LINC01488 - PNCRNA-D	3e-25	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

224 conflicting classifications of pathogenicity, 100 benign/likely benign, 74 pathogenic, 72 uncertain significance, 51 benign, 44 likely benign, 20 pathogenic/likely pathogenic, 14 likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
127547	NM_000136.3(FANCC):c.843+1G>A	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1049778	NM_000038.6(APC):c.-2_135+1824del	APC	Pathogenic	no assertion criteria provided
1049940	NM_000051.4(ATM):c.3403-1_3577-680del	ATM	Pathogenic	no assertion criteria provided
1076780	NM_000051.4(ATM):c.2840dup (p.Tyr947Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
1217268	NC_000011.9:g.(108225602_108235808)(108239827?)del	ATM	Pathogenic	criteria provided, single submitter
127334	NM_000051.4(ATM):c.1235G>A (p.Trp412Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
127340	NM_000051.4(ATM):c.1564_1565del (p.Glu522fs)	ATM	Pathogenic	reviewed by expert panel
127341	NM_000051.4(ATM):c.170G>A (p.Trp57Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
1343490	NC_000011.9:g.(108168110_108170440)_(108178712_108180886)del	ATM	Pathogenic	criteria provided, single submitter
140897	NM_000051.4(ATM):c.8565_8566delinsAA (p.Ser2855_Val2856delinsArgIle)	ATM	Pathogenic	reviewed by expert panel
141325	NM_000051.4(ATM):c.2284_2285del (p.Leu762fs)	ATM	Pathogenic	reviewed by expert panel
141416	NM_000051.4(ATM):c.5712dup (p.Ser1905fs)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
142057	NM_000051.4(ATM):c.2921+1G>T	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1049655	NM_000465.4(BARD1):c.1904-502_*2del	BARD1	Pathogenic	no assertion criteria provided
1050223	NM_000465.4(BARD1):c.1569-1_1677+2del	BARD1	Pathogenic	no assertion criteria provided
127725	NM_000465.4(BARD1):c.1935_1954dup (p.Glu652fs)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141702	NM_000465.4(BARD1):c.1921C>T (p.Arg641Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048829	NM_007294.4(BRCA1):c.5075-390_5193+2del	BRCA1	Pathogenic	no assertion criteria provided
1048853	NM_007294.4(BRCA1):c.302-167_441+3del	BRCA1	Pathogenic	no assertion criteria provided
1048961	NM_007294.4(BRCA1):c.4485-10_4491del	BRCA1	Pathogenic	no assertion criteria provided
1049017	NM_007294.4(BRCA1):c.5407-73_5467+4del	BRCA1	Pathogenic	no assertion criteria provided
1049103	NM_007294.4(BRCA1):c.5141_5144del (p.Val1714fs)	BRCA1	Pathogenic	no assertion criteria provided
1049208	NM_007294.4(BRCA1):c.672del (p.Ala225fs)	BRCA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1049236	NC_000017.11:g.43045676_43045803del	BRCA1	Pathogenic	no assertion criteria provided
1049239	NM_007294.4(BRCA1):c.1100del (p.Thr367fs)	BRCA1	Pathogenic	criteria provided, single submitter
1049275	NM_007294.4(BRCA1):c.5280del (p.Phe1761fs)	BRCA1	Pathogenic	no assertion criteria provided
1049277	NM_007294.4(BRCA1):c.3914dup (p.Asp1305fs)	BRCA1	Pathogenic	no assertion criteria provided
1049514	NM_007294.4(BRCA1):c.2827A>T (p.Lys943Ter)	BRCA1	Pathogenic	no assertion criteria provided
1049567	NM_007294.4(BRCA1):c.2_80+4del	BRCA1	Pathogenic	no assertion criteria provided
1049576	NM_007294.4(BRCA1):c.5194-1_5277+2del	BRCA1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 186 · Orphanet: 250 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
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
CHEK2	Act	BRCA	CIViC #8950
PALB2	LoF	OVT	CIViC #15013
FANCC			CIViC #1811
MLH1			CIViC #3532
MSH2			CIViC #3628
MSH6			CIViC #2478
NF2	LoF	CCRCC,CESC,HCC,HNSC,MEL,OVT,PAAD,PLMESO,PRCC,RCC	CIViC #3870
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
RAD51D			CIViC #4765
RET	Act	ANGS,MEL,NSCLC,PGNG,SOFT_TISSUE,WDTC	CIViC #42
ROS1	LoF	HCC,HNSC,OVT,PRAD,STAD	CIViC #4941
SF3B1	Act	AML,BLCA,BRCA,CHOL,CLLSLL,HCC,LUNG,MBL,MEL,PAAD,PCM,PRAD,SKCM,UM	CIViC #44
SGK1	Act	DLBCLNOS,MLYM,NHL,PRCC	CIViC #5225
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
AURKA			CIViC #61
TFF3			CIViC #5737
TIMP1			CIViC #5777
TLK2			CIViC #8787
TOP2A	Act	STAD	CIViC #5848
KMT2C	LoF	ACC,ACYC,AML,ANSC,BCC,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,ES,ESCA,GBC,HCC,HNSC,LUAD,LUSC,MBL,MEL,NPC,OVT,PAAD,PANCREAS,PANET,PAST,PGNG,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,STAD,STOMACH,UCEC,WDTC	CIViC #14089
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CCNE1			CIViC #11
CD274	LoF	DLBCLNOS	CIViC #11335
CDK6			CIViC #12
CDKN1B	LoF	BRCA,HCC,PCM,PRAD,SIC	CIViC #914

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
BARD1	Definitive	Autosomal dominant	breast cancer	4
TP53	Definitive	Autosomal dominant	breast cancer	12
ATRIP	Moderate	Autosomal dominant	breast cancer	3
LZTR1	Moderate	Autosomal dominant	breast cancer	15
MAP3K1	Moderate	Autosomal dominant	breast cancer	7
AURKA	Limited	Autosomal dominant	breast cancer	2
MSH6	Limited	Autosomal dominant	breast cancer	17
NTHL1	Limited	Autosomal recessive	breast cancer	7
PMS2	Limited	Autosomal dominant	breast cancer	15
RASAL1	Limited	Autosomal dominant	breast cancer
RECQL5	Limited	Autosomal dominant	breast cancer	2
ROS1	Limited	Autosomal dominant	breast cancer	2
BLM	Disputed Evidence	Autosomal dominant	breast cancer	12
FANCC	Disputed Evidence	Autosomal dominant	breast cancer	11
FANCM	Disputed Evidence	Autosomal dominant	breast cancer	10
MLH1	Disputed Evidence	Autosomal dominant	breast cancer	19
MRE11	Disputed Evidence	Autosomal dominant	breast cancer	8
MSH2	Disputed Evidence	Autosomal dominant	breast cancer	17
RECQL	Disputed Evidence	Autosomal dominant	breast cancer	4
RINT1	Disputed Evidence	Autosomal dominant	breast cancer	8
XRCC2	Disputed Evidence	Autosomal dominant	breast cancer	10

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
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
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
PALB2	Orphanet:1333	Familial pancreatic carcinoma
PALB2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PALB2	Orphanet:178	Chordoma
PALB2	Orphanet:227535	Hereditary breast cancer

Cohort genes → proteins

79 cohort genes, 79 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	50
multi_evidence	29

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gencc,clinvar,civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar,civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar,civic_evidence
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar,civic_evidence
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar,civic_evidence
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	gencc,clinvar
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	gencc,clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	gencc,clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	gencc,clinvar
NF2	HGNC:7773	ENSG00000186575	P35240	Merlin	clinvar,civic_evidence
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	gencc,clinvar
BARD1	HGNC:952	ENSG00000138376	Q99728	BRCA1-associated RING domain protein 1	gencc,clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar,civic_evidence
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	clinvar,civic_evidence
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	clinvar,civic_evidence
ROS1	HGNC:10261	ENSG00000047936	P08922	Proto-oncogene tyrosine-protein kinase ROS	gencc
BLM	HGNC:1058	ENSG00000197299	P54132	RecQ-like DNA helicase BLM	gencc
SF3B1	HGNC:10768	ENSG00000115524	O75533	Splicing factor 3B subunit 1	civic_evidence
SGK1	HGNC:10810	ENSG00000118515	O00141	Serine/threonine-protein kinase Sgk1	civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
AURKA	HGNC:11393	ENSG00000087586	O14965	Aurora kinase A	gencc
TFF3	HGNC:11757	ENSG00000160180	Q07654	Trefoil factor 3	civic_evidence
TIMP1	HGNC:11820	ENSG00000102265	P01033	Metalloproteinase inhibitor 1	civic_evidence
TLK2	HGNC:11842	ENSG00000146872	Q86UE8	Serine/threonine-protein kinase tousled-like 2	civic_evidence
TOP2A	HGNC:11989	ENSG00000131747	P11388	DNA topoisomerase 2-alpha	civic_evidence
XRCC2	HGNC:12829	ENSG00000196584	O43543	DNA repair protein XRCC2	gencc
KMT2C	HGNC:13726	ENSG00000055609	Q8NEZ4	Histone-lysine N-methyltransferase 2C	civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
CCNE1	HGNC:1589	ENSG00000105173	P24864	G1/S-specific cyclin-E1	civic_evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
CDK6	HGNC:1777	ENSG00000105810	Q00534	Cyclin-dependent kinase 6	civic_evidence
CDKN1B	HGNC:1785	ENSG00000111276	P46527	Cyclin-dependent kinase inhibitor 1B	civic_evidence
RSF1	HGNC:18118	ENSG00000048649	Q96T23	Remodeling and spacing factor 1	civic_evidence
TUBB3	HGNC:20772	ENSG00000258947	Q13509	Tubulin beta-3 chain	civic_evidence
RINT1	HGNC:21876	ENSG00000135249	Q6NUQ1	RAD50-interacting protein 1	gencc
FANCM	HGNC:23168	ENSG00000187790	Q8IYD8	Fanconi anemia group M protein	gencc
CYP2D6	HGNC:2625	ENSG00000100197	P10635	Cytochrome P450 2D6	civic_evidence
PARP1	HGNC:270	ENSG00000143799	P09874	Poly [ADP-ribose] polymerase 1	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
AGR2	HGNC:328	ENSG00000106541	O95994	Anterior gradient protein 2 homolog	civic_evidence
ATRIP	HGNC:33499	ENSG00000164053	Q8WXE1	ATR-interacting protein	gencc
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
ERBB3	HGNC:3431	ENSG00000065361	P21860	Receptor tyrosine-protein kinase erbB-3	civic_evidence
ERBB4	HGNC:3432	ENSG00000178568	Q15303	Receptor tyrosine-protein kinase erbB-4	civic_evidence
ESR1	HGNC:3467	ENSG00000091831	P03372	Estrogen receptor	civic_evidence
FCGR2A	HGNC:3616	ENSG00000143226	P12318	Low affinity immunoglobulin gamma Fc region receptor II-a	civic_evidence
FCGR2B	HGNC:3618	ENSG00000072694	P31994	Low affinity immunoglobulin gamma Fc region receptor II-b	civic_evidence
FCGR3A	HGNC:3619	ENSG00000203747	P08637	Low affinity immunoglobulin gamma Fc region receptor III-A	civic_evidence
FDXR	HGNC:3642	ENSG00000161513	P22570	NADPH:adrenodoxin oxidoreductase, mitochondrial	civic_evidence
FGF3	HGNC:3681	ENSG00000186895	P11487	Fibroblast growth factor 3	civic_evidence

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.
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.
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.
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.
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
NF2	Merlin	Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis.
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.
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.
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…
ROS1	Proto-oncogene tyrosine-protein kinase ROS	Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium.
BLM	RecQ-like DNA helicase BLM	ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3’-5’ direction.
SF3B1	Splicing factor 3B subunit 1	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
SGK1	Serine/threonine-protein kinase Sgk1	Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration a…
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
AURKA	Aurora kinase A	Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression.
TFF3	Trefoil factor 3	Involved in the maintenance and repair of the intestinal mucosa.
TIMP1	Metalloproteinase inhibitor 1	Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor.
TLK2	Serine/threonine-protein kinase tousled-like 2	Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation.
TOP2A	DNA topoisomerase 2-alpha	Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken stra…
XRCC2	DNA repair protein XRCC2	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions.
KMT2C	Histone-lysine N-methyltransferase 2C	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
CCNE1	G1/S-specific cyclin-E1	Essential for the control of the cell cycle at the G1/S (start) transition.
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
CDK6	Cyclin-dependent kinase 6	Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.
CDKN1B	Cyclin-dependent kinase inhibitor 1B	Important regulator of cell cycle progression.
RSF1	Remodeling and spacing factor 1	Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcripti…
TUBB3	Tubulin beta-3 chain	Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers.
RINT1	RAD50-interacting protein 1	Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER.
FANCM	Fanconi anemia group M protein	DNA-dependent ATPase component of the Fanconi anemia (FA) core complex.
CYP2D6	Cytochrome P450 2D6	A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids.
PARP1	Poly [ADP-ribose] polymerase 1	Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
AGR2	Anterior gradient protein 2 homolog	Required for MUC2 post-transcriptional synthesis and secretion.
ATRIP	ATR-interacting protein	Required for checkpoint signaling after DNA damage.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
ERBB3	Receptor tyrosine-protein kinase erbB-3	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
ERBB4	Receptor tyrosine-protein kinase erbB-4	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell prolife…
ESR1	Estrogen receptor	Nuclear hormone receptor.
FCGR2A	Low affinity immunoglobulin gamma Fc region receptor II-a	Binds to the Fc region of immunoglobulins gamma.
FCGR2B	Low affinity immunoglobulin gamma Fc region receptor II-b	Receptor for the Fc region of complexed or aggregated immunoglobulins gamma.
FCGR3A	Low affinity immunoglobulin gamma Fc region receptor III-A	Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG).
FDXR	NADPH:adrenodoxin oxidoreductase, mitochondrial	Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylat…
FGF3	Fibroblast growth factor 3	Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.

Protein-family classification

Druggable: 41 · Difficult: 10 · Unknown: 28 · Druggable fraction: 0.52

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	23	8.1×	3e-14
Nuclear receptor	2	9.8×	0.080
Antibody/Immunoglobulin	5	1.9×	0.403
Transporter	2	2.0×	0.607
Enzyme (other)	8	1.2×	0.607
Phosphatase	1	1.1×	0.809
Transcription factor	9	0.9×	0.809
Other/Unknown	28	0.6×	1.000
Scaffold/PPI	1	0.2×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
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
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
FANCC	Other/Unknown	no		FANCC
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
NF2	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_sf
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
RAD51D	Other/Unknown	no		AAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom
ROS1	Kinase	yes	2.7.10.1	LDLR_classB_rpt, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
BLM	Enzyme (other)	yes	3.6.4.12	Helicase_C-like, HRDC_dom, DNA/RNA_helicase_DEAH_CS
SF3B1	Other/Unknown	no		ARM-like, SF3b_su1, ARM-type_fold
SGK1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
AURKA	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TFF3	Other/Unknown	no		P_trefoil_dom, P_trefoil_CS, P_trefoil_chordata
TIMP1	Enzyme (other)	yes	3.4.24.22	Netrin_domain, TIMP, TIMP-like_OB-fold
TLK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TOP2A	Enzyme (other)	yes	5.6.2.2	TopoII_euk, Topo_IIA, Topo_IIA_dom_A
XRCC2	Other/Unknown	no		Rad51_C, RecA_ATP-bd, P-loop_NTPase
KMT2C	Transcription factor	no		HMGI/Y_DNA-bd_CS, SET_dom, Znf_RING
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CCNE1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
CDK6	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CDKN1B	Other/Unknown	no		CDI_dom, CDI_dom_sf
RSF1	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
TUBB3	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
RINT1	Other/Unknown	no		RINT1_Tip20, EXOC6PINT-1/Sec15/Tip20_C_dom2
FANCM	Other/Unknown	no		Helicase_C-like, ERCC4_domain, RuvA_2-like
CYP2D6	Enzyme (other)	yes	1.14.14.1	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_E_grp-I_CYP2D-like
PARP1	Transcription factor	no	2.4.2.30	BRCT_dom, Znf_PARP, Poly(ADP-ribose)pol_reg_dom
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
AGR2	Other/Unknown	no		Thioredoxin-like_sf, AGR/TXD
ATRIP	Other/Unknown	no		ATRIP
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB3	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB4	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ESR1	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt
FCGR2A	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
FCGR2B	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
FCGR3A	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig-like_fold
FDXR	Other/Unknown	no		Ferredox_Rdtase_adrenod, FAD/NAD-bd_sf, Ferredox_Rdtase
FGF3	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF

Expression context

Cohort genes with no expression data: 0.

73 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)	79
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	12
secondary oocyte	11
calcaneal tendon	11
oocyte	10
ganglionic eminence	8
male germ line stem cell (sensu Vertebrata) in testis	8
buccal mucosa cell	7
primordial germ cell in gonad	5
adrenal tissue	5
lower esophagus mucosa	4
embryo	4
endometrium epithelium	4
stromal cell of endometrium	4
tendon of biceps brachii	3
pancreatic ductal cell	3
right lobe of liver	3
sperm	3
corpus epididymis	3
tibia	3
colonic epithelium	3

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
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
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
FANCC	195	ubiquitous	marker	pancreatic ductal cell, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
NF2	283	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, dorsal motor nucleus of vagus nerve
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
RAD51D	187	ubiquitous	yes	sperm, male germ cell, oocyte
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta
ROS1	79	tissue_specific	marker	upper lobe of left lung, upper lobe of lung, corpus epididymis
BLM	199	ubiquitous	marker	parotid gland, primordial germ cell in gonad, secondary oocyte
SF3B1	295	ubiquitous	marker	tibia, ventricular zone, epithelium of nasopharynx
SGK1	299	ubiquitous	marker	palpebral conjunctiva, eye, right lung
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
AURKA	236	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
TFF3	199	broad	marker	mucosa of transverse colon, ileal mucosa, left lobe of thyroid gland
TIMP1	296	ubiquitous	marker	right coronary artery, left coronary artery, gall bladder
TLK2	185	tissue_specific	marker	calcaneal tendon, sural nerve, colonic epithelium
TOP2A	217	ubiquitous	marker	ventricular zone, ganglionic eminence, secondary oocyte
XRCC2	283	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral globus pallidus
KMT2C	261	ubiquitous	marker	oocyte, caput epididymis, upper arm skin
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CCNE1	201	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung

Protein interactions among cohort

Intra-cohort edges: 203.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
AKT1	16,601
KRAS	14,509
ESR1	12,382
PTEN	11,626
ERBB2	9,659
MTOR	9,490
BRCA1	9,064
PARP1	8,370

Intra-cohort edges

A	B	Sources
ABCB1	CYP2D6	string_interaction
ABCC3	EGFR	intact
ABCC3	MLH1	intact
AGR2	ERBB3	string_interaction
AGR2	ESR1	string_interaction
AGR2	TFF3	string_interaction
AKT1	AKT2	intact
AKT1	AKT3	biogrid_interaction, intact
AKT1	CCND1	string_interaction
AKT1	FANCC	intact
AKT1	FGF3	intact
AKT1	MTOR	intact, string_interaction
AKT1	PIK3CA	biogrid_interaction, string_interaction
AKT1	PIK3R1	string_interaction
AKT1	PTEN	string_interaction
AKT1	ROS1	intact
AKT2	AKT3	intact
AKT2	PIK3CA	string_interaction
AKT2	PIK3R1	string_interaction
AKT2	PTEN	string_interaction
AKT3	BRAF	intact
AKT3	PIK3CA	string_interaction
AKT3	PIK3R1	string_interaction
AKT3	PTEN	string_interaction
ATRIP	CHEK2	string_interaction
AURKA	BRCA1	string_interaction
AURKA	EGFR	intact
AURKA	MKI67	string_interaction
AURKA	TP53	string_interaction
BARD1	BRCA1	biogrid_interaction, intact, string_interaction
BARD1	BRCA2	string_interaction
BARD1	CHEK2	string_interaction
BARD1	PALB2	string_interaction
BARD1	RAD51D	string_interaction
BARD1	XRCC2	string_interaction
BLM	FANCC	string_interaction
BLM	FANCM	string_interaction
BLM	MLH1	string_interaction
BLM	MSH6	string_interaction
BLM	XRCC2	biogrid_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	EGFR	biogrid_interaction
BRAF	FGFR2	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MAP3K1	intact
BRAF	MLH1	string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	PMS2	string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	ROS1	intact

Structural data

PDB: 73 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
ESR1	P03372	478
EGFR	P00533	388
TP53	P04637	313
AURKA	O14965	193
PIK3CA	P42336	135
BRAF	P15056	131
PARP1	P09874	106
PIK3R1	P27986	105
FGFR1	P11362	83
CD274	Q9NZQ7	76
SF3B1	O75533	74
MTOR	P42345	70
ERBB2	P04626	63
FGFR2	P21802	63
IGF1R	P08069	46
AKT1	P31749	43
CHEK2	O96017	38
RET	P07949	34
BRCA1	P38398	33
MSH2	P43246	30
RECQL5	O94762	29
TUBB3	Q13509	28
ABCB1	P08183	24
ERBB3	P21860	23
CCNE1	P24864	22
CDK6	Q00534	22
PGR	P06401	20
CDKN1B	P46527	19
AKT2	P31751	19

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FDXR	P22570	91.66
RASAL1	O95294	88.64
RINT1	Q6NUQ1	85.97
FGF3	P11487	79.32
KLLN	B2CW77	51.20
RSF1	Q96T23	48.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 855. Enrichment computed across 129 evidence-associated genes (117 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 117 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)	20	32.5×	8e-23	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+12 more)
Homologous DNA Pairing and Strand Exchange	16	52.1×	3e-22	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+8 more)
Impaired BRCA2 binding to PALB2	14	54.7×	7e-20	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+6 more)
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	14	50.6×	2e-19	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+6 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	14	50.6×	2e-19	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+6 more)
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	14	50.6×	2e-19	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+6 more)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	14	47.1×	5e-19	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+6 more)
Resolution of D-loop Structures through Holliday Junction Intermediates	15	38.5×	8e-19	BRCA1, BRCA2, PALB2, BARD1, RAD51D, BLM, WRN, XRCC2 (+7 more)
Presynaptic phase of homologous DNA pairing and strand exchange	15	34.9×	4e-18	BRCA1, BRCA2, BARD1, RAD51D, BLM, WRN, XRCC2, BRIP1 (+7 more)
Diseases of DNA repair	12	58.6×	8e-18	BRCA1, BRCA2, MLH1, MSH2, MSH6, BARD1, BLM, ATRIP (+4 more)
Cell Cycle	25	7.7×	8e-14	BRCA1, BRCA2, MLH1, BARD1, BLM, AURKA, TERT, CCND1 (+17 more)
Impaired BRCA2 binding to RAD51	12	31.7×	8e-14	BRCA1, BRCA2, BARD1, BLM, WRN, BRIP1, ATRIP, MRE11 (+4 more)
Diseases of DNA Double-Strand Break Repair	9	62.8×	1e-13	BRCA1, BRCA2, BARD1, BLM, ATRIP, MRE11, NBN, ATM (+1 more)
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	9	62.8×	1e-13	BRCA1, BRCA2, BARD1, BLM, ATRIP, MRE11, NBN, ATM (+1 more)
Regulation of TP53 Activity	15	17.0×	4e-13	BRCA1, BARD1, BLM, SGK1, STK11, AURKA, ATRIP, AKT1 (+7 more)
PIP3 activates AKT signaling	19	10.8×	4e-13	SGK1, CDKN1B, EGFR, ERBB2, ERBB3, ERBB4, ESR1, FGF3 (+11 more)
Transcriptional Regulation by TP53	19	10.1×	1e-12	BRCA1, MLH1, MSH2, BARD1, BLM, SGK1, STK11, AURKA (+11 more)
Regulation of TP53 Activity through Phosphorylation	15	15.1×	2e-12	TP53, BRCA1, CHEK2, BARD1, BLM, STK11, AURKA, WRN (+7 more)
Homology Directed Repair	11	29.0×	2e-12	BRCA1, BRCA2, BARD1, BLM, SLX4, ABRAXAS1, ATRIP, MRE11 (+3 more)
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	11	29.0×	2e-12	BRCA1, BRCA2, BARD1, BLM, SLX4, ABRAXAS1, ATRIP, MRE11 (+3 more)
HDR through Single Strand Annealing (SSA)	11	27.5×	4e-12	BRCA1, BARD1, BLM, WRN, BRIP1, ATRIP, MRE11, NBN (+3 more)
Fanconi Anemia Pathway	11	26.2×	8e-12	FANCC, FANCM, SLX4, FANCI, ATRIP, FANCA, FANCB, FANCD2 (+3 more)
G2/M DNA damage checkpoint	14	14.4×	2e-11	TP53, BRCA1, CHEK2, BARD1, BLM, WRN, BRIP1, ABRAXAS1 (+6 more)
DNA Double-Strand Break Repair	11	23.3×	3e-11	BRCA1, BRCA2, BARD1, BLM, SLX4, ABRAXAS1, ATRIP, MRE11 (+3 more)
Resolution of D-Loop Structures	8	43.4×	1e-10	BRCA1, BRCA2, BARD1, BLM, SLX4, MRE11, NBN, ATM
Defective homologous recombination repair (HRR) due to PALB2 loss of function	7	56.9×	2e-10	BRCA1, BRCA2, BARD1, BLM, MRE11, NBN, ATM
DNA Repair	14	11.8×	3e-10	BRCA1, BRCA2, MLH1, MSH2, MSH6, BARD1, BLM, SLX4 (+6 more)
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	14	11.6×	4e-10	EGFR, ERBB2, ERBB3, ERBB4, ESR1, FGF3, FGFR1, FGFR2 (+6 more)
TP53 Regulates Transcription of DNA Repair Genes	11	17.0×	9e-10	TP53, BRCA1, FANCC, MLH1, MSH2, PMS2, RAD51D, FANCI (+3 more)
RNA Polymerase II Transcription	25	4.8×	1e-09	BRCA1, MLH1, MSH2, BARD1, BLM, SGK1, SMARCA4, STK11 (+17 more)

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 128 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA repair	25	12.5×	2e-17	BRCA1, FANCC, MSH2, MSH6, BARD1, RAD51D, BLM, XRCC2 (+17 more)
double-strand break repair	15	23.8×	5e-14	TP53, BRCA1, BRCA2, CHEK2, MSH2, WRN, BRIP1, ABRAXAS1 (+7 more)
double-strand break repair via homologous recombination	16	19.5×	8e-14	BRCA1, BRCA2, PALB2, RAD51D, BLM, WRN, XRCC2, SLX4 (+8 more)
telomere maintenance	13	27.2×	5e-13	RAD51D, BLM, TERT, WRN, CCNE1, PARP1, MRE11, NBN (+5 more)
DNA damage response	22	9.2×	8e-13	TP53, BRCA1, CHEK2, BARD1, BLM, SGK1, STK11, TLK2 (+14 more)
interstrand cross-link repair	10	33.8×	7e-11	FANCC, RAD51D, FANCM, FANCI, FANCA, FANCB, FANCD2, FANCE (+2 more)
mitotic G2/M transition checkpoint	7	43.9×	3e-08	BRCA1, BARD1, ABRAXAS1, MRE11, NBN, ATR, RAD50
homologous recombination	6	65.8×	3e-08	BRCA1, BARD1, BRIP1, MRE11, NBN, RAD50
mismatch repair	7	35.5×	1e-07	MLH1, MSH2, MSH6, PMS2, WRN, MLH3, MUTYH
DNA strand resection involved in replication fork processing	5	82.3×	2e-07	BRCA1, BARD1, MRE11, NBN, RAD50
replicative senescence	6	46.5×	3e-07	TP53, CHEK2, TERT, WRN, ATM, ATR
response to X-ray	6	41.6×	6e-07	TP53, BRCA2, MSH2, BLM, XRCC2, CCND1
DNA replication	10	12.9×	7e-07	BLM, WRN, SLX4, ATR, POLD1, POLE, POLH, RECQL (+2 more)
protein phosphorylation	14	7.4×	7e-07	CHEK2, ROS1, SGK1, BRAF, STK11, AURKA, TLK2, CCNE1 (+6 more)
telomere maintenance via recombination	5	59.8×	1e-06	BRCA2, RAD51D, TERT, RAD50, RAD51C
DNA double-strand break processing	5	59.8×	1e-06	BLM, MRE11, NBN, ATM, RAD50
phosphatidylinositol 3-kinase/protein kinase B signal transduction	9	14.8×	1e-06	PTEN, EGFR, ERBB2, ERBB3, FCGR3A, AKT1, IGF1R, PIK3CA (+1 more)
mitotic G2 DNA damage checkpoint signaling	7	24.2×	1e-06	BRCA1, BLM, RINT1, ABRAXAS1, MRE11, NBN, ATM
regulation of cell cycle	13	7.6×	2e-06	TP53, BRCA1, NF2, BARD1, RAD51D, STK11, TSC1, CDK6 (+5 more)
negative regulation of apoptotic process	18	4.9×	2e-06	TP53, PALB2, BARD1, BRAF, AURKA, TIMP1, EGFR, ERBB2 (+10 more)
regulation of signal transduction by p53 class mediator	7	20.9×	3e-06	CHEK2, SGK1, STK11, AURKA, AKT1, MTOR, ATM
somitogenesis	7	20.5×	3e-06	TP53, PALB2, BMPR1A, XRCC2, ATM, AXIN2, PRKDC
cellular response to gamma radiation	6	28.2×	4e-06	TP53, CHEK2, TLK2, WRN, ATM, ATR
response to gamma radiation	6	27.2×	5e-06	TP53, BRCA2, XRCC2, PARP1, FANCD2, PRKDC
reciprocal meiotic recombination	6	26.3×	6e-06	RAD51D, MLH3, MRE11, ATM, RAD50, RAD51C
intrinsic apoptotic signaling pathway in response to DNA damage	7	17.7×	8e-06	BRCA1, CHEK2, MLH1, MSH6, ATM, PIK3R1, PRKDC
protein autophosphorylation	9	10.2×	2e-05	CHEK2, STK11, AURKA, ERBB4, FGFR1, FGFR2, AKT1, IGF1R (+1 more)
telomeric D-loop disassembly	4	58.5×	2e-05	BLM, WRN, SLX4, RECQL4
DNA damage checkpoint signaling	6	18.4×	5e-05	CHEK2, BRIP1, ATRIP, NBN, ATM, ATR
epidermal growth factor receptor signaling pathway	7	13.6×	5e-05	BRAF, EGFR, ERBB2, ERBB3, ERBB4, AKT1, PIK3CA

Therapeutics

Drug target analysis

Approved (phase 4): 39 · Phase ≥3: 40 · Phased (≥1): 45 · Undrugged: 34

Druggability breadth: 91 of 129 evidence-associated genes (71%) 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
BRCA1	RIBOFLAVIN
CHEK2	NERATINIB
RET	PONATINIB
ROS1	LORLATINIB
BLM	AMIFOSTINE
BRAF	VEMURAFENIB
AURKA	INAMRINONE
TLK2	FEDRATINIB
TOP2A	IDARUBICIN
CCND1	PALBOCICLIB
CCNE1	PALBOCICLIB
CD274	MOCLOBEMIDE
CDK6	PALBOCICLIB
TUBB3	COLCHICINE
CYP2D6	LEVOSALBUTAMOL
PARP1	NIRAPARIB
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
ERBB3	MOBOCERTINIB
ERBB4	MOBOCERTINIB
ESR1	CANDESARTAN CILEXETIL
FGFR1	PONATINIB
FGFR2	PONATINIB
FGFR3	PONATINIB
AKT1	CAPIVASERTIB
AKT2	CAPIVASERTIB
AKT3	CAPIVASERTIB
MTOR	SALMETEROL XINAFOATE
ABCB1	PROGESTERONE
ABCC3	TELMISARTAN
IGF1R	FEDRATINIB
KRAS	VEMURAFENIB
MAP3K1	PONATINIB
NCOA3	METHOTREXATE
PGR	CANDESARTAN CILEXETIL
PIK3CA	IDELALISIB
PIK3R1	IDELALISIB
RECQL	LEVODOPA

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP2D6	436	4
BLM	284	4
PGR	264	4
TP53	196	4
EGFR	175	4
MTOR	164	4
ESR1	162	4
RET	135	4
ABCB1	119	4
RECQL	115	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	ESR1, PGR, RECQL, TP53
DIENESTROL	4	CYP2D6, ESR1, TP53
CLOTRIMAZOLE	4	ABCB1, BLM, CYP2D6, EGFR, ERBB2, TP53
COLCHICINE	4	CYP2D6, TP53, TUBB3
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	BLM, MTOR, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	CYP2D6, MTOR, TP53
RALOXIFENE HYDROCHLORIDE	4	BLM, ESR1, TP53
NICARDIPINE HYDROCHLORIDE	4	BLM, CYP2D6, TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	PGR, 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	RECQL, TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	BLM, TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	BLM, RECQL, TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 36.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
CYP2D6	3,659	ADMET:3565, Binding:91, Functional:2, Toxicity:1
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
ESR1	2,435	Binding:2037, Functional:363, ADMET:35
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
AKT1	1,942	Binding:1900, Functional:34, ADMET:7, Toxicity:1
TUBB3	1,781	Binding:1741, Functional:34, ADMET:6
RET	1,586	Binding:1573, Functional:10, ADMET:3
AURKA	1,500	Binding:1483, Functional:10, ADMET:7
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
MTOR	1,375	Binding:1335, Functional:37, ADMET:2, Toxicity:1
TOP2A	1,305	Binding:1264, ADMET:22, Functional:13, Toxicity:6
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
IGF1R	1,091	Binding:1037, Functional:53, ADMET:1
FGFR3	975	Binding:948, Functional:18, ADMET:9
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
PARP1	825	Binding:814, Functional:8, ADMET:3
AKT2	822	Binding:802, Functional:19, Toxicity:1
CDK6	715	Binding:691, Functional:24
CCNE1	691	Binding:690, ADMET:1
CHEK2	690	Binding:687, Functional:2, ADMET:1
AKT3	660	Binding:644, Functional:16
PGR	643	Binding:401, Functional:231, ADMET:11
ERBB4	591	Binding:579, ADMET:8, Functional:4
CCND1	576	Binding:574, Functional:1, ADMET:1
SGK1	538	Binding:535, ADMET:2, Functional:1
CD274	525	Binding:520, Functional:5
PIK3R1	493	Binding:470, ADMET:23
ROS1	461	Binding:459, Functional:2
TLK2	185	Binding:185
ERBB3	169	Binding:169
MAP3K1	167	Binding:165, ADMET:1, Functional:1
BLM	82	Binding:78, Functional:4
RB1	59	Binding:59
NCOA3	42	Binding:39, Functional:3
ABCC3	37	Binding:21, ADMET:16
MRE11	36	Binding:36
ATRIP	31	Binding:31
KMT2C	29	Binding:29
MYD88	26	Binding:26
MTAP	24	Binding:23, ADMET:1
SF3B1	22	Binding:22
BRCA1	13	Binding:9, Functional:4
MSH6	10	Binding:10
MSH2	9	Binding:9
PTEN	8	Binding:8
NTHL1	8	Binding:7, Functional: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
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
RET	2.7.10.1	receptor protein-tyrosine kinase
ROS1	2.7.10.1	receptor protein-tyrosine kinase
BLM	3.6.4.12	DNA helicase
SGK1	2.7.11.1	non-specific serine/threonine protein kinase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
AURKA	2.7.11.1	non-specific serine/threonine protein kinase
TIMP1	3.4.24.22	stromelysin 2
TOP2A	5.6.2.2, 5.99.1.3	DNA topoisomerase (ATP-hydrolysing), DNA topoisomerase (ATP-hydrolysing)
CDK6	2.7.11.22	cyclin-dependent kinase
CYP2D6	1.14.14.1, 1.14.99.38	unspecific monooxygenase, cholesterol 25-monooxygenase
PARP1	2.4.2.30	NAD+ ADP-ribosyltransferase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
ERBB3	2.7.10.1	receptor protein-tyrosine kinase
ERBB4	2.7.10.1	receptor protein-tyrosine kinase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
AKT1	2.7.11.1	non-specific serine/threonine protein kinase
AKT2	2.7.11.1	non-specific serine/threonine protein kinase
AKT3	2.7.11.1	non-specific serine/threonine protein kinase
ABCB1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
ABCC3	7.6.2.3	ABC-type glutathione-S-conjugate transporter
IGF1R	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
MAP3K1	2.7.11.25	mitogen-activated protein kinase kinase kinase
MTAP	2.4.2.28	S-methyl-5’-thioadenosine phosphorylase
NCOA3	2.3.1.48	histone acetyltransferase
NTHL1	4.2.99.18	DNA-(apurinic or apyrimidinic site) lyase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PIK3R1	2.7.1.153	phosphatidylinositol-4,5-bisphosphate 3-kinase
RECQL	3.6.4.12	DNA helicase

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
RET	1,586
ROS1	461
SGK1	538
BRAF	1,442
AURKA	1,500
TLK2	185
TOP2A	1,305
CCND1	576
CCNE1	691
CD274	525
CDK6	715
TUBB3	1,781
CYP2D6	3,659
PARP1	825
EGFR	6,531
ERBB2	1,221
ERBB3	169
ERBB4	591
ESR1	2,435
FGFR1	1,465
FGFR2	966
FGFR3	975
AKT1	1,942
AKT2	822
AKT3	660
MTOR	1,375
ABCB1	3,063
IGF1R	1,091

Pharmacogenomics

Cohort genes with a PharmGKB record: 79; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CYP2D6	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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	ESR1, PGR, RECQL, TP53
DIENESTROL	4	CYP2D6, ESR1, TP53
CLOTRIMAZOLE	4	ABCB1, BLM, CYP2D6, EGFR, ERBB2, TP53
COLCHICINE	4	CYP2D6, TP53, TUBB3
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	BLM, MTOR, TP53
AMIODARONE HYDROCHLORIDE	4	BLM, TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	CYP2D6, MTOR, TP53
RALOXIFENE HYDROCHLORIDE	4	BLM, ESR1, TP53
NICARDIPINE HYDROCHLORIDE	4	BLM, CYP2D6, TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	PGR, 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	RECQL, TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	BLM, TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	BLM, RECQL, TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	39	TP53, BRCA1, CHEK2, RET, ROS1, BLM, BRAF, AURKA, TLK2, TOP2A (+29 more)
B	Phased (≥1) drug, not yet approved	6	MSH6, SF3B1, SGK1, ATRIP, MKI67, RB1
C	Druggable family + PDB, no drug	8	PTEN, TIMP1, FCGR2A, FCGR2B, FCGR3A, MTAP, NRG1, NTHL1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	26	BRCA2, PALB2, FANCC, MLH1, MSH2, NF2, PMS2, BARD1, RAD51D, TFF3 (+16 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
PALB2	0	BRCA1
MLH1	0	MSH6
PMS2	1	MSH6
PTEN	8	TP53, AKT1
RAD51D	0	BRCA1
AGR2	0	ESR1
FGF3	0	FGFR1
MRE11	36	BRCA1
NRG1	0	EGFR, ERBB3, ERBB4
FANCC	0	—
MSH2	9	—
NF2	0	—
BARD1	0	—
TFF3	0	—
TIMP1	0	—
XRCC2	0	—
KMT2C	29	—
CDKN1B	5	—
RSF1	0	—
RINT1	0	—
FANCM	0	—
FCGR2A	1	—
FCGR2B	0	—
FCGR3A	0	—
FDXR	0	—
KLLN	0	—
FOXP3	4	—
LZTR1	0	—
MTAP	24	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10,613.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	810
PHASE4	215
PHASE2/PHASE3	75

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
NCT04136782	PHASE4	RECRUITING	Albumin-bound Paclitaxel and Carboplatin Versus Epirubicin and Docetaxel for Triple-negative Breast Cancer
NCT04137640	PHASE4	NOT_YET_RECRUITING	Palbociclib + Letrozole Versus Epirubicin + Cyclophosphamide and Sequential Docetaxel as Neoadjuvant Chemotherapy
NCT04549207	PHASE4	ACTIVE_NOT_RECRUITING	Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-resistant Prostate Cancer
NCT04921137	PHASE4	RECRUITING	Evaluating Harms and Benefits of Endocrine Therapy in Patients ≥70 Years of Age With Lower Risk Breast Cancer
NCT04928261	PHASE4	ACTIVE_NOT_RECRUITING	Evaluating 6-months of HER2-targeted Therapy in Patients With HER2 Positive Early-stage Breast Cancer That Achieve a Pathological Complete Response to Neoadjuvant Systemic Therapy
NCT04929548	PHASE4	NOT_YET_RECRUITING	Exploratory Study of Neoadjuvant Treatment of HER2-positive Breast Cancer With Py in Combination With HP
NCT05161195	PHASE4	ACTIVE_NOT_RECRUITING	Roll-over Study to Allow Continued Access to Ribociclib
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05206331	PHASE4	RECRUITING	CEM to Reduce Biopsy Rates for Less Than Highly Suspicious Breast Abnormalities: a Prospective Study
NCT05333328	PHASE4	RECRUITING	OFS in Premenopausal Node+ Breast Cancer With Low Genomic Risk
NCT05420454	PHASE4	RECRUITING	A Study for the Neoadjuvant Treatment of Breast Cancer
NCT05420467	PHASE4	RECRUITING	A Study for the Adjuvant Treatment of Breast Cancer
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)
NCT05486182	PHASE4	ACTIVE_NOT_RECRUITING	Impact of 18F-FES PET on the Therapeutic Treatment of Patients With Metastatic Breast Cancer
NCT05562518	PHASE4	ACTIVE_NOT_RECRUITING	GRACE-trial: a Randomized Active-controlled Trial for vulvovaGinal atRophy in breAst Cancer Patients on Endocrine Therapy.
NCT05753618	PHASE4	RECRUITING	Evaluating Omission of Granulocyte Colony-stimulating Factors in Breast Cancer Patients Receiving Paclitaxel Portion of Dose-dense Adriamycin-cyclophosphamide and Paclitaxel Chemotherapy
NCT05754528	PHASE4	ACTIVE_NOT_RECRUITING	Evaluating an Endocrine Therapy Dose-frequency Escalation Strategy and Its Effects on Tolerability and Compliance
NCT05841849	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of CINV in Breast Cancer
NCT05860907	PHASE4	NOT_YET_RECRUITING	Clinical Study of Huaier Granules in Patients With Advanced Breast Cancer Without Visceral Metastasis
NCT05871437	PHASE4	NOT_YET_RECRUITING	Randomized Controlled Clinical Study on the Reduction of Tumor Marker Levels in Breast Cancer Patients by Huaier Granules
NCT06072807	PHASE4	RECRUITING	Brain [18F]-FES PET/CT in Patients With Estrogen-Receptor Positive Breast Cancer
NCT06169371	PHASE4	RECRUITING	Abemaciclib Dose Escalation to Maintain Intensity (ADE-MI)
NCT06217185	PHASE4	RECRUITING	The Efficacy and Safety of Pyrotinib, Trastuzumab Combined With Taxanes in the Treatment of Trastuzumab-treated HER2+ Advanced Breast Cancer (ABC).
NCT06245824	PHASE4	NOT_YET_RECRUITING	Trastuzumab Deruxtecan (T-DXd) With Pyrotinib in First-line HER2-positive Unresectable or Metastatic Breast Cancer Trial
NCT06252662	PHASE4	RECRUITING	Liposomal Bupivacaine Vs Bupivacaine with Dexmedetomidine in Erector Spinae Plane Blocks for Mastectomies
NCT06274515	PHASE4	RECRUITING	A Study to Investigate Mechanisms of Resistance to Breast Cancer Therapies
NCT06406127	PHASE4	RECRUITING	Effect of Alpha Lipoic Acid on Chemotherapy Induced Neurological Changes in Breast Cancer Patients
NCT06428682	PHASE4	RECRUITING	Role of TXA in Patients Undergoing Breast Free Flap Reconstruction
NCT06429761	PHASE4	RECRUITING	Phase 4 Study to Assess the Safety of Trastuzumab Deruxtecan, in Indian Patients
NCT06491680	PHASE4	RECRUITING	Cardiotoxicity in Breast Cancer Patients
NCT06574022	PHASE4	RECRUITING	Post-mastectomy Recovery: Comparing Preoperative PECS-II Blocks With Intraoperative Pectoral Blocks
NCT06578299	PHASE4	NOT_YET_RECRUITING	Inetetamab Combined With Paclitaxel With/Without Pertuzumab for Previously Treated HER2-positive Advanced Breast Cancer
NCT06613373	PHASE4	NOT_YET_RECRUITING	An Exploratory Clinical Study of CDK4/6i Dalpiciclib Combined With AI Neoadjuvant Therapy for Stage II-III HR+/HER2- Breast Cancer
NCT06641544	PHASE4	RECRUITING	The Efficacy and Safety of Different Combination Regimens of Inetetamab in First-line Treatment of HER2 Positive Metastatic Breast Cancer
NCT06777537	PHASE4	NOT_YET_RECRUITING	Neoadjuvant Chemotherapy with or Without Talniflumate for the Treatment of Breast Cancer
NCT06920810	PHASE4	RECRUITING	Viscum Album for TNBC on Adjuvant Pembrolizumab
NCT07042581	PHASE4	RECRUITING	A Study of Revaree Plus in People With Breast Cancer
NCT07093931	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Lobaplatin and Carboplatin as Neoadjuvant Therapy in HER-2 Positive Breast Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TAMOXIFEN	4	158
DOCETAXEL ANHYDROUS	4	117
EPIRUBICIN	4	78
GOSERELIN	4	70
TRASTUZUMAB	4	70
DOXORUBICIN	4	65
CYCLOPHOSPHAMIDE ANHYDROUS	4	63
LETROZOLE	4	59
ANASTROZOLE	4	50
FULVESTRANT	4	47
EXEMESTANE	4	40
CAPECITABINE	4	38
ZOLEDRONIC ACID ANHYDROUS	4	38
LAPATINIB	4	33
PERTUZUMAB	4	30
ERIBULIN	4	26
PACLITAXEL	4	26
VINORELBINE	4	26
GEMCITABINE	4	24
PEGFILGRASTIM	4	17
RISEDRONIC ACID	4	16
TRASTUZUMAB EMTANSINE	4	16
FLUOROURACIL	4	15
LEUPROLIDE	4	15
PALBOCICLIB	4	15
FILGRASTIM	4	14
RIBOCICLIB	4	14
BEVACIZUMAB	4	10
CARBOPLATIN	4	10
THIOTEPA	4	9

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 227 predictive associations from 235 curated evidence items; also 50 prognostic, 9 predisposing, 4 oncogenic, 3 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
ERBB2 Amplification	Capecitabine + Lapatinib	Sensitivity/Response	CIViC A	EID11247
ERBB2 Amplification	Lapatinib + Letrozole	Sensitivity/Response	CIViC A	EID11248
ERBB2 Amplification	Margetuximab	Sensitivity/Response	CIViC A	EID11249
ERBB2 Amplification	Trastuzumab + Tucatinib + Capecitabine	Sensitivity/Response	CIViC A	EID11250
ESR1 D538G OR ESR1 Y537C OR ESR1 Y537N OR ESR1 Y537S OR ESR1 E380Q OR ESR1 Mutation	Lasofoxifene	Sensitivity/Response	CIViC A	EID12934
ESR1 Mutation	Elacestrant	Sensitivity/Response	CIViC A	EID11443
PIK3CA C420R	Alpelisib + Fulvestrant	Sensitivity/Response	CIViC A	EID11275
PIK3CA E453K OR PIK3CA E453Q OR PIK3CA E453A OR PIK3CA E453D OR PIK3CA E453G OR PIK3CA E453V	Fulvestrant + Inavolisib + Palbociclib	Sensitivity/Response	CIViC A	EID12540
PIK3CA E542K	Fulvestrant + Alpelisib	Sensitivity/Response	CIViC A	EID7315
PIK3CA E542K OR PIK3CA E542Q OR PIK3CA E542A OR PIK3CA E542D OR PIK3CA E542G OR PIK3CA E542R OR PIK3CA E542V	Palbociclib + Inavolisib + Fulvestrant	Sensitivity/Response	CIViC A	EID12535
PIK3CA E545K OR PIK3CA E545A OR PIK3CA E545G OR PIK3CA E545D	Fulvestrant + Alpelisib	Sensitivity/Response	CIViC A	EID7468
PIK3CA E545K OR PIK3CA E545Q OR PIK3CA E545A OR PIK3CA E545G OR PIK3CA E545V OR PIK3CA E545D OR PIK3CA E545L OR PIK3CA E545R	Palbociclib + Inavolisib + Fulvestrant	Sensitivity/Response	CIViC A	EID12534
PIK3CA G1049S OR PIK3CA G1049R OR PIK3CA G106V OR PIK3CA G106R OR PIK3CA G1049A OR PIK3CA G106S OR PIK3CA G106A OR PIK3CA G106D OR PIK3CA G118D OR PIK3CA G1049C OR PIK3CA G1049D	Palbociclib + Inavolisib + Fulvestrant	Sensitivity/Response	CIViC A	EID12537
PIK3CA H1047R OR PIK3CA H1047Y OR PIK3CA H1047L	Fulvestrant + Alpelisib	Sensitivity/Response	CIViC A	EID7318
PIK3CA H1047R OR PIK3CA H1047Y OR PIK3CA H1047L OR PIK3CA H1047D OR PIK3CA H1047I OR PIK3CA H1047N OR PIK3CA H1047P OR PIK3CA H1047Q OR PIK3CA H1047T	Palbociclib + Inavolisib + Fulvestrant	Sensitivity/Response	CIViC A	EID12533
PIK3CA Mutation	Alpelisib + Fulvestrant	Sensitivity/Response	CIViC A	EID7313
PIK3CA Mutation OR PTEN Mutation OR AKT1 Mutation	Capivasertib + Fulvestrant	Sensitivity/Response	CIViC A	EID12020
PIK3CA N345K OR PIK3CA N345D OR PIK3CA N345H OR PIK3CA N345I OR PIK3CA N345S OR PIK3CA N345T OR PIK3CA N345Y	Palbociclib + Inavolisib + Fulvestrant	Sensitivity/Response	CIViC A	EID12538
PIK3CA Q546E OR PIK3CA Q546R	Fulvestrant + Alpelisib	Sensitivity/Response	CIViC A	EID7316
PIK3CA Q546K OR PIK3CA Q546E OR PIK3CA Q546P OR PIK3CA Q546R OR PIK3CA Q546L OR PIK3CA K111E OR PIK3CA K111N OR PIK3CA K111R OR PIK3CA Q546H	Inavolisib + Fulvestrant + Palbociclib	Sensitivity/Response	CIViC A	EID12536
PIK3CA R88Q OR PIK3CA C420R OR PIK3CA M1043V OR PIK3CA M1043I OR PIK3CA M1043T	Fulvestrant + Palbociclib + Inavolisib	Sensitivity/Response	CIViC A	EID12539
VEGFA Overexpression of VEGF121 and VEGF110	Bevacizumab	Sensitivity/Response	CIViC B	EID9299 +2
ERBB2 Overexpression	Lapatinib	Sensitivity/Response	CIViC B	EID7014 +1
ESR1 Y537N	Palbociclib	Sensitivity/Response	CIViC B	EID4817 +1
ESR1 Y537S	Palbociclib	Sensitivity/Response	CIViC B	EID4819 +1
FGFR1 Amplification	Dovitinib	Sensitivity/Response	CIViC B	EID12478 +1
AKT2 EXPRESSION	Trastuzumab	Sensitivity/Response	CIViC B	EID706
BRAF Wildtype	Cetuximab	Sensitivity/Response	CIViC B	EID11657
BRCA1 Loss-of-function	Talazoparib	Sensitivity/Response	CIViC B	EID4838
BRCA1 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID9019

+197 more predictive associations (showing top 30 by evidence level).