Breast carcinoma

Summary

Breast carcinoma (MONDO:0004989) is a cancer (an umbrella term covering 13 Mondo subtypes) with 61 cohort genes (2,159 GWAS associations across 172 studies; 51 CIViC-evidence somatic drivers; 212 ClinVar predisposition records) and 11,024 clinical trials. The dominant Reactome pathway is PIP3 activates AKT signaling (20 cohort genes). Molecularly, ERBB2 Amplification confers sensitivity to Capecitabine + Lapatinib in Breast Cancer (CIViC Level A); 234 further subtype–drug associations are mapped below. Top therapeutic interventions include tamoxifen, docetaxel anhydrous, and epirubicin.

At a glance

• Classification: Cancer
• Umbrella term: 13 Mondo subtypes
• Cohort genes: 61
• GWAS associations: 2,159
• ClinVar variants: 212
• Clinical trials: 11,024
• Precision-medicine evidence (CIViC): 235 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	breast carcinoma
Mondo ID	MONDO:0004989
EFO	EFO:0000305
DOID	DOID:3459
NCIT	C4872
SNOMED CT	254838004
UMLS	C0678222
MedGen	146260
Anatomy (UBERON)	UBERON:0000310
Is cancer (heuristic)	yes

Also known as: breast cancer · breast cancer, NOS · breast carcinoma · cancer of breast · cancer of the breast · cancer, breast · carcinoma of breast · carcinoma of the breast · mammary carcinoma

Data availability: 212 ClinVar variants · 2,159 GWAS associations (172 studies) · 1 HPO phenotype · 203 cell lines.

Disease family

An umbrella term covering 13 Mondo subtypes.

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

Related subtypes (48): retroperitoneum carcinoma, head and neck carcinoma, peritoneal carcinoma, neuroendocrine carcinoma, laryngeal carcinoma, bone carcinoma, carcinoma ex pleomorphic adenoma, scrotal carcinoma, skin carcinoma, malignant myoepithelioma, trachea carcinoma, epithelial-myoepithelial carcinoma, lipid-rich carcinoma, comedocarcinoma, in situ carcinoma, adenocarcinoma, urinary bladder carcinoma, squamous cell carcinoma, lung carcinoma, prostate carcinoma, renal carcinoma, uterine carcinoma, vulvar carcinoma, large cell carcinoma, undifferentiated carcinoma, basaloid carcinoma, cribriform carcinoma, digestive system carcinoma, fallopian tube carcinoma, penile carcinoma, sarcomatoid carcinoma, thymic carcinoma, transitional cell carcinoma, ureter carcinoma, papillary carcinoma, Krebs 2 carcinoma, thyroid gland carcinoma, vaginal carcinoma, choroid plexus carcinoma, malignant epithelial tumor of ovary, mucin-producing carcinoma, basal cell carcinoma, carcinoma of urethra, combined carcinoid and adenocarcinoma, secondary carcinoma, invasive carcinoma, glycogen-rich carcinoma, lymph node carcinoma

Subtypes (13): nipple carcinoma, bilateral breast carcinoma, female breast carcinoma, sporadic breast cancer, breast carcinoma in situ, breast adenocarcinoma, male breast carcinoma, breast carcinoma by gene expression profile, invasive breast carcinoma, Ehrlich tumor carcinoma, hereditary breast carcinoma, cribriform carcinoma of breast, hormone-resistant breast carcinoma

Genetics & variants

GWAS landscape

2,159 GWAS associations across 172 studies. Top hits map to 19 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs35054928	2e-322	FGFR2	GC	1.27
rs2981578	1e-245	FGFR2	C	1.23
rs4784227	7e-201	CASC16	T	1.23
rs2981579	2e-170	FGFR2	A	1.27
rs78540526	2e-131	LINC01488 - PNCRNA-D	T	0.28
rs3803662	4e-117	CASC16	A	1.24
rs62355901	3e-98	C5orf67 - MAP3K1	C	0.17
rs62355902	7e-98	C5orf67 - MAP3K1	T	1.18
rs4442975	1e-95	TESHL	G	1.12
rs75915166	4e-95	LINC01488 - PNCRNA-D	A	1.28
rs554219	2e-81	LINC01488 - PNCRNA-D	G	1.26
rs2981582	2e-76	FGFR2	A	1.26
rs10941679	6e-73	MRPS30-DT	G	1.15
rs6890270	5e-67	MIER3	G	0.13
rs10096351	2e-64	PCAT1, POU5F1B, CASC8	G	0.11
rs60936670	8e-64	NEK10	C	0.11
rs614367	2e-63	LINC01488 - PNCRNA-D	T	1.21
rs7297051	3e-60	PTHLH - CCDC91	C	1.12
rs930395	2e-58	MRPS30 - HCN1	A	0.12
rs10510097	2e-58	FGFR2	T	0.15
rs13387042	2e-57	TESHL	A	1.14
rs13281615	2e-57	CASC8, POU5F1B, PCAT1	G	1.11
rs4973768	5e-57	SLC4A7	T	1.11
rs630965	3e-54	CHCHD4P2 - RPL36P14	T	0.1
rs60954078	3e-54	CCDC170 - ESR1	G	0.18
rs9397437	5e-54	CCDC170 - ESR1	A	1.17
rs676256	4e-53	CHCHD4P2 - RPL36P14	T	1.1
rs11249433	2e-52	EMBP1	G	1.11
rs10995201	2e-51	LINC02929	A	1.11
rs1696803	2e-45	FGFR2 - ATE1	C	0.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002861	Guo Q	2015	23,059	0	Identification of novel genetic markers of breast cancer survival.
GCST001937	Michailidou K	2013	10,052	12,575	Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
GCST003520	Han MR	2016	7,619	6,286	Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci.
GCST003587	Fehringer G	2016	5,020	61,820	Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
GCST003588	Fehringer G	2016	5,020	61,820	Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
GCST001930	Garcia-Closas M	2013	4,193	35,194	Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
GCST003782	Huo D	2016	3,962	4,150	Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.
GCST001683	Siddiq A	2012	3,666	28,864	A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.
GCST000678	Turnbull C	2010	3,659	4,897	Genome-wide association study identifies five new breast cancer susceptibility loci.
GCST002346	Ahsan H	2014	3,523	2,702	A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	2
Tier 3: regulatory	5
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	0
rare (<0.01)	2
unknown	0

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	14
regulatory_region_variant	5
3_prime_UTR_variant	2
non_coding_transcript_exon_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs35054928	10	121580918	GC>G,GCC	0.4	intron_variant	FGFR2	2e-322	Tier 4: intronic/intergenic
rs2981578	10	121580797	C>A,G,T	0.47	intron_variant	FGFR2	1e-245	Tier 4: intronic/intergenic
rs4784227	16	52565276	C>A,T	0.24	intron_variant	CASC16	7e-201	Tier 4: intronic/intergenic
rs2981579	10	121577821	A>C,G,T	0.4	intron_variant	FGFR2	2e-170	Tier 4: intronic/intergenic
rs78540526	11	69516650	C>T	0.076	regulatory_region_variant	LINC01488 - PNCRNA-D	2e-131	Tier 3: regulatory
rs3803662	16	52552429	A>C,G,T	0.26	non_coding_transcript_exon_variant	CASC16	4e-117	Tier 4: intronic/intergenic
rs62355901	5	56757708	T>A,C,G	0.16	intergenic_variant	C5orf67 - MAP3K1	3e-98	Tier 4: intronic/intergenic
rs62355902	5	56757896	A>C,T	0.16	intergenic_variant	C5orf67 - MAP3K1	7e-98	Tier 4: intronic/intergenic
rs4442975	2	217056046	G>A,C,T	0.5	intron_variant	TESHL	1e-95	Tier 4: intronic/intergenic
rs75915166	11	69564393	C>A	0.06	regulatory_region_variant	LINC01488 - PNCRNA-D	4e-95	Tier 3: regulatory
rs554219	11	69516874	C>A,G,T	0.12	intergenic_variant	LINC01488 - PNCRNA-D	2e-81	Tier 4: intronic/intergenic
rs2981582	10	121592803	A>C,G,T	0.38	intron_variant	FGFR2	2e-76	Tier 4: intronic/intergenic
rs10941679	5	44706396	A>G	0.25	intron_variant	MRPS30-DT	6e-73	Tier 4: intronic/intergenic
rs6890270	5	56964779	A>C,G	0.187	intergenic_variant	MIER3	5e-67	Tier 4: intronic/intergenic
rs10096351	8	127359926	A>C,G,T	0.456	intron_variant	PCAT1, POU5F1B, CASC8	2e-64	Tier 4: intronic/intergenic
rs60936670	3	27290919	CTCAAAACA>C,CTCAAAACATCAAAACA	0.476	intron_variant	NEK10	8e-64	Tier 4: intronic/intergenic
rs614367	11	69513996	C>T	0.15	intergenic_variant	LINC01488 - PNCRNA-D	2e-63	Tier 4: intronic/intergenic
rs7297051	12	28021884	C>G,T	0.24	regulatory_region_variant	PTHLH - CCDC91	3e-60	Tier 3: regulatory
rs930395	5	44822356	G>A,T	0.221	intergenic_variant	MRPS30 - HCN1	2e-58	Tier 4: intronic/intergenic
rs10510097	10	121568362	C>T	0.11	intron_variant	FGFR2	2e-58	Tier 4: intronic/intergenic
rs13387042	2	217041109	A>C,G,T	0.49	intron_variant	TESHL	2e-57	Tier 4: intronic/intergenic
rs13281615	8	127343372	A>C,G,T	0.41	intron_variant	CASC8, POU5F1B, PCAT1	2e-57	Tier 4: intronic/intergenic
rs4973768	3	27374522	C>T	0.47	3_prime_UTR_variant	SLC4A7	5e-57	Tier 2: splice/UTR
rs630965	9	108123199	C>A,G,T	0.38	intergenic_variant	CHCHD4P2 - RPL36P14	3e-54	Tier 4: intronic/intergenic
rs60954078	6	151634779	A>G	0.07	intergenic_variant	CCDC170 - ESR1	3e-54	Tier 4: intronic/intergenic
rs9397437	6	151631197	G>A	0.07	intergenic_variant	CCDC170 - ESR1	5e-54	Tier 4: intronic/intergenic
rs676256	9	108133073	C>A,G,T	0.38	intergenic_variant	CHCHD4P2 - RPL36P14	4e-53	Tier 4: intronic/intergenic
rs11249433	1	121538815	A>C,G,T	0.41	intron_variant	EMBP1	2e-52	Tier 4: intronic/intergenic
rs10995201	10	62540131	A>G	0.16	intron_variant	LINC02929	2e-51	Tier 4: intronic/intergenic
rs1696803	10	121677436	T>A,C	0.163	intergenic_variant	FGFR2 - ATE1	2e-45	Tier 4: intronic/intergenic

ClinVar germline variants

212 retrieved; paginated sample, class counts are floors:

86 pathogenic, 35 conflicting classifications of pathogenicity, 28 pathogenic/likely pathogenic, 24 likely pathogenic, 14 uncertain significance, 12 benign, 8 benign/likely benign, 2 association, 2 likely benign, 1 conflicting classifications of pathogenicity; association; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1192513	NM_000051.4(ATM):c.7424T>G (p.Leu2475Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
1209849	NM_000051.4(ATM):c.6951_6952del (p.Lys2318fs)	ATM	Pathogenic/Likely pathogenic	no assertion criteria provided
1244225	NM_000051.4(ATM):c.6527del (p.Leu2176fs)	ATM	Pathogenic	no assertion criteria provided
127374	NM_000051.4(ATM):c.3802del (p.Glu1267_Val1268insTer)	ATM	Pathogenic	reviewed by expert panel
142700	NM_000051.4(ATM):c.8147T>C (p.Val2716Ala)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
181974	NM_000051.4(ATM):c.6095G>A (p.Arg2032Lys)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
186242	NM_000051.4(ATM):c.8395_8404del (p.Phe2799fs)	ATM	Pathogenic	reviewed by expert panel
230843	NM_000051.4(ATM):c.2497G>T (p.Gly833Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
265585	NM_000051.4(ATM):c.193C>T (p.Gln65Ter)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
584461	NM_000051.4(ATM):c.1110C>A (p.Tyr370Ter)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
647116	NM_000051.4(ATM):c.4383G>A (p.Trp1461Ter)	ATM	Pathogenic	criteria provided, single submitter
847035	NM_000051.4(ATM):c.4019T>A (p.Leu1340Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
936134	NM_000051.4(ATM):c.5755C>T (p.Gln1919Ter)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
229677	NM_000465.4(BARD1):c.1216C>T (p.Arg406Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
125807	NM_007294.4(BRCA1):c.5241del (p.Gly1748fs)	BRCA1	Pathogenic	reviewed by expert panel
17661	NM_007294.4(BRCA1):c.181T>G (p.Cys61Gly)	BRCA1	Pathogenic	reviewed by expert panel
266276	NM_007294.4(BRCA1):c.2536G>T (p.Glu846Ter)	BRCA1	Pathogenic	reviewed by expert panel
266434	NM_007294.4(BRCA1):c.4062_4066del (p.Asn1354fs)	BRCA1	Pathogenic	reviewed by expert panel
266579	NM_007294.4(BRCA1):c.788dup (p.Gly263_Ser264insTer)	BRCA1	Pathogenic	reviewed by expert panel
37426	NM_007294.4(BRCA1):c.1687C>T (p.Gln563Ter)	BRCA1	Pathogenic	reviewed by expert panel
37546	NM_007294.4(BRCA1):c.3770_3771del (p.Glu1257fs)	BRCA1	Pathogenic	reviewed by expert panel
37691	NM_007294.4(BRCA1):c.66dup (p.Glu23fs)	BRCA1	Pathogenic	reviewed by expert panel
495093	NM_007294.4(BRCA1):c.4818del (p.Val1607fs)	BRCA1	Pathogenic	criteria provided, single submitter
54729	NM_007294.4(BRCA1):c.2952del (p.Ile986fs)	BRCA1	Pathogenic	reviewed by expert panel
54764	NM_007294.4(BRCA1):c.3049G>T (p.Glu1017Ter)	BRCA1	Pathogenic	reviewed by expert panel
54944	NM_007294.4(BRCA1):c.3626dup (p.Leu1209fs)	BRCA1	Pathogenic	reviewed by expert panel
55008	NM_007294.4(BRCA1):c.3794del (p.Asn1265fs)	BRCA1	Pathogenic	reviewed by expert panel
55322	NM_007294.4(BRCA1):c.4936del (p.Val1646fs)	BRCA1	Pathogenic	reviewed by expert panel
55344	NM_007294.4(BRCA1):c.4986+6T>G	BRCA1	Pathogenic	reviewed by expert panel
55401	NM_007294.4(BRCA1):c.5102_5103del (p.Leu1701fs)	BRCA1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 209 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 4

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
BRCA2	BRCA2	GWAS, Orphanet
CHEK2	CHEK2	GWAS, Orphanet
TERT	TERT	GWAS, Orphanet
PRC1	PRC1	GWAS

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
CHEK2	Act	BRCA	CIViC #8950
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
TERT	Act	PRCC	CIViC #79
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
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CCNE1			CIViC #11
PALB2	LoF	OVT	CIViC #15013
ERBB4	LoF	BLCA,BRCA,CCRCC,CHOL,COADREAD,ESCA,HCC,MEL,PRAD,STAD	CIViC #1734
ESR1	Act	BRCA,LUSC,MEL,UCEC	CIViC #21
FGF3			CIViC #1873
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37
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
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
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
CD274	LoF	DLBCLNOS	CIViC #11335
CDK6			CIViC #12
CDKN1B	LoF	BRCA,HCC,PCM,PRAD,SIC	CIViC #914
RSF1			CIViC #12121
TUBB3			CIViC #8262
CDK12	LoF	BLCA,CCRCC,CESC,DLBCLNOS,MEL,OVT,PRAD,PROSTATE,STAD	CIViC #12112

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic 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

Cohort genes → proteins

61 cohort genes, 61 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	11
gwas_and_clinvar	2
civic_only	32
multi_evidence	16

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gwas,clinvar,civic_evidence
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	gwas,clinvar,civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar,civic_evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas,clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	gwas,civic_evidence
CCNE1	HGNC:1589	ENSG00000105173	P24864	G1/S-specific cyclin-E1	gwas,civic_evidence
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar,civic_evidence
ERBB4	HGNC:3432	ENSG00000178568	Q15303	Receptor tyrosine-protein kinase erbB-4	gwas,civic_evidence
ESR1	HGNC:3467	ENSG00000091831	P03372	Estrogen receptor	gwas,civic_evidence
FGF3	HGNC:3681	ENSG00000186895	P11487	Fibroblast growth factor 3	gwas,civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gwas,civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar,civic_evidence
PRC1	HGNC:9341	ENSG00000198901	O43663	Protein regulator of cytokinesis 1	gwas,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
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
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
KMT2C	HGNC:13726	ENSG00000055609	Q8NEZ4	Histone-lysine N-methyltransferase 2C	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
CDK12	HGNC:24224	ENSG00000167258	Q9NYV4	Cyclin-dependent kinase 12	civic_evidence
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
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
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
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence
KLLN	HGNC:37212	ENSG00000227268	B2CW77	Killin	civic_evidence
AKT1	HGNC:391	ENSG00000142208	P31749	RAC-alpha serine/threonine-protein kinase	civic_evidence
AKT2	HGNC:392	ENSG00000105221	P31751	RAC-beta serine/threonine-protein kinase	civic_evidence
AKT3	HGNC:393	ENSG00000117020	Q9Y243	RAC-gamma serine/threonine-protein kinase	civic_evidence
MTOR	HGNC:3942	ENSG00000198793	P42345	Serine/threonine-protein kinase mTOR	civic_evidence
ABCB1	HGNC:40	ENSG00000085563	P08183	ATP-dependent translocase ABCB1	civic_evidence
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
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.
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.
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.
FGF3	Fibroblast growth factor 3	Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PRC1	Protein regulator of cytokinesis 1	Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM.
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,…
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.
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…
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).
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.
CDK12	Cyclin-dependent kinase 12	Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation.
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.
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.
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…
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
KLLN	Killin	DNA-binding protein involved in S phase checkpoint control-coupled apoptosis by mediating p53/TP53-induced apoptosis.
AKT1	RAC-alpha serine/threonine-protein kinase	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
AKT2	RAC-beta serine/threonine-protein kinase	Serine/threonine kinase closely related to AKT1 and AKT3.
AKT3	RAC-gamma serine/threonine-protein kinase	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
MTOR	Serine/threonine-protein kinase mTOR	Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
ABCB1	ATP-dependent translocase ABCB1	Translocates drugs and phospholipids across the membrane.
RORA	Nuclear receptor ROR-alpha	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.

Protein-family classification

Druggable: 33 · Difficult: 10 · Unknown: 18 · Druggable fraction: 0.54

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	21	9.5×	1e-14
Nuclear receptor	2	12.7×	0.049
Antibody/Immunoglobulin	4	1.9×	0.468
Transcription factor	9	1.2×	0.713
Phosphatase	1	1.4×	0.819
Transporter	1	1.3×	0.819
Enzyme (other)	4	0.8×	0.977
Other/Unknown	18	0.5×	1.000
Scaffold/PPI	1	0.3×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CCNE1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
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
FGF3	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PRC1	Other/Unknown	no		MAP65_Ase1_PRC1
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
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
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
KMT2C	Transcription factor	no		HMGI/Y_DNA-bd_CS, SET_dom, Znf_RING
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
CDK12	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
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
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
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
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KLLN	Other/Unknown	no
AKT1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
AKT2	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
AKT3	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
MTOR	Kinase	yes		PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
ABCB1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
RORA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt

Expression context

Cohort genes with no expression data: 0.

56 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)	61
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	9
ventricular zone	8
secondary oocyte	6
ganglionic eminence	6
primordial germ cell in gonad	5
oocyte	5
buccal mucosa cell	5
male germ line stem cell (sensu Vertebrata) in testis	4
stromal cell of endometrium	4
adrenal tissue	4
right adrenal gland cortex	4
lower esophagus mucosa	3
upper arm skin	3
endothelial cell	3
right hemisphere of cerebellum	3
sperm	3
sural nerve	3
blood	3
monocyte	3
right adrenal gland	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CCNE1	201	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
ERBB4	226	broad	marker	endothelial cell, secondary oocyte, cranial nerve II
ESR1	216	broad	marker	oviduct epithelium, cervix epithelium, mammalian vulva
FGF3	23	tissue_specific	yes	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PRC1	134	ubiquitous	marker	ventricular zone, ganglionic eminence, primordial germ cell in gonad
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
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
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
KMT2C	261	ubiquitous	marker	oocyte, caput epididymis, upper arm skin
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
CDK6	262	ubiquitous	marker	adrenal tissue, trabecular bone tissue, pylorus
CDKN1B	301	ubiquitous	marker	pigmented layer of retina, retina, ventricular zone
RSF1	280	ubiquitous	marker	calcaneal tendon, tendon, medial globus pallidus
TUBB3	144	ubiquitous	marker	cortical plate, ganglionic eminence, embryo

Protein interactions among cohort

Intra-cohort edges: 105.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
AKT1	16,601
ESR1	12,382
PTEN	11,626
ERBB2	9,659
MTOR	9,490
BRCA1	9,064
PARP1	8,370
CCND1	8,328

Intra-cohort edges

A	B	Sources
ABCB1	CYP2D6	string_interaction
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	FGF3	intact
AKT1	MTOR	intact, string_interaction
AKT1	PIK3CA	biogrid_interaction, string_interaction
AKT1	PTEN	string_interaction
AKT1	RUNX1	intact
AKT1	TBX3	intact
AKT1	TERT	biogrid_interaction
AKT2	AKT3	intact
AKT2	PIK3CA	string_interaction
AKT2	PTEN	string_interaction
AKT3	BRAF	intact
AKT3	PIK3CA	string_interaction
AKT3	PTEN	string_interaction
AKT3	SLC24A3	string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	EGFR	biogrid_interaction
BRAF	FGFR2	biogrid_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TBX3	intact
BRAF	TP53	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	CDK12	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	ESR1	intact, string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	PARP1	string_interaction
BRCA1	RAD51D	string_interaction
BRCA1	TOP2A	intact
BRCA1	TP53	string_interaction
BRCA2	CCND1	intact
BRCA2	CDK12	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	PARP1	string_interaction
BRCA2	RAD51D	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
CCND1	CDK6	intact, string_interaction
CCND1	CDKN1B	biogrid_interaction, intact, string_interaction
CCND1	ESR1	string_interaction
CCND1	TP53	string_interaction
CCNE1	CDK6	string_interaction

Structural data

PDB: 54 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ESR1	P03372	478
EGFR	P00533	388
TP53	P04637	313
PIK3CA	P42336	135
BRAF	P15056	131
PARP1	P09874	106
FGFR1	P11362	83
CD274	Q9NZQ7	76
SF3B1	O75533	74
MTOR	P42345	70
FGFR2	P21802	63
ERBB2	P04626	63
AKT1	P31749	43
CDK12	Q9NYV4	39
CHEK2	O96017	38
RET	P07949	34
BRCA1	P38398	33
TUBB3	Q13509	28
ABCB1	P08183	24
TERT	O14746	23
ERBB3	P21860	23
CCNE1	P24864	22
CDK6	Q00534	22
CDKN1B	P46527	19
AKT2	P31751	19
RAD51D	O75771	17
TOP2A	P11388	15
FCGR3A	P08637	15
FGFR3	P22607	15
BRCA2	P51587	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FDXR	P22570	91.66
TAGLN	Q01995	88.63
FGF3	P11487	79.32
SLC24A3	Q9HC58	70.31
RPS6KC1	Q96S38	56.74
KLLN	B2CW77	51.20
RSF1	Q96T23	48.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 979. Enrichment computed across 250 evidence-associated genes (152 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 152 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PIP3 activates AKT signaling	20	8.8×	9e-11	ERBB4, ESR1, FGF3, FGFR2, PIK3CA, SGK1, CDKN1B, RNF146 (+12 more)
Constitutive Signaling by Aberrant PI3K in Cancer	13	10.8×	8e-08	ERBB4, ESR1, FGF3, FGFR2, PIK3CA, EGFR, ERBB2, ERBB3 (+5 more)
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	14	8.9×	2e-07	ERBB4, ESR1, FGF3, FGFR2, PIK3CA, EGFR, ERBB2, ERBB3 (+6 more)
PI3K Cascade	9	16.1×	8e-07	FGF3, FGFR2, PIK3CA, FGF10, FGF19, FGF4, FGFR1, FGFR3 (+1 more)
Mitotic G1 phase and G1/S transition	10	12.1×	2e-06	CCND1, CCNE1, MCM8, CDK6, CDKN1B, CDKN2A, CDKN2B, AKT1 (+2 more)
Impaired BRCA2 binding to PALB2	7	21.0×	3e-06	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, EXO1
Resolution of D-loop Structures through Holliday Junction Intermediates	8	15.8×	3e-06	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, MUS81, EXO1
RAF/MAP kinase cascade	15	6.0×	3e-06	ERBB4, FGF3, FGFR2, PIK3CA, RET, BRAF, RANBP9, EGFR (+7 more)
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	7	19.5×	4e-06	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, EXO1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	7	19.5×	4e-06	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, EXO1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	7	19.5×	4e-06	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, EXO1
Regulation of TP53 Degradation	8	15.4×	4e-06	CHEK2, TP53, SGK1, CDKN2A, AKT1, AKT2, AKT3, MTOR
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	7	18.1×	6e-06	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, EXO1
MITF-M-regulated melanocyte development	11	8.3×	6e-06	BRCA1, TERT, CCND1, TBX3, TCF7L2, TFAP2A, CDH1, CDH2 (+3 more)
Homologous DNA Pairing and Strand Exchange	7	17.5×	6e-06	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, EXO1
Downregulation of ERBB2 signaling	7	17.5×	6e-06	ERBB4, EGFR, ERBB2, ERBB3, AKT1, AKT2, AKT3
MITF-M-dependent gene expression	9	10.7×	8e-06	BRCA1, TERT, CCND1, TCF7L2, TFAP2A, CDH1, CDH2, CDKN2A (+1 more)
Signaling by ERBB2	7	15.9×	1e-05	ERBB4, EGFR, ERBB2, ERBB3, AKT1, AKT2, AKT3
Cell Cycle	18	4.3×	1e-05	BRCA2, BRCA1, TERT, CCND1, CCNE1, MCM8, CDK6, CDKN1B (+10 more)
Regulation of TP53 Expression and Degradation	6	20.5×	2e-05	SGK1, CDKN2A, AKT1, AKT2, AKT3, MTOR
Downregulation of ERBB2:ERBB3 signaling	5	26.8×	3e-05	ERBB2, ERBB3, AKT1, AKT2, AKT3
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	6	17.3×	4e-05	CCND1, CDKN1B, EGFR, AKT1, AKT2, AKT3
HDR through Homologous Recombination (HRR)	8	10.0×	5e-05	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, BRIP1, MUS81, EXO1
G1 Phase	6	15.5×	8e-05	CCND1, CCNE1, CDK6, CDKN1B, CDKN2A, CDKN2B
PI3K events in ERBB2 signaling	5	22.1×	8e-05	ERBB4, PIK3CA, EGFR, ERBB2, ERBB3
Extra-nuclear estrogen signaling	8	9.0×	1e-04	CCND1, ESR1, PIK3CA, CDKN1B, EGFR, AKT1, AKT2, AKT3
G1/S Transition	7	10.7×	1e-04	CCND1, CCNE1, MCM8, CDKN1B, AKT1, AKT2, AKT3
Gene expression (Transcription)	24	2.8×	1e-04	BRCA1, CCND1, CCNE1, RORA, RUNX1, SF3B1, SGK1, STK11 (+16 more)
FLT3 Signaling	6	13.7×	1e-04	PIK3CA, CDKN1B, SH2B3, AKT1, AKT2, AKT3
PI-3K cascade:FGFR1	5	17.1×	3e-04	FGF3, PIK3CA, FGF10, FGF4, FGFR1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 223 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA damage response	19	4.6×	8e-05	CHEK2, BRCA1, TP53, CCND1, SGK1, STK11, TLK2, TOP2A (+11 more)
telomere maintenance	9	10.8×	1e-04	TERT, CCNE1, RAD51D, LTO1, DCLRE1B, ZNF365, PARP1, MUS81 (+1 more)
pancreas development	6	18.1×	5e-04	HNF1A, HNF1B, TCF7L2, ZNF808, FGF10, FOXF1
heart development	14	4.9×	5e-04	TERT, ERBB4, PTEN, TBX5, TGFBR2, CASP8, TAB2, CDKN1B (+6 more)
double-strand break repair via homologous recombination	10	7.0×	6e-04	BRCA2, BRCA1, PALB2, RAD51D, XRCC2, FBH1, MCM8, HELQ (+2 more)
positive regulation of transcription by RNA polymerase II	35	2.3×	7e-04	BRCA1, TP53, ESR1, FGFR2, PTEN, RORA, RUNX1, ATXN1 (+27 more)
epidermal growth factor receptor signaling pathway	8	8.9×	7e-04	ERBB4, PIK3CA, BRAF, GAREM1, EGFR, ERBB2, ERBB3, AKT1
in utero embryonic development	14	4.5×	7e-04	TP53, FGFR2, TBX3, TGFBR2, XRCC2, DHX35, ZMIZ1, OTUD7B (+6 more)
positive regulation of MAPK cascade	13	4.7×	9e-04	ERBB4, FGF3, FGFR2, RET, CDH2, EGFR, ERBB2, ERBB3 (+5 more)
positive regulation of DNA-templated transcription	23	2.9×	0.001	BRCA2, CHEK2, BRCA1, TP53, ERBB4, ESR1, RET, RORA (+15 more)
cellular response to epidermal growth factor stimulus	7	10.0×	0.001	ERBB4, CFL1, COL1A1, GAREM1, EGFR, ERBB2, AKT1
response to UV-A	3	56.7×	0.001	CCND1, EGFR, AKT1
cellular senescence	7	9.3×	0.001	BRCA2, TP53, TBX3, ZMIZ1, CDKN1B, CDKN2A, CDKN2B
fibroblast growth factor receptor signaling pathway	7	9.0×	0.002	FGF3, FGFR2, FGF10, FGF19, FGF4, FGFR1, FGFR3
double-strand break repair	8	7.3×	0.002	BRCA2, CHEK2, BRCA1, TP53, BRIP1, BABAM1, PARP1, MUS81
positive regulation of G1/S transition of mitotic cell cycle	6	10.8×	0.002	TERT, CCND1, CCNE1, EGFR, FGF10, AKT1
anoikis	4	23.2×	0.002	PIK3CA, STK11, AKT1, MTOR
positive regulation of phospholipase activity	3	45.3×	0.002	FGFR2, FGFR1, FGFR3
negative regulation of apoptotic process	19	3.0×	0.003	TP53, PALB2, ERBB4, SIAH2, BRAF, TBX3, TFAP2A, TIMP1 (+11 more)
positive regulation of epithelial cell proliferation	7	7.7×	0.003	ERBB4, FGFR2, TCF7L2, EGFR, ERBB2, ERBB3, FGF10
antibody-dependent cellular cytotoxicity	3	37.8×	0.004	FCGR2A, FCGR2B, FCGR3A
replicative senescence	4	17.8×	0.005	CHEK2, TERT, TP53, CDKN2A
positive regulation of stem cell proliferation	5	11.8×	0.005	TERT, TBX3, FGF10, FGF4, FGFR1
negative regulation of transcription by RNA polymerase II	28	2.2×	0.005	TP53, CCND1, CCNE1, ESR1, FGFR2, RUNX1, ATXN1, TBX3 (+20 more)
branching morphogenesis of a nerve	3	32.4×	0.005	FGFR2, DLX2, FGF13
resolution of meiotic recombination intermediates	4	16.8×	0.005	TOP2A, ANKLE1, MUS81, ERCC4
embryonic digestive tract morphogenesis	4	16.8×	0.005	FGFR2, HNF1B, FGF10, FOXF1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	5	11.1×	0.005	BRCA2, CHEK2, TP53, HIPK1, ATAD5
stem cell proliferation	6	8.4×	0.005	TP53, TBX3, FGF10, FGF4, FGFR1, ABCB1
response to X-ray	4	15.9×	0.006	BRCA2, TP53, CCND1, XRCC2

Therapeutics

Drugs indicated for this disease

23 approved, 34 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)
Denosumab	Approved (phase 4)
Estradiol	Approved (phase 4)
Everolimus	Approved (phase 4)
Exemestane	Approved (phase 4)
Fulvestrant	Approved (phase 4)
Ixabepilone	Approved (phase 4)
Letrozole	Approved (phase 4)
Methotrexate	Approved (phase 4)
Olaparib	Approved (phase 4)
Paclitaxel	Approved (phase 4)
Palbociclib	Approved (phase 4)
Pertuzumab	Approved (phase 4)
TECHNETIUM TC 99M SULFUR COLLOID	Approved (phase 4)
Trastuzumab	Approved (phase 4)
Trastuzumab Deruxtecan	Approved (phase 4)
Trastuzumab Emtansine	Approved (phase 4)
Tucatinib	Approved (phase 4)
Bicalutamide	Phase 3 (in late-stage trials)
Busulfan	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)
Cisplatin	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Elacestrant	Phase 3 (in late-stage trials)
Entinostat	Phase 3 (in late-stage trials)
Enzalutamide	Phase 3 (in late-stage trials)
Eribulin	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Goserelin	Phase 3 (in late-stage trials)
Lapatinib	Phase 3 (in late-stage trials)
Leuprolide	Phase 3 (in late-stage trials)
Lidocaine	Phase 3 (in late-stage trials)
Neratinib	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Pegfilgrastim	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Progesterone	Phase 3 (in late-stage trials)
Ribociclib	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Sulfur Hexafluoride	Phase 3 (in late-stage trials)
Talazoparib	Phase 3 (in late-stage trials)
Tamoxifen	Phase 3 (in late-stage trials)
Temsirolimus	Phase 3 (in late-stage trials)
Thiotepa	Phase 3 (in late-stage trials)
Triptorelin	Phase 3 (in late-stage trials)
Veliparib	Phase 3 (in late-stage trials)
Vinorelbine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alisertib, Binimetinib, Bintrafusp Alfa, Bortezomib, Bosutinib, Caffeine, Cediranib, Ceralasertib, Cimetidine, Cobimetinib, Copanlisib, Cyanocobalamin, Dasatinib Anhydrous, Degarelix, Diphenhydramine, Famotidine, Fluocinonide, Fluoroestradiol, Folic Acid, Ipilimumab, Loperamide, Metformin, Omeprazole, Panitumumab, Patritumab Deruxtecan, Pelareorep, Perflutren, Pralatrexate, Racemetyrosine, Ranitidine, Retifanlimab, Ruxolitinib, Simvastatin, Tipifarnib, Tivantinib, Trametinib, Tremelimumab, Vismodegib.

Drug target analysis

Approved (phase 4): 32 · Phase ≥3: 33 · Phased (≥1): 35 · Undrugged: 26

Druggability breadth: 94 of 250 evidence-associated genes (38%) 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
CHEK2	NERATINIB
BRCA1	RIBOFLAVIN
TERT	BERBERINE
TP53	NITROFURANTOIN
CCND1	PALBOCICLIB
CCNE1	PALBOCICLIB
ERBB4	MOBOCERTINIB
ESR1	CANDESARTAN CILEXETIL
FGFR2	PONATINIB
PIK3CA	IDELALISIB
RET	PONATINIB
BRAF	VEMURAFENIB
TLK2	FEDRATINIB
TOP2A	IDARUBICIN
CD274	MOCLOBEMIDE
CDK6	PALBOCICLIB
TUBB3	COLCHICINE
CYP2D6	LEVOSALBUTAMOL
PARP1	NIRAPARIB
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
ERBB3	MOBOCERTINIB
FGFR1	PONATINIB
FGFR3	PONATINIB
AKT1	CAPIVASERTIB
AKT2	CAPIVASERTIB
AKT3	CAPIVASERTIB
MTOR	SALMETEROL XINAFOATE
ABCB1	PROGESTERONE
RORA	TRETINOIN
RUNX1	APOMORPHINE HYDROCHLORIDE
STK11	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP2D6	436	4
TP53	196	4
EGFR	175	4
MTOR	164	4
ESR1	162	4
RET	135	4
ABCB1	119	4
FGFR1	93	4
ERBB2	83	4
PIK3CA	67	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NERATINIB	4	CHEK2, EGFR, ERBB2, ERBB3, ERBB4
BOSUTINIB	4	CHEK2, EGFR, ERBB2, ERBB3, ERBB4, RET
BRIGATINIB	4	CHEK2, EGFR, ERBB2, ERBB4, FGFR1, FGFR2
SUNITINIB	4	AKT2, CHEK2, EGFR, FGFR1, FGFR2, FGFR3
GEFITINIB	4	ABCB1, BRAF, CHEK2, EGFR, ERBB2, ERBB3
RIBOFLAVIN	4	BRCA1, CYP2D6
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	ABCB1, BRCA1, ESR1, TOP2A, TP53
DOXORUBICIN HYDROCHLORIDE	4	ABCB1, BRCA1, TOP2A
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ABCB1, BRCA1, CYP2D6
BERBERINE	4	CYP2D6, TERT
DOXORUBICIN	4	ABCB1, ERBB2, ESR1, TERT, TOP2A
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	ESR1, TP53
DIENESTROL	4	CYP2D6, ESR1, TP53
CLOTRIMAZOLE	4	ABCB1, CYP2D6, EGFR, ERBB2, TP53
COLCHICINE	4	CYP2D6, TP53, TUBB3
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	MTOR, TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	CYP2D6, MTOR, TP53
RALOXIFENE HYDROCHLORIDE	4	ESR1, TP53
NICARDIPINE HYDROCHLORIDE	4	CYP2D6, TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 26.

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
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
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
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
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
TERT	391	Binding:389, Functional:2
CDK12	347	Binding:341, Functional:6
STK11	244	Binding:244
TLK2	185	Binding:185
ERBB3	169	Binding:169
RORA	115	Binding:111, Functional:3, Unclassified:1
KMT2C	29	Binding:29
SF3B1	22	Binding:22
RPS6KC1	22	Binding:22
RUNX1	20	Binding:17, Functional:3
BRCA1	13	Binding:9, Functional:4
PTEN	8	Binding:8
CDKN1B	5	Binding:5
FCGR2A	1	Binding:1
SLC4A7	1	Binding:1
TBX5	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
ERBB4	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
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
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
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
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
CDK12	2.7.11.22, 2.7.11.23	cyclin-dependent kinase, [RNA-polymerase]-subunit 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
FGFR1	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
ST8SIA4	2.4.99.8	alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
STK11	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHEK2	690
TERT	391
TP53	869
CCND1	576
CCNE1	691
ERBB4	591
ESR1	2,435
FGFR2	966
PIK3CA	2,034
RET	1,586
SGK1	538
BRAF	1,442
TLK2	185
TOP2A	1,305
CD274	525
CDK6	715
TUBB3	1,781
CDK12	347
CYP2D6	3,659
PARP1	825
EGFR	6,531
ERBB2	1,221
ERBB3	169
FGFR1	1,465
FGFR3	975
AKT1	1,942
AKT2	822
AKT3	660
MTOR	1,375
ABCB1	3,063

Pharmacogenomics

Cohort genes with a PharmGKB record: 61; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CYP2D6	1

Drug repurposing candidates

29 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
NERATINIB	4	CHEK2, EGFR, ERBB2, ERBB3, ERBB4
BOSUTINIB	4	CHEK2, EGFR, ERBB2, ERBB3, ERBB4, RET
BRIGATINIB	4	CHEK2, EGFR, ERBB2, ERBB4, FGFR1, FGFR2
SUNITINIB	4	AKT2, CHEK2, EGFR, FGFR1, FGFR2, FGFR3
GEFITINIB	4	ABCB1, BRAF, CHEK2, EGFR, ERBB2, ERBB3
RIBOFLAVIN	4	BRCA1, CYP2D6
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	ABCB1, BRCA1, ESR1, TOP2A, TP53
DOXORUBICIN HYDROCHLORIDE	4	ABCB1, BRCA1, TOP2A
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ABCB1, BRCA1, CYP2D6
BERBERINE	4	CYP2D6, TERT
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	ESR1, TP53
DIENESTROL	4	CYP2D6, ESR1, TP53
CLOTRIMAZOLE	4	ABCB1, CYP2D6, EGFR, ERBB2, TP53
COLCHICINE	4	CYP2D6, TP53, TUBB3
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	MTOR, TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	CYP2D6, MTOR, TP53
RALOXIFENE HYDROCHLORIDE	4	ESR1, TP53
NICARDIPINE HYDROCHLORIDE	4	CYP2D6, TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	32	CHEK2, BRCA1, TERT, TP53, CCND1, CCNE1, ERBB4, ESR1, FGFR2, PIK3CA (+22 more)
B	Phased (≥1) drug, not yet approved	3	SF3B1, SGK1, CDK12
C	Druggable family + PDB, no drug	6	PTEN, TIMP1, FCGR2A, FCGR2B, FCGR3A, ST8SIA4
D	Druggable family + AlphaFold only, no drug	1	RPS6KC1
E	Difficult family or no structure, no drug	19	BRCA2, PALB2, FGF3, PRC1, RAD51D, TFF3, KMT2C, CDKN1B, RSF1, AGR2 (+9 more)

Undrugged target profiles

26 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
FGF3	0	FGFR1
PTEN	8	STK11, TP53, AKT1
RAD51D	0	BRCA1
AGR2	0	ESR1
PRC1	0	—
TFF3	0	—
TIMP1	0	—
KMT2C	29	—
CDKN1B	5	—
RSF1	0	—
FCGR2A	1	—
FCGR2B	0	—
FCGR3A	0	—
FDXR	0	—
KLLN	0	—
RPS6KC1	22	—
ATXN1	0	—
SIAH2	0	—
ST8SIA4	0	—
SLC24A3	0	—
SLC4A7	1	—
TAGLN	0	—
TBX3	0	—
TBX5	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11,024.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	805
PHASE4	216
PHASE2/PHASE3	79

Top trials by phase / activity

NCT	Phase	Status	Title
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
NCT05376878	PHASE4	RECRUITING	An Investigational Scan (64Cu-DOTA-Trastuzumab PET/MRI) in Imaging Patients With HER2+ Breast Cancer With Brain Metastasis
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	156
DOCETAXEL ANHYDROUS	4	117
EPIRUBICIN	4	76
GOSERELIN	4	73
TRASTUZUMAB	4	71
DOXORUBICIN	4	65
CYCLOPHOSPHAMIDE ANHYDROUS	4	63
LETROZOLE	4	60
ANASTROZOLE	4	50
FULVESTRANT	4	47
EXEMESTANE	4	41
CAPECITABINE	4	38
ZOLEDRONIC ACID ANHYDROUS	4	38
LAPATINIB	4	33
PERTUZUMAB	4	31
ERIBULIN	4	26
PACLITAXEL	4	26
VINORELBINE	4	25
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: 235 predictive associations from 243 curated evidence items; also 51 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
ESR1 Mutation	Imlunestrant Regimen + Abemaciclib Regimen	Sensitivity/Response	CIViC A	EID12599
ESR1 Mutation	Aromatase Inhibitor + Fulvestrant + Imlunestrant Regimen	Sensitivity/Response	CIViC A	EID12600
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

+205 more predictive associations (showing top 30 by evidence level).