Prostate carcinoma

Summary

Prostate carcinoma (MONDO:0005159) is a cancer (an umbrella term covering 9 Mondo subtypes) with 65 cohort genes (2,976 GWAS associations across 116 studies; 20 CIViC-evidence somatic drivers) and 5,473 clinical trials. The dominant Reactome pathway is Abacavir transmembrane transport (3 cohort genes). Molecularly, BRCA1 Mutation confers sensitivity to Olaparib in Prostate Cancer (CIViC Level A); 48 further subtype–drug associations are mapped below. Top therapeutic interventions include goserelin, leuprolide, and bicalutamide.

At a glance

• Classification: Cancer
• Umbrella term: 9 Mondo subtypes
• Cohort genes: 65
• GWAS associations: 2,976
• Clinical trials: 5,473
• Precision-medicine evidence (CIViC): 49 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prostate carcinoma
Mondo ID	MONDO:0005159
EFO	EFO:0001663
DOID	DOID:10286
NCIT	C4863
UMLS	C0600139
MedGen	108657
Anatomy (UBERON)	UBERON:0002367
Is cancer (heuristic)	yes

Also known as: cancer of prostate · cancer of the prostate · carcinoma of prostate · carcinoma of prostate gland · carcinoma of the prostate · prostate cancer · prostate cancer, NOS · prostate carcinoma · prostate gland carcinoma

Data availability: 2,976 GWAS associations (116 studies) · 513 cell lines.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › prostate 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, breast carcinoma, squamous cell carcinoma, lung 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 (9): prostate squamous cell carcinoma, primary prostate urothelial carcinoma, metastatic prostate carcinoma, prostate adenocarcinoma, grade III prostatic intraepithelial neoplasia, prostate small cell carcinoma, familial prostate carcinoma, hormone-resistant prostate carcinoma, castration-resistant prostate carcinoma

Genetics & variants

GWAS landscape

2,976 GWAS associations across 116 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs10993994	9e-192	MSMB	T	1.21
rs11263763	1e-183	HNF1B	A	1.21
rs1447295	1e-179	CASC8	A	1.41
rs183373024	4e-160	PCAT1, CASC19, PRNCR1	G	2.91
rs77541621	5e-147	PCAT1	A	1.89
rs4430796	1e-132	HNF1B	A	1.22
rs11228580	5e-125	SMIM38 - MYEOV	C	1.27
rs1160267	9e-123	SINHCAFP3 - NKX3-1	G	1.17
rs4646284	6e-121	SLC22A1 - SLC22A2	TG	1.2
rs6983267	1e-113	PCAT1, CASC8, POU5F1B, CCAT2	G	1.17
rs148511027	1e-105	CASC17	G	1.16
rs78416326	5e-99	PRKCI - SKIL	G	1.21
rs1859962	1e-91	CASC17	G	1.17
rs72725879	1e-90	PCAT1, PRNCR1, CASC19	T	1.29
rs7931342	1e-86	SMIM38 - MYEOV	G	1.17
rs11338635	7e-85	LINC01496	GA	1.1
rs7463326	2e-82	PCAT1	G	1.18
rs72725854	4e-82	PCAT1	T	2.09
rs5945619	1e-73	LINC01496	C	1.11
rs11043143	2e-73	MIR4686 - ASCL2	T	1.16
rs5759167	6e-71	RPS25P10 - BIK	G	1.15
rs7127900	5e-68	MIR4686 - ASCL2	A	1.19
rs138213197	9e-63	HOXB13	T	3.85
rs76765083	2e-62	KLK3	T	1.3
rs58235267	7e-62	OTX1	G	1.12
rs7837688	2e-58	CASC8 - CASC11	T	1.73
rs113925811	5e-58	KRT8	A	1.18
rs77167534	1e-55	ITGA6	C	1.24
rs2242652	8e-55	TERT	G	1.14
rs339351	3e-53	RFX6	C	1.12

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST006085	Schumacher FR	2018	79,148	61,106	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
GCST006084	Schumacher FR	2018	61,978	0	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
GCST002606	Al Olama AA	2014	34,379	33,164	A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
GCST006082	Schumacher FR	2018	20,658	0	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
GCST006080	Schumacher FR	2018	15,561	0	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
GCST006083	Schumacher FR	2018	15,167	58,308	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
GCST006081	Schumacher FR	2018	14,160	0	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
GCST001942	Eeles RA	2013	11,085	11,463	Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
GCST003100	Szulkin R	2015	7,322	0	Genome-wide association study of prostate cancer-specific survival.
GCST006089	Schumacher FR	2018	6,988	44,256	Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	1
rare (<0.01)	1
unknown	1

Functional consequences

Consequence	Count
intron_variant	31
intergenic_variant	10
non_coding_transcript_exon_variant	4
regulatory_region_variant	2
splice_donor_region_variant	1
TF_binding_site_variant	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs10993994	10	46046326	A>G	0.05	intergenic_variant	MSMB	9e-192	Tier 4: intronic/intergenic
rs11263763	17	37743574	A>C,G	0.05	intron_variant	HNF1B	1e-183	Tier 4: intronic/intergenic
rs1447295	8	127472793	A>C,G,T	0.11	intron_variant	CASC8	1e-179	Tier 4: intronic/intergenic
rs183373024	8	127091872	A>G	0.01	non_coding_transcript_exon_variant	PCAT1, CASC19, PRNCR1	4e-160	Tier 4: intronic/intergenic
rs77541621	8	127064901	G>A	0.05	intron_variant	PCAT1	5e-147	Tier 4: intronic/intergenic
rs4430796	17	37738049	A>C,G,T	0.47	intron_variant	HNF1B	1e-132	Tier 4: intronic/intergenic
rs11228580	11	69234875	T>C	0.05	splice_donor_region_variant	SMIM38 - MYEOV	5e-125	Tier 2: splice/UTR
rs1160267	8	23672008	G>A,C,T	0.05	intron_variant	SINHCAFP3 - NKX3-1	9e-123	Tier 4: intronic/intergenic
rs4646284	6	160160512	T>TG	0.05	intron_variant	SLC22A1 - SLC22A2	6e-121	Tier 4: intronic/intergenic
rs6983267	8	127401060	G>T	0.05	non_coding_transcript_exon_variant	PCAT1, CASC8, POU5F1B, CCAT2	1e-113	Tier 4: intronic/intergenic
rs148511027	17	71121392			intron_variant	CASC17	1e-105	Tier 4: intronic/intergenic
rs78416326	3	170356729	G>C	0.05	non_coding_transcript_exon_variant	PRKCI - SKIL	5e-99	Tier 4: intronic/intergenic
rs1859962	17	71112612	G>C,T	0.48	intron_variant	CASC17	1e-91	Tier 4: intronic/intergenic
rs72725879	8	127091724	C>G,T	0.05	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	1e-90	Tier 4: intronic/intergenic
rs7931342	11	69227030	T>G	0.5	intron_variant	SMIM38 - MYEOV	1e-86	Tier 4: intronic/intergenic
rs11338635	X	51502425	GA>G	0.05	intron_variant	LINC01496	7e-85	Tier 4: intronic/intergenic
rs7463326	8	127015709	G>A,C	0.05	intron_variant	PCAT1	2e-82	Tier 4: intronic/intergenic
rs72725854	8	127062570	A>G,T	0.061	intron_variant	PCAT1	4e-82	Tier 4: intronic/intergenic
rs5945619	X	51498820	C>A,T	0.36	intergenic_variant	LINC01496	1e-73	Tier 4: intronic/intergenic
rs11043143	11	2212863	T>A,C,G	0.05	regulatory_region_variant	MIR4686 - ASCL2	2e-73	Tier 3: regulatory
rs5759167	22	43104206	G>A,T	0.5	TF_binding_site_variant	RPS25P10 - BIK	6e-71	Tier 3: regulatory
rs7127900	11	2212344	A>C,G,T	0.2	intergenic_variant	MIR4686 - ASCL2	5e-68	Tier 4: intronic/intergenic
rs138213197	17	48728343	C>T	0.002	missense_variant	HOXB13	9e-63	Tier 1: coding
rs76765083	19	50859459	T>A,C,G	0.05	intron_variant	KLK3	2e-62	Tier 4: intronic/intergenic
rs58235267	2	63050708	C>A,G,T	0.05	regulatory_region_variant	OTX1	7e-62	Tier 3: regulatory
rs7837688	8	127527115	T>A,C,G	0.158	intergenic_variant	CASC8 - CASC11	2e-58	Tier 4: intronic/intergenic
rs113925811	12	52915148	C>A,T	0.05	intron_variant	KRT8	5e-58	Tier 4: intronic/intergenic
rs77167534	2	172455202	C>G,T	0.05	intron_variant	ITGA6	1e-55	Tier 4: intronic/intergenic
rs2242652	5	1279913	G>A	0.05	intron_variant	TERT	8e-55	Tier 4: intronic/intergenic
rs339351	6	116879271	C>A	0.05	intron_variant	RFX6	3e-53	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 104 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 5

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

Gene	HGNC	Evidence routes
BRCA2	BRCA2	GWAS, Orphanet
CHEK2	CHEK2	GWAS, Orphanet
HOXB13	HOXB13	GWAS, Orphanet
ATM	ATM	GWAS, Orphanet
HNF1B	HNF1B	GWAS, Orphanet

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
HOXB13			CIViC #8351
IGF2			CIViC #60
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
TYMS			CIViC #5971
CFLAR			CIViC #7009
CDK12	LoF	BLCA,CCRCC,CESC,DLBCLNOS,MEL,OVT,PRAD,PROSTATE,STAD	CIViC #12112
PALB2	LoF	OVT	CIViC #15013
RRM2			CIViC #5052
SIX1	Act	WT
ZFP36L1	Act	BLCA,MLYM	CIViC #625
SOX9	LoF	COAD,COADREAD
SPOP	Act	NHL,PRAD,PROSTATE,UCEC,UCS	CIViC #6652
TCF4	LoF	MBL,PAST
TCF7L2	LoF	COAD,COADREAD,HCC,READ
TERT	Act	PRCC	CIViC #79
TMPRSS2	Act	PRAD	CIViC #5813

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
HOXB13	Orphanet:1331	Familial prostate cancer
IGF2	Orphanet:2128	Isolated hemihyperplasia
IGF2	Orphanet:231117	Beckwith-Wiedemann syndrome due to imprinting defect of 11p15
IGF2	Orphanet:231140	Silver-Russell syndrome due to an imprinting defect of 11p15
IGF2	Orphanet:231144	Silver-Russell syndrome due to 11p15 microduplication
IGF2	Orphanet:397590	Silver-Russell syndrome due to a point mutation
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia
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
STK11	Orphanet:2869	Peutz-Jeghers syndrome
TYMS	Orphanet:1775	Dyskeratosis congenita
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
PALB2	Orphanet:84	Fanconi anemia
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
TSHZ1	Orphanet:141074	External auditory canal aplasia/hypoplasia

Cohort genes → proteins

65 cohort genes, 64 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	54
civic_only	6
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gwas,civic_evidence
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	gwas,civic_evidence
HOXB13	HGNC:5112	ENSG00000159184	Q92826	Homeobox protein Hox-B13	gwas,civic_evidence
IGF2	HGNC:5466	ENSG00000167244	P01344	Insulin-like growth factor 2	gwas,civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	gwas,civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	civic_evidence
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	civic_evidence
TYMS	HGNC:12441	ENSG00000176890	P04818	Thymidylate synthase	civic_evidence
CFLAR	HGNC:1876	ENSG00000003402	O15519	CASP8 and FADD-like apoptosis regulator	civic_evidence
CDK12	HGNC:24224	ENSG00000167258	Q9NYV4	Cyclin-dependent kinase 12	civic_evidence
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	civic_evidence
RNF5	HGNC:10068	ENSG00000204308	Q99942	E3 ubiquitin-protein ligase RNF5	gwas
BCYRN1	HGNC:1022	ENSG00000236824		brain cytoplasmic RNA 1	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	gwas
CNNM3	HGNC:104	ENSG00000168763	Q8NE01	Metal transporter CNNM3	gwas
RPS21	HGNC:10409	ENSG00000171858	P63220	Small ribosomal subunit protein eS21	gwas
RRM2	HGNC:10452	ENSG00000171848	P31350	Ribonucleoside-diphosphate reductase subunit M2	gwas
BIK	HGNC:1051	ENSG00000100290	Q13323	Bcl-2-interacting killer	gwas
SALL3	HGNC:10527	ENSG00000256463	Q9BXA9	Sal-like protein 3	gwas
TSHZ1	HGNC:10669	ENSG00000179981	Q6ZSZ6	Teashirt homolog 1	gwas
SHC1	HGNC:10840	ENSG00000160691	P29353	SHC-transforming protein 1	gwas
BOK	HGNC:1087	ENSG00000176720	Q9UMX3	Bcl-2-related ovarian killer protein	gwas
SIX1	HGNC:10887	ENSG00000126778	Q15475	Homeobox protein SIX1	gwas
SKIL	HGNC:10897	ENSG00000136603	P12757	Ski-like protein	gwas
SKIC2	HGNC:10898	ENSG00000204351	Q15477	Superkiller complex protein 2	gwas
SLC22A1	HGNC:10963	ENSG00000175003	O15245	Solute carrier family 22 member 1	gwas
SLC22A2	HGNC:10966	ENSG00000112499	O15244	Solute carrier family 22 member 2	gwas
SLC22A3	HGNC:10967	ENSG00000146477	O75751	Solute carrier family 22 member 3	gwas
ZFP36L1	HGNC:1107	ENSG00000185650	Q07352	mRNA decay activator protein ZFP36L1	gwas
BSN	HGNC:1117	ENSG00000164061	Q9UPA5	Protein bassoon	gwas
SOX9	HGNC:11204	ENSG00000125398	P48436	Transcription factor SOX-9	gwas
SPOP	HGNC:11254	ENSG00000121067	O43791	Speckle-type POZ protein	gwas
SREBF1	HGNC:11289	ENSG00000072310	P36956	Sterol regulatory element-binding protein 1	gwas
SRMS	HGNC:11298	ENSG00000125508	Q9H3Y6	Tyrosine-protein kinase Srms	gwas
STC2	HGNC:11374	ENSG00000113739	O76061	Stanniocalcin-2	gwas
WHR1	HGNC:11398	ENSG00000204344	P49842	Winged helix repair factor 1	gwas
STK25	HGNC:11404	ENSG00000115694	O00506	Serine/threonine-protein kinase 25	gwas
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
STYX	HGNC:11447	ENSG00000198252	Q8WUJ0	Serine/threonine/tyrosine-interacting protein	gwas
TAF1B	HGNC:11533	ENSG00000115750	Q53T94	TATA box-binding protein-associated factor RNA polymerase I subunit B	gwas
TBL1X	HGNC:11585	ENSG00000101849	O60907	F-box-like/WD repeat-containing protein TBL1X	gwas
TBX1	HGNC:11592	ENSG00000184058	O43435	T-box transcription factor TBX1	gwas
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	gwas
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	gwas
TCF4	HGNC:11634	ENSG00000196628	P15884	Transcription factor 4	gwas
TCF7L2	HGNC:11641	ENSG00000148737	Q9NQB0	Transcription factor 7-like 2	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TH	HGNC:11782	ENSG00000180176	P07101	Tyrosine 3-monooxygenase	gwas
KLF11	HGNC:11811	ENSG00000172059	O14901	Krueppel-like factor 11	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.
HOXB13	Homeobox protein Hox-B13	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
IGF2	Insulin-like growth factor 2	The insulin-like growth factors possess growth-promoting activity.
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
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.
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
TYMS	Thymidylate synthase	Catalyzes the reductive methylation of 2’-deoxyuridine 5’-monophosphate (dUMP) to thymidine 5’-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to…
CFLAR	CASP8 and FADD-like apoptosis regulator	Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells.
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.
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.
RNF5	E3 ubiquitin-protein ligase RNF5	Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
CFB	Complement factor B	Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
CNNM3	Metal transporter CNNM3	Probable metal transporter.
RPS21	Small ribosomal subunit protein eS21	Component of the small ribosomal subunit.
RRM2	Ribonucleoside-diphosphate reductase subunit M2	Provides the precursors necessary for DNA synthesis.
BIK	Bcl-2-interacting killer	Accelerates programmed cell death.
SALL3	Sal-like protein 3	Probable transcription factor.
TSHZ1	Teashirt homolog 1	Probable transcriptional regulator involved in developmental processes.
SHC1	SHC-transforming protein 1	Signaling adapter that couples activated growth factor receptors to signaling pathways.
BOK	Bcl-2-related ovarian killer protein	Apoptosis regulator that functions through different apoptotic signaling pathways.
SIX1	Homeobox protein SIX1	Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development.
SKIL	Ski-like protein	May have regulatory role in cell division or differentiation in response to extracellular signals.
SKIC2	Superkiller complex protein 2	Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways.
SLC22A1	Solute carrier family 22 member 1	Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
SLC22A2	Solute carrier family 22 member 2	Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
SLC22A3	Solute carrier family 22 member 3	Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
ZFP36L1	mRNA decay activator protein ZFP36L1	Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthes…
BSN	Protein bassoon	Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released.
SOX9	Transcription factor SOX-9	Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
SPOP	Speckle-type POZ protein	Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation.
SREBF1	Sterol regulatory element-binding protein 1	Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane.
SRMS	Tyrosine-protein kinase Srms	Non-receptor tyrosine-protein kinase which phosphorylates DOK1 on tyrosine residues.
STC2	Stanniocalcin-2	Has an anti-hypocalcemic action on calcium and phosphate homeostasis.
WHR1	Winged helix repair factor 1	DNA-binding protein which is required for efficient transcription-coupled nucleotide excision repair (TC-NER).
STK25	Serine/threonine-protein kinase 25	Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress.
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
STYX	Serine/threonine/tyrosine-interacting protein	Catalytically inactive phosphatase.
TAF1B	TATA box-binding protein-associated factor RNA polymerase I subunit B	Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment ev…
TBL1X	F-box-like/WD repeat-containing protein TBL1X	F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units.
TBX1	T-box transcription factor TBX1	Transcription factor that plays a key role in cardiovascular development by promoting pharyngeal arch segmentation during embryonic development.
TBX5	T-box transcription factor TBX5	DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3’.
TCF4	Transcription factor 4	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
TCF7L2	Transcription factor 7-like 2	Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TH	Tyrosine 3-monooxygenase	Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of catecholamines, dopamine, noradrenaline, and adrenaline.
KLF11	Krueppel-like factor 11	Transcription factor.
TMPRSS2	Transmembrane protease serine 2	Plasma membrane-anchored serine protease that cleaves at arginine residues.

Protein-family classification

Druggable: 21 · Difficult: 22 · Unknown: 22 · Druggable fraction: 0.32

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
Transcription factor	18	2.3×	0.005
Kinase	6	2.6×	0.147
Transporter	3	3.6×	0.171
Complement	1	4.1×	0.524
Protease	3	1.7×	0.524
Antibody/Immunoglobulin	3	1.4×	0.643
Phosphatase	1	1.3×	0.677
Scaffold/PPI	4	1.1×	0.677
Enzyme (other)	4	0.7×	0.891
Other/Unknown	22	0.6×	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
HOXB13	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
IGF2	Other/Unknown	no		IGF2_C, Insulin-like, IGF2
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TYMS	Enzyme (other)	yes	2.1.1.45	Thymidylate_synthase, Thymidylate_synthase_AS, Thymidate_synth/dCMP_Mease_dom
CFLAR	Other/Unknown	no		Pept_C14_p20, DED_dom, DEATH-like_dom_sf
CDK12	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
RNF5	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
BCYRN1	Other/Unknown	no
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
CNNM3	Other/Unknown	no		CBS_dom, CNNM, Ion_transp-like_CBS
RPS21	Other/Unknown	no		Ribosomal_eS21, Ribosomal_eS21_CS, Ribosomal_eS21_sf
RRM2	Enzyme (other)	yes	1.17.4.1	RNR_small_fam, Ferritin-like_SF, RNR-like
BIK	Other/Unknown	no		Bcl2_BH3_motif_CS, Bcl2-int_killer
SALL3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
TSHZ1	Transcription factor	no		HD, Znf_C2H2_type, Teashirt_fam
SHC1	Scaffold/PPI	no		SH2, PID_Shc-like, PTB/PI_dom
BOK	Other/Unknown	no		Bcl2-like, Bcl-2_fam, Bcl-2-like_sf
SIX1	Transcription factor	no		HD, KN_HD, Homeodomain-like_sf
SKIL	Other/Unknown	no		SKI/SNO/DAC, DNA-bd_dom_put_sf, SAND-like_dom_sf
SKIC2	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Ski2/MTR4_C
SLC22A1	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC22A2	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC22A3	Transporter	yes		Orgcat_transp/SVOP, Sugar_transporter_CS, MFS
ZFP36L1	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf
BSN	Transcription factor	no		Znf_piccolo, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
SOX9	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_sf
SPOP	Other/Unknown	no		BTB/POZ_dom, MATH/TRAF_dom, TRAF-like
SREBF1	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf
SRMS	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
STC2	Other/Unknown	no		Stanniocalcin
WHR1	Other/Unknown	no		STK19-like
STK25	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
STYX	Phosphatase	yes		Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, TYR_PHOSPHATASE_DUAL_dom
TAF1B	Transcription factor	no		TF_Rrn7_Zf, TAF1B/Rrn7, Rrn7_cyclin_C
TBL1X	Scaffold/PPI	no		WD40_rpt, LisH, Quinoprotein_ADH-like_sf
TBX1	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TBX5	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
TCF4	Transcription factor	no	7.6.2.3	bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TCF7L2	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TH	Enzyme (other)	yes	1.14.16.2	ArAA_hydroxylase, Tyr_3_mOase, ArAA_hydroxylase_Fe/CU_BS
KLF11	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf

Expression context

Cohort genes with no expression data: 0.

57 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)	65
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	7
male germ line stem cell (sensu Vertebrata) in testis	6
secondary oocyte	6
sural nerve	6
primordial germ cell in gonad	5
right adrenal gland	5
right lobe of liver	5
lower esophagus mucosa	4
hindlimb stylopod muscle	4
oocyte	4
liver	4
calcaneal tendon	3
buccal mucosa cell	3
adult mammalian kidney	3
stromal cell of endometrium	3
left adrenal gland	3
right adrenal gland cortex	3
mucosa of sigmoid colon	2
adrenal tissue	2
placenta	2

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
HOXB13	38	broad	marker	rectum, mucosa of sigmoid colon, prostate gland
IGF2	135	ubiquitous	marker	adrenal tissue, placenta, sural nerve
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
TYMS	262	ubiquitous	marker	ventricular zone, embryo, trabecular bone tissue
CFLAR	290	ubiquitous	marker	right lung, apex of heart, upper lobe of left lung
CDK12	259	ubiquitous	marker	buccal mucosa cell, sural nerve, secondary oocyte
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
RNF5	134	ubiquitous	marker	ganglionic eminence, adult mammalian kidney, cortical plate
BCYRN1	133		marker	primary visual cortex, superior frontal gyrus, temporal lobe
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland
CFB	134	broad	marker	right lobe of liver, liver, gall bladder
CNNM3	250	ubiquitous	marker	gastrocnemius, muscle of leg, cerebellar hemisphere
RPS21	295	ubiquitous	marker	nipple, penis, trabecular bone tissue
RRM2	233	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
BIK	192	broad	marker	nasal cavity epithelium, olfactory segment of nasal mucosa, palpebral conjunctiva
SALL3	74	broad	marker	ventricular zone, ganglionic eminence, amygdala
TSHZ1	255	ubiquitous	marker	jejunal mucosa, cerebellar vermis, ileal mucosa
SHC1	291	ubiquitous	marker	stromal cell of endometrium, gall bladder, omental fat pad
BOK	231	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, inferior vagus X ganglion
SIX1	188	ubiquitous	marker	skeletal muscle tissue of biceps brachii, biceps brachii, parotid gland
SKIL	280	ubiquitous	marker	tendon of biceps brachii, mucosa of paranasal sinus, tendon
SKIC2	134	ubiquitous	yes	right lobe of liver, pituitary gland, adenohypophysis
SLC22A1	163	tissue_specific	marker	right lobe of liver, liver, cartilage tissue
SLC22A2	108	tissue_specific	marker	adult mammalian kidney, nephron tubule, renal medulla
SLC22A3	189	broad	marker	thoracic aorta, ascending aorta, descending thoracic aorta
ZFP36L1	289	ubiquitous	marker	mucosa of paranasal sinus, endocervix, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 31.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
ATM	7,383
TBL1X	6,393
SPOP	5,899
TERT	5,717
PALB2	5,641
STK11	5,146
SOX9	4,935
BRCA2	4,839
CHEK2	4,795

Intra-cohort edges

A	B	Sources
ARHGEF5	SHC1	biogrid_interaction, intact, string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CDK12	string_interaction
ATM	CHEK2	string_interaction
ATM	STK11	string_interaction
ATP9B	SALL3	string_interaction
BIK	BOK	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	CDK12	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	HOXB13	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	CDK12	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	HOXB13	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	STK11	string_interaction
C2	SKIC2	string_interaction
C2	WHR1	string_interaction
CDK12	PALB2	string_interaction
CHEK2	PALB2	string_interaction
HNF1B	KLF11	string_interaction
HOXB13	PALB2	string_interaction
PALB2	STK11	string_interaction
RNF5	UBE2E2	biogrid_interaction, intact
SKIC2	WHR1	string_interaction
SPOP	TMPRSS2	string_interaction
SPOP	WHR1	intact
TNXB	WHR1	string_interaction
VAMP5	VAMP8	string_interaction

Structural data

PDB: 49 · AlphaFold-only: 15 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS21	P63220	209
TYMS	P04818	61
CDK12	Q9NYV4	39
CHEK2	O96017	38
SPOP	O43791	36
TMPRSS2	O15393	34
BRCA1	P38398	33
CFB	P00751	26
TERT	O14746	23
CFLAR	O15519	17
IGF2	P01344	16
SLC22A1	O15245	16
BRCA2	P51587	14
ATM	Q13315	14
C2	P06681	14
C4A	P0C0L4	12
SHC1	P29353	11
SKIC2	Q15477	11
HOXB13	Q92826	10
UBE2E2	Q96LR5	10
TNFRSF6B	O95407	8
CNNM2	Q9H8M5	7
CNNM3	Q8NE01	7
TH	P07101	7
RRM2	P31350	5
WHR1	P49842	5
TCF4	P15884	5
STK11	Q15831	4
PALB2	Q86YC2	4
STC2	O76061	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BTNL2	Q9UIR0	85.97
SRMS	Q9H3Y6	83.99
VAMP5	O95183	80.60
TNXA	Q16473	80.33
ATP9B	O43861	79.49
TAF1B	Q53T94	79.35
TPD52L2	O43399	70.10
RNF5	Q99942	68.71
RBMS3	Q6XE24	63.30
BIK	Q13323	62.38
ZNF236	Q9UL36	55.21
TSHZ1	Q6ZSZ6	54.57
KLF11	O14901	49.73
ARHGEF5	Q12774	48.84
BSN	Q9UPA5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 784. Enrichment computed across 250 evidence-associated genes (137 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 137 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Abacavir transmembrane transport	3	50.0×	0.007	SLC22A1, SLC22A2, SLC22A3
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	5	14.4×	0.007	BRCA2, ATM, BRCA1, RTEL1, PALB2
Cell Cycle	14	3.7×	0.007	BRCA2, ATM, BRCA1, TERT, SUN2, ADRM1, RTEL1, CCNH (+6 more)
Resolution of D-Loop Structures	4	18.5×	0.010	BRCA2, ATM, BRCA1, RTEL1
Homology Directed Repair	5	11.3×	0.010	BRCA2, ATM, BRCA1, RTEL1, BABAM1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	11.3×	0.010	BRCA2, ATM, BRCA1, RTEL1, BABAM1
Abacavir ADME	3	31.3×	0.010	SLC22A1, SLC22A2, SLC22A3
Activation of C3 and C5	3	27.8×	0.013	CFB, C2, C4A
Impaired BRCA2 binding to PALB2	4	13.3×	0.017	BRCA2, ATM, BRCA1, PALB2
DNA Double-Strand Break Repair	5	9.1×	0.017	BRCA2, ATM, BRCA1, RTEL1, BABAM1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	4	12.3×	0.017	BRCA2, ATM, BRCA1, PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	4	12.3×	0.017	BRCA2, ATM, BRCA1, PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	4	12.3×	0.017	BRCA2, ATM, BRCA1, PALB2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	3	20.8×	0.018	BRCA2, ATM, BRCA1
Cellular responses to stress	12	3.2×	0.018	ATM, RPS21, SHC1, BRCA1, TBL1X, ADRM1, ACTR1A, CDKN1B (+4 more)
Homologous DNA Pairing and Strand Exchange	4	11.1×	0.021	BRCA2, ATM, BRCA1, PALB2
Signaling by TCF7L2 mutants	2	41.7×	0.024	TCF7L2, CTBP2
Diseases of DNA Double-Strand Break Repair	3	17.9×	0.024	BRCA2, ATM, BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	3	17.9×	0.024	BRCA2, ATM, BRCA1
SLC-mediated transport of organic cations	3	16.7×	0.024	SLC22A1, SLC22A2, SLC22A3
R-HSA-549132	3	16.7×	0.024	SLC22A1, SLC22A2, SLC22A3
Stabilization of p53	3	16.7×	0.024	CHEK2, ATM, ADRM1
p53-Dependent G1 DNA Damage Response	3	15.6×	0.024	ATM, ADRM1, CDKN1B
p53-Dependent G1/S DNA damage checkpoint	3	15.6×	0.024	ATM, ADRM1, CDKN1B
Reproduction	5	7.0×	0.024	BRCA2, ATM, BRCA1, SUN2, TET2
HDR through Homologous Recombination (HRR)	5	7.0×	0.024	BRCA2, ATM, BRCA1, RTEL1, PALB2
Signaling by Hedgehog	5	6.7×	0.024	SPOP, ADRM1, SUFU, BOC, TUBA1C
Gene expression (Transcription)	18	2.3×	0.024	ATM, SKIL, BRCA1, SOX9, SREBF1, STK11, TAF1B, TBL1X (+10 more)
TP53 Regulates Transcription of DNA Repair Genes	5	6.6×	0.025	ATM, BRCA1, NELFE, CCNH, CDK12
G1/S DNA Damage Checkpoints	3	14.7×	0.027	ATM, ADRM1, CDKN1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 224 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
purine-containing compound transmembrane transport	3	75.2×	0.003	SLC22A1, SLC22A2, SLC22A3
spermidine transport	3	56.4×	0.004	SLC22A1, SLC22A2, SLC22A3
obsolete epinephrine transport	3	56.4×	0.004	SLC22A1, SLC22A2, SLC22A3
obsolete serotonin transport	3	45.1×	0.008	SLC22A1, SLC22A2, SLC22A3
obsolete organic cation transport	3	28.2×	0.029	SLC22A1, SLC22A2, SLC22A3
dopamine uptake	3	28.2×	0.029	SLC22A1, SLC22A2, SLC22A3
heart development	11	3.9×	0.029	ATM, SHC1, ZFP36L1, SOX9, TBX1, TBX5, TERT, TH (+3 more)
acetylcholine transport	2	75.2×	0.029	SLC22A1, SLC22A2
obsolete norepinephrine transport	3	25.1×	0.029	SLC22A1, SLC22A2, SLC22A3
positive regulation of protein localization to nucleus	5	8.8×	0.037	STK11, TCF7L2, TRIM8, FERMT2, YAP1
obsolete dopamine transport	3	20.5×	0.043	SLC22A1, SLC22A2, SLC22A3
serotonin uptake	3	20.5×	0.043	SLC22A1, SLC22A2, SLC22A3
putrescine transport	2	50.1×	0.044	SLC22A1, SLC22A2
histamine transport	2	50.1×	0.044	SLC22A2, SLC22A3
regulation of branch elongation involved in ureteric bud branching	2	50.1×	0.044	SIX1, HNF1B
ureter smooth muscle cell differentiation	2	50.1×	0.044	SIX1, SOX9
positive regulation of secondary heart field cardioblast proliferation	2	50.1×	0.044	SIX1, TBX5
intrinsic apoptotic signaling pathway in response to DNA damage	5	7.2×	0.050	CHEK2, ATM, BOK, SKIL, BRCA1
regulation of transcription by RNA polymerase II	34	1.8×	0.059	HOXB13, SALL3, TSHZ1, SIX1, BRCA1, SREBF1, TBL1X, TBX1 (+26 more)
histamine uptake	2	37.6×	0.060	SLC22A2, SLC22A3
thiamine transmembrane transport	2	37.6×	0.060	SLC22A1, SLC22A2
cellular detoxification	3	15.1×	0.060	SLC22A1, SLC22A2, SLC22A3
regulation of autophagosome assembly	3	15.1×	0.060	CHEK2, ATM, RNF5
cellular senescence	5	6.6×	0.060	BRCA2, ATM, ZMIZ1, CDKN1B, CDKN2B
skeletal muscle tissue development	5	6.5×	0.060	SIX1, SKIL, VAMP5, ERO1A, CFLAR
riboflavin metabolic process	2	30.1×	0.073	SLC52A3, FLAD1
quaternary ammonium group transport	2	30.1×	0.073	SLC22A1, SLC22A3
soft palate development	2	30.1×	0.073	TSHZ1, TBX1
diphosphoinositol polyphosphate metabolic process	2	30.1×	0.073	NUDT10, NUDT11
diadenosine pentaphosphate catabolic process	2	30.1×	0.073	NUDT10, NUDT11

Therapeutics

Drugs indicated for this disease

11 approved, 17 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
AUTOLOGOUS PERIPHERAL-BLOOD MONONUCLEAR CELLS INCLUDING A MINIMUM OF 50 MILLION AUTOLOGOUS CD54+ CELLS ACTIVATED WITH PROSTATIC ACID PHOSPHATASE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR	Approved (phase 4)
Abiraterone Acetate	Approved (phase 4)
Apalutamide	Approved (phase 4)
Cabazitaxel	Approved (phase 4)
Darolutamide	Approved (phase 4)
Dutasteride	Approved (phase 4)
Enzalutamide	Approved (phase 4)
Finasteride	Approved (phase 4)
Flutamide	Approved (phase 4)
Isopropyl Alcohol	Approved (phase 4)
Olaparib	Approved (phase 4)
Abiraterone	Phase 3 (in late-stage trials)
Bicalutamide	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Degarelix	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Epoetin Alfa	Phase 3 (in late-stage trials)
Goserelin	Phase 3 (in late-stage trials)
Hydrocortisone	Phase 3 (in late-stage trials)
Leuprolide	Phase 3 (in late-stage trials)
Mitoxantrone	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Perflutren	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Sipuleucel-T	Phase 3 (in late-stage trials)
Tasquinimod	Phase 3 (in late-stage trials)
Triptorelin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aspirin, Bortezomib, Calcitriol, Carboplatin, Durvalumab, Erdafitinib, Estradiol, Estrogens, Conjugated, Golimumab, Hyaluronidase, Ipilimumab, Ketoconazole, Metformin, Methylphenidate, Niraparib, Pertuzumab, QS-21, Rilimogene Galvacirepvec, Sargramostim, Siltuximab, Simvastatin, Sinecatechins, Testosterone, Testosterone Cypionate, Testosterone Enanthate, Tivantinib, Trametinib, Trastuzumab, Tremelimumab, Vandetanib, Veliparib, Vorinostat.

Drug target analysis

Approved (phase 4): 15 · Phase ≥3: 17 · Phased (≥1): 20 · Undrugged: 45

Druggability breadth: 81 of 250 evidence-associated genes (32%) 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
ATM	AMIODARONE HYDROCHLORIDE
BRCA1	RIBOFLAVIN
STK11	FEDRATINIB
TYMS	FOLIC ACID
CFB	IPTACOPAN
RPS21	GENTAMICIN SULFATE
SLC22A1	PROGESTERONE
SLC22A2	PROGESTERONE
SLC22A3	PROGESTERONE
SREBF1	CALCIFEDIOL ANHYDROUS
SRMS	FEDRATINIB
STK25	FEDRATINIB
TERT	BERBERINE
TMPRSS2	DEBRISOQUIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC22A1	86	4
SLC22A2	47	4
ATM	35	4
CHEK2	30	4
SLC22A3	20	4
SRMS	19	4
STK25	18	4
STK11	17	4
CDK12	17	3
BRCA1	12	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NERATINIB	4	CHEK2, STK25
BOSUTINIB	4	CHEK2, SRMS, STK25
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2, SLC22A1, STK11, STK25
GEFITINIB	4	CHEK2
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM, BRCA1, SLC22A1, SLC22A2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

Symbol	Assays	Type breakdown
CHEK2	690	Binding:687, Functional:2, ADMET:1
TERT	391	Binding:389, Functional:2
TYMS	376	Binding:373, ADMET:2, Functional:1
CDK12	347	Binding:341, Functional:6
STK11	244	Binding:244
ATM	240	Binding:233, Functional:5, ADMET:2
STK25	211	Binding:211
SRMS	179	Binding:178, Functional:1
SLC22A2	101	Functional:62, ADMET:21, Binding:18
SLC22A1	97	Functional:41, Binding:35, ADMET:21
RPS21	90	Binding:90
SPOP	82	Binding:82
RRM2	37	Binding:34, Functional:3
WHR1	36	Binding:36
CFB	33	Binding:33
SLC22A3	33	Binding:17, Functional:11, ADMET:5
TCF4	31	Binding:31
TMPRSS2	28	Binding:28
TCF7L2	22	Binding:22
SREBF1	17	Binding:17
BRCA1	13	Binding:9, Functional:4
SIX1	12	Binding:12
ERO1A	12	Binding:12
SHC1	10	Binding:10
TBL1X	9	Binding:9
TH	8	Binding:8
TAF1B	6	Binding:6
CFLAR	4	Binding:4
C2	4	Binding:4
SOX9	3	Binding:3
RNF5	2	Binding:2
TBX5	1	Binding:1
TPD52L2	1	Binding:1
VAMP8	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
TYMS	2.1.1.45	thymidylate synthase
CDK12	2.7.11.22, 2.7.11.23	cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
CFB	3.4.21.47	alternative-complement-pathway C3/C5 convertase
RRM2	1.17.4.1	ribonucleoside-diphosphate reductase
SRMS	2.7.10.2	non-specific protein-tyrosine kinase
TCF4	7.6.2.3	ABC-type glutathione-S-conjugate transporter
TH	1.14.16.2	tyrosine 3-monooxygenase
TMPRSS2	3.4.21.B60
UBE2E2	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHEK2	690
ATM	240
STK11	244
TYMS	376
CDK12	347
SLC22A2	101
SRMS	179
STK25	211
TERT	391

Pharmacogenomics

Cohort genes with a PharmGKB record: 65; with CPIC/DPWG dosing guidelines: 0.

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

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)
NERATINIB	4	CHEK2, STK25
BOSUTINIB	4	CHEK2, SRMS, STK25
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2, SLC22A1, STK11, STK25
GEFITINIB	4	CHEK2
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM, BRCA1, SLC22A1, SLC22A2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	15	CHEK2, ATM, BRCA1, STK11, TYMS, CFB, RPS21, SLC22A1, SLC22A2, SLC22A3 (+5 more)
B	Phased (≥1) drug, not yet approved	5	CDK12, RRM2, TAF1B, TCF4, ERO1A
C	Druggable family + PDB, no drug	6	STYX, TH, TNXB, UBE2E2, C2, C4A
D	Druggable family + AlphaFold only, no drug	2	BTNL2, TNXA
E	Difficult family or no structure, no drug	37	BRCA2, HOXB13, IGF2, CFLAR, PALB2, RNF5, BCYRN1, CNNM2, CNNM3, BIK (+27 more)

Undrugged target profiles

45 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
HOXB13	0	—
IGF2	0	—
CFLAR	4	—
RNF5	2	—
BCYRN1	0	—
CNNM2	0	—
CNNM3	0	—
BIK	0	—
SALL3	0	—
TSHZ1	0	—
SHC1	10	—
BOK	0	—
SIX1	12	—
SKIL	0	—
SKIC2	0	—
ZFP36L1	0	—
BSN	0	—
SOX9	3	—
SPOP	82	—
STC2	0	—
WHR1	36	—
BTNL2	0	—
STYX	0	—
TBL1X	9	—
TBX1	0	—
TBX5	1	—
HNF1B	0	—
TCF7L2	22	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5,473.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	430
PHASE2	424
PHASE4	99
PHASE1/PHASE2	80
PHASE2/PHASE3	67

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03016741	PHASE4	ACTIVE_NOT_RECRUITING	Cognitive Effects of Androgen Receptor Directed Therapies for Advanced Prostate Cancer
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
NCT05457257	PHASE4	ACTIVE_NOT_RECRUITING	Clinical Study to Assess the Efficacy and Safety of Olaparib in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations
NCT05629494	PHASE4	RECRUITING	Anti-inflammatory Drugs and Serum Prostate-Specific Antigen Test
NCT05722925	PHASE4	ACTIVE_NOT_RECRUITING	Evaluating Fluciclovine PET in Patients With Biochemical Recurrence of Prostate Cancer and a Negative PSMA PET
NCT05753046	PHASE4	ENROLLING_BY_INVITATION	Laparoscopic TAP Block During Robotic Assisted Laparoscopic Radical Prostatectomy for Improvement in Postoperative Pain
NCT05803941	PHASE4	RECRUITING	Long-Term Safety of Lutetium (177Lu) Vipivotide Tetraxetan in Participants With Prostate Cancer
NCT05805436	PHASE4	RECRUITING	Preop Laxatives in Robotic Urologic Surgery
NCT05919329	PHASE4	RECRUITING	Evaluation of the Change in PSMA Expression in Prostate Cancer in Response to Hormonal Therapy
NCT05957822	PHASE4	RECRUITING	Goal-directed vs Preemptive Tranexamic Acid Administration in Non-cardiac Surgery
NCT06001619	PHASE4	RECRUITING	Prostate Medication, Metabolism and Gut Microbiota
NCT06074510	PHASE4	ACTIVE_NOT_RECRUITING	PYLARIFY® PET/CT or PET/MRI in Men With Favorable Intermediate Risk (FIR) Prostate Cancer
NCT06099093	PHASE4	RECRUITING	Pilot of 18F-DCFPyL-PSMA PET in mCRPC Patients Receiving 117Lu-Vipivotide Tetraxetan
NCT06226129	PHASE4	RECRUITING	Gadopiclenol in Contrast Enhanced MRI of the Prostate
NCT06627530	PHASE4	ACTIVE_NOT_RECRUITING	COACTION Trial - COmbination Androgen bloCkade in inTermediate to hIgh-risk prOstate caNcer
NCT06660862	PHASE4	NOT_YET_RECRUITING	Evaluating Treatment Outcomes Using Darolutamide and Androgen Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer.
NCT06733350	PHASE4	RECRUITING	Testosterone Replacement Therapy for the Treatment of Low Testosterone in Hypogonadal Men With Localized Prostate Cancer on Active Surveillance
NCT06784986	PHASE4	RECRUITING	Impact of Using the Airseal System With Ultra-low Pneumoperitoneum in Patients Undergoing Robot-assisted Radical Prostatectomy: A Prospective, Comparative, Randomized Clinical Study.
NCT06908694	PHASE4	RECRUITING	Investigation of GLP1-Receptor Agonists in Men With Prostate Cancer Taking Androgen Deprivation Therapy
NCT07001709	PHASE4	RECRUITING	Determining the Effect of Abiraterone on the Metabolism of Oxycodone in Men With Prostate Cancer (the ENABLE Study)
NCT07278362	PHASE4	NOT_YET_RECRUITING	Testosterone Replacement Therapy in Hypogonadal Patients With Prostate Cancer Under Active Surveillance
NCT07569926	PHASE4	NOT_YET_RECRUITING	Impact of Fluciclovine (18F) PET (Positron Emission Tomography) on the Management of Prostate Cancer Following Negative or Equivocal PSMA (Prostate-Specific Membrane Antigen) PET Imaging at the Time of Biochemical Recurrence
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00220194	PHASE4	COMPLETED	A Six-Month, Open-Label, Crossover Study Of the Maintenance Of Serum Testosterone And PSA Suppression After Switching Between Lupron 22.5 Mg And Eligard 22.5 Mg Or Zoladex 10.8 Mg And Eligard 22.5 Mg In Patients With Advanced Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GOSERELIN	4	122
LEUPROLIDE	4	119
BICALUTAMIDE	4	65
TALAZOPARIB	4	57
ZOLEDRONIC ACID ANHYDROUS	4	56
DOCETAXEL ANHYDROUS	4	45
DEGARELIX	4	41
TRIPTORELIN	4	36
ENZALUTAMIDE	4	33
ABIRATERONE ACETATE	4	32
FLUTAMIDE	4	32
MITOXANTRONE	4	23
ESTRAMUSTINE PHOSPHATE SODIUM	4	21
ABIRATERONE	4	17
KETOCONAZOLE	4	15
LEVOKETOCONAZOLE	4	15
APALUTAMIDE	4	14
GONADORELIN	4	13
CABAZITAXEL	4	11
CALCITRIOL	4	11
DAROLUTAMIDE	4	9
DUTASTERIDE	4	9
SARGRAMOSTIM	4	8
GALLIUM GA 68 GOZETOTIDE	4	7
NILUTAMIDE	4	7
IXABEPILONE	4	6
PIFLUFOLASTAT F18	4	6
RELUGOLIX	4	6
SIPULEUCEL-T	4	6
VINORELBINE TARTRATE	4	6

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 49 predictive associations from 62 curated evidence items; also 13 prognostic, 6 predisposing, 5 diagnostic, 4 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
BRCA1 Mutation	Olaparib	Sensitivity/Response	CIViC A	EID12943 +2
BRCA2 Mutation	Olaparib	Sensitivity/Response	CIViC A	EID12942 +2
BRCA1 Mutation AND BRCA2 Mutation	Olaparib	Sensitivity/Response	CIViC A	EID12941
ATM Mutation	Olaparib	Sensitivity/Response	CIViC B	EID7458 +2
PTEN Loss	Ipatasertib	Sensitivity/Response	CIViC B	EID10876 +1
AR AR-V7	Galeterone + Enzalutamide	Sensitivity/Response	CIViC B	EID9549
BRCA1 Mutation OR BRCA2 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID11666
BRCA2 Loss-of-function	Olaparib	Sensitivity/Response	CIViC B	EID650
CDK12 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID7473
DEFA1 EXPRESSION	Docetaxel	Sensitivity/Response	CIViC B	EID808
MRE11 Frameshift	Olaparib	Sensitivity/Response	CIViC B	EID1016
PALB2 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID7474
PTEN Deletion	Everolimus	Sensitivity/Response	CIViC B	EID1231
TSPYL1 P62S	Prednisone + Abiraterone	Sensitivity/Response	CIViC B	EID5861
AR AR-V7	Abiraterone + Enzalutamide	Resistance	CIViC B	EID12463 +5
AR AR-V7	Enzalutamide + Abiraterone	Resistance	CIViC B	EID12464 +1
AR AR alternative transcripts	Abiraterone + Enzalutamide	Resistance	CIViC B	EID9578
AR AR-V7	Cabazitaxel	Resistance	CIViC B	EID9552
AR AR-V7	Enzalutamide	Resistance	CIViC B	EID9554
AR Mutation	Flutamide + Cyproterone Acetate + Nilutamide + Bicalutamide	Resistance	CIViC B	EID1521
AR Overexpression of AR-V9	Abiraterone	Resistance	CIViC B	EID9491
AR V567es expression	Taxane Compound	Resistance	CIViC B	EID9579
AKT2 L78_Q79ins	Capivasertib	Sensitivity/Response	CIViC C	EID10763
ATM N2875H	Olaparib	Sensitivity/Response	CIViC C	EID648
ATM S2289*	Olaparib	Sensitivity/Response	CIViC C	EID647
BRCA1 Loss-of-function	Olaparib	Sensitivity/Response	CIViC C	EID845
FANCA S1088F	Cisplatin	Sensitivity/Response	CIViC C	EID5813
PALB2 Biallelic Inactivation	Olaparib	Sensitivity/Response	CIViC C	EID1963
TYMS Underexpression	Pemetrexed	Sensitivity/Response	CIViC C	EID908
IRS2 Amplification	Capivasertib	Resistance	CIViC C	EID10764

+19 more predictive associations (showing top 30 by evidence level).