Prostate cancer

Summary

Prostate cancer (MONDO:0008315) is a cancer (an umbrella term covering 5 Mondo subtypes) caused by HOXB13 (GenCC Definitive), with 60 cohort genes (1,174 GWAS associations across 35 studies; 19 CIViC-evidence somatic drivers; 1,063 ClinVar predisposition records) and 5,734 clinical trials. The dominant Reactome pathway is Defective homologous recombination repair (HRR) due to PALB2 loss of function (5 cohort genes). Molecularly, BRCA1 Mutation confers sensitivity to Olaparib in Prostate Cancer (CIViC Level A); 47 further subtype–drug associations are mapped below. Top therapeutic interventions include leuprolide, goserelin, and bicalutamide.

At a glance

• Classification: Cancer
• Causal gene: HOXB13 (GenCC Definitive)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 60
• GWAS associations: 1,174
• ClinVar variants: 1,063
• Clinical trials: 5,734
• Precision-medicine evidence (CIViC): 48 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prostate cancer
Mondo ID	MONDO:0008315
MeSH	D011471
DOID	DOID:10283
ICD-10-CM	C61
NCIT	C7378
SNOMED CT	399068003
UMLS	C0376358
MedGen	138169
Anatomy (UBERON)	UBERON:0002367
Is cancer (heuristic)	yes

Also known as: cancer of prostate gland · hereditary prostate cancer · malignant neoplasm of prostate · malignant neoplasm of prostate gland · malignant neoplasm of the prostate · malignant prostate gland neoplasm · malignant prostate neoplasm · malignant prostate tumor · malignant prostate tumour · malignant tumor of prostate · malignant tumor of the prostate · malignant tumour of prostate · malignant tumour of the prostate · prostate cancer, familial · prostate gland cancer · prostate neoplasm · prostatic neoplasm · tumor of the prostate · tumour of the prostate

Data availability: 1,063 ClinVar variants · 1,174 GWAS associations (35 studies) · 14 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › reproductive system cancer › male reproductive organ cancer › prostate cancer

Related subtypes (6): epididymis cancer, penile cancer, spermatic cord cancer, carcinoma of Cowper glands, testicular cancer, scrotum cancer

Subtypes (5): malignant prostate phyllodes tumor, prostate lymphoma, prostate sarcoma, prostate carcinoma, prostate cancer, hereditary

Genetics & variants

GWAS landscape

1,174 GWAS associations across 35 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr8:128532399	1e-129		A	0.34
rs4582524	3e-128	CASC8 - CASC11	G	0.34
rs72725854	7e-97	PCAT1	A	0.82
rs12417087	1e-95	SMIM38 - MYEOV	A	0.23
chr11:68981359	4e-93		A	0.23
rs138213197	1e-84	HOXB13	C	1.43
chr17:69109773	4e-64		G	0.15
rs62113212	8e-58	KLK3	C	0.3
chr8:23531987	2e-51		A	0.13
rs995433	1e-50	SINHCAFP3 - NKX3-1	T	0.13
rs8071558	4e-50	CASC17	C	0.13
rs58235267	4e-45	OTX1	C	0.12
rs77541621	2e-44	PCAT1	A	0.59
rs6983267	1e-43	PCAT1, CASC8, POU5F1B, CCAT2	T	0.23
rs5759167	7e-43	RPS25P10 - BIK	G	0.12
rs13255059	9e-43	CASC8 - CASC11	G	1.87
rs1456315	4e-42	PCAT1, CASC19, PRNCR1	C	1.79
rs2242652	7e-41	TERT	G	0.16
rs188140481	4e-40	PCAT1, CASC19	A	1.04
rs78416326	1e-38	PRKCI - SKIL	G	0.15
chr7:27975919	1e-38		G	0.14
rs138042437	1e-37	CASC19, PCAT1	G	1.01
rs2002731	2e-37	HNF1B	T	0.14
rs4919743	9e-36	KRT8	G	0.17
chr11:2224664	1e-35		G	0.14
chr12:53312612	2e-35		C	0.17
rs10908278	5e-35	HNF1B	A	0.21
rs10007915	1e-34	RNU6-351P - TET2	C	0.11
rs10486567	1e-34	JAZF1	G	0.12
rs11651052	4e-34	HNF1B	G	0.21

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90042670	Jiang L	2021	30,487	363,771	A generalized linear mixed model association tool for biobank-scale data.
GCST90475185	Verma A	2024	28,645	264,556	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90428117	Harris BHL	2024	7,822	144,172	New role of fat-free mass in cancer risk linked with genetic predisposition.
GCST90043894	Jiang L	2021	7,769	201,039	A generalized linear mixed model association tool for biobank-scale data.
GCST90475187	Verma A	2024	7,566	285,635	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90042696	Jiang L	2021	5,873	350,300	A generalized linear mixed model association tool for biobank-scale data.
GCST90475184	Verma A	2024	5,764	42,247	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479536	Verma A	2024	5,764	42,247	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90702471	Dias JA	2025	5,323	137,363	Evaluating multi-ancestry genome-wide association methods: Statistical power, population structure, and practical implications.
GCST90503487	Cheng Y	2024	4,882	162,635	An early-onset specific polygenic risk score optimizes age-based risk estimate and stratification of prostate cancer: population-based cohort study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	2
Tier 3: regulatory	3
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	43
low_freq (0.01-0.05)	2
rare (<0.01)	1
unknown	4

Functional consequences

Consequence	Count
intron_variant	23
unknown	14
intergenic_variant	4
non_coding_transcript_exon_variant	3
regulatory_region_variant	2
missense_variant	1
TF_binding_site_variant	1
splice_donor_region_variant	1
splice_donor_5th_base_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr8:128532399				0.113			1e-129	Tier 4: intronic/intergenic
rs4582524	8	127516190	G>A,C	0.107	intergenic_variant	CASC8 - CASC11	3e-128	Tier 4: intronic/intergenic
rs72725854	8	127062570	A>G,T	0.067	intron_variant	PCAT1	7e-97	Tier 4: intronic/intergenic
rs12417087	11	69236512	A>T	0.165	intron_variant	SMIM38 - MYEOV	1e-95	Tier 4: intronic/intergenic
chr11:68981359				0.169			4e-93	Tier 4: intronic/intergenic
rs138213197	17	48728343	C>T	0.002	missense_variant	HOXB13	1e-84	Tier 1: coding
chr17:69109773				0.492			4e-64	Tier 4: intronic/intergenic
rs62113212	19	50857584	C>G,T	0.074	intron_variant	KLK3	8e-58	Tier 4: intronic/intergenic
chr8:23531987				0.438			2e-51	Tier 4: intronic/intergenic
rs995433	8	23665228	T>A,C,G	0.472	intron_variant	SINHCAFP3 - NKX3-1	1e-50	Tier 4: intronic/intergenic
rs8071558	17	71111532	C>G,T	0.454	intron_variant	CASC17	4e-50	Tier 4: intronic/intergenic
rs58235267	2	63050708	C>A,G,T	0.47	regulatory_region_variant	OTX1	4e-45	Tier 3: regulatory
rs77541621	8	127064901	G>A	0.05	intron_variant	PCAT1	2e-44	Tier 4: intronic/intergenic
rs6983267	8	127401060	G>T	0.05	non_coding_transcript_exon_variant	PCAT1, CASC8, POU5F1B, CCAT2	1e-43	Tier 4: intronic/intergenic
rs5759167	22	43104206	G>A,T	0.498	TF_binding_site_variant	RPS25P10 - BIK	7e-43	Tier 3: regulatory
rs13255059	8	127518371	A>G,T	0.126	intergenic_variant	CASC8 - CASC11	9e-43	Tier 4: intronic/intergenic
rs1456315	8	127091692	T>A,C,G	0.282	non_coding_transcript_exon_variant	PCAT1, CASC19, PRNCR1	4e-42	Tier 4: intronic/intergenic
rs2242652	5	1279913	G>A	0.19	intron_variant	TERT	7e-41	Tier 4: intronic/intergenic
rs188140481	8	127179427	T>A,C		intron_variant	PCAT1, CASC19	4e-40	Tier 4: intronic/intergenic
rs78416326	3	170356729	G>C	0.196	non_coding_transcript_exon_variant	PRKCI - SKIL	1e-38	Tier 4: intronic/intergenic
chr7:27975919				0.228			1e-38	Tier 4: intronic/intergenic
rs138042437	8	127196124	A>G		intron_variant	CASC19, PCAT1	1e-37	Tier 4: intronic/intergenic
rs2002731	17	37728539	T>C	0.392	intron_variant	HNF1B	2e-37	Tier 4: intronic/intergenic
rs4919743	12	52915800	G>A	0.119	intron_variant	KRT8	9e-36	Tier 4: intronic/intergenic
chr11:2224664				0.17			1e-35	Tier 4: intronic/intergenic
chr12:53312612				0.117			2e-35	Tier 4: intronic/intergenic
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	5e-35	Tier 4: intronic/intergenic
rs10007915	4	105144151	C>A,G,T	0.396	intron_variant	RNU6-351P - TET2	1e-34	Tier 4: intronic/intergenic
rs10486567	7	27936944	G>A,C	0.249	intron_variant	JAZF1	1e-34	Tier 4: intronic/intergenic
rs11651052	17	37742390	G>A,C,T	0.05	intron_variant	HNF1B	4e-34	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

422 uncertain significance, 66 conflicting classifications of pathogenicity, 37 pathogenic, 23 benign, 19 pathogenic/likely pathogenic, 18 likely benign, 11 benign/likely benign, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685531	NM_000044.6(AR):c.208C>T (p.Gln70Ter)	AR	Pathogenic	criteria provided, single submitter
1685535	NM_000044.6(AR):c.1195T>C (p.Trp399Arg)	AR	Pathogenic	criteria provided, single submitter
1685537	NM_000044.6(AR):c.1208C>T (p.Ala403Val)	AR	Pathogenic	criteria provided, single submitter
1685540	NM_000044.6(AR):c.2184C>G (p.Asn728Lys)	AR	Pathogenic	criteria provided, single submitter
1180448	NM_000059.4(BRCA2):c.643del (p.Glu215fs)	BRCA2	Pathogenic	criteria provided, single submitter
126037	NM_000059.4(BRCA2):c.4131_4132insTGAGGA (p.Thr1378Ter)	BRCA2	Pathogenic	reviewed by expert panel
141283	NM_000059.4(BRCA2):c.1909+1G>A	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141509	NM_000059.4(BRCA2):c.6816_6820del (p.Gly2274fs)	BRCA2	Pathogenic	reviewed by expert panel
1456139	NM_000059.4(BRCA2):c.4793_4794del (p.Leu1598fs)	BRCA2	Pathogenic	criteria provided, multiple submitters, no conflicts
187127	NM_000059.4(BRCA2):c.4914dup (p.Val1639fs)	BRCA2	Pathogenic	reviewed by expert panel
132709	NM_004360.5(CDH1):c.715G>A (p.Gly239Arg)	CDH1	Pathogenic	reviewed by expert panel
136055	NM_004360.5(CDH1):c.1003C>T (p.Arg335Ter)	CDH1	Pathogenic	reviewed by expert panel
140781	NM_004360.5(CDH1):c.2064_2065del (p.Cys688_Glu689delinsTer)	CDH1	Pathogenic	reviewed by expert panel
142888	NM_004360.5(CDH1):c.1147C>T (p.Gln383Ter)	CDH1	Pathogenic	reviewed by expert panel
1066705	NM_007194.4(CHEK2):c.684-2A>G	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128042	NM_007194.4(CHEK2):c.1100del (p.Thr367fs)	CHEK2	Pathogenic	criteria provided, multiple submitters, no conflicts
128053	NM_007194.4(CHEK2):c.1263del (p.Ser422fs)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128075	NM_007194.4(CHEK2):c.444+1G>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
140772	NM_007194.4(CHEK2):c.283C>T (p.Arg95Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141381	NM_007194.4(CHEK2):c.216T>G (p.Tyr72Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141818	NM_007194.4(CHEK2):c.1169A>C (p.Tyr390Ser)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142114	NM_007194.4(CHEK2):c.591del (p.Val198fs)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142352	NM_007194.4(CHEK2):c.319+2T>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142956	NM_007194.4(CHEK2):c.592+3A>T	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182430	NM_007194.4(CHEK2):c.793-1G>A	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182452	NM_007194.4(CHEK2):c.409C>T (p.Arg137Ter)	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216003	NM_007194.4(CHEK2):c.593-1G>T	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
161467	NM_000435.3(NOTCH3):c.146G>T (p.Cys49Phe)	NOTCH3	Pathogenic	criteria provided, single submitter
13657	NM_006218.4(PIK3CA):c.1636C>A (p.Gln546Lys)	PIK3CA	Pathogenic	criteria provided, multiple submitters, no conflicts
190430	NM_016218.6(POLK):c.*66T>C	POLK	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 53 · Orphanet: 111 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
HOXB13			CIViC #8351
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
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
CHEK2	Act	BRCA	CIViC #8950
MRE11			CIViC #3586
MSH6			CIViC #2478
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
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
SPOP	Act	NHL,PRAD,PROSTATE,UCEC,UCS	CIViC #6652
TF			CIViC #5723
TGFBR3			CIViC #5752
TMPRSS2	Act	PRAD	CIViC #5813
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
TRRAP	Act	ACYC,ANGS,BLCA,CCRCC,CHOL,HNSC,LMS,LUAD,MEL
KDM6A	LoF	ALL,BLADDER,BLCA,BRCA,ESCA,ESCC,GBC,HCC,HNSC,LUSC,MBL,PAAD,PAST,PRAD,PRCC,PROSTATE,SCLC,STAD	CIViC #6054

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
HOXB13	Definitive	Autosomal dominant	prostate cancer	2
ATM	Moderate	Autosomal dominant	prostate cancer	14
BIK	Limited	Autosomal dominant	prostate cancer
MSH6	Limited	Autosomal dominant	prostate cancer	17
NBN	Limited	Autosomal dominant	prostate cancer	8
RAPGEF4	Limited	Autosomal dominant	prostate cancer
ULK4	Limited	Autosomal dominant	prostate cancer
XPO7	Limited	Autosomal dominant	prostate cancer
MRE11	Disputed Evidence	Autosomal dominant	prostate cancer	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HOXB13	Orphanet:1331	Familial prostate cancer
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
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
MRE11	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
MRE11	Orphanet:240760	Nijmegen breakage syndrome-like disorder
MRE11	Orphanet:251347	Ataxia-telangiectasia-like disorder
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
NBN	Orphanet:1331	Familial prostate cancer
NBN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
NBN	Orphanet:647	Nijmegen breakage syndrome
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx

Cohort genes → proteins

60 cohort genes, 60 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	4
multi_evidence	56

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HOXB13	HGNC:5112	ENSG00000159184	Q92826	Homeobox protein Hox-B13	gencc,clinvar,civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	gencc,clinvar,civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar,civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar,civic_evidence
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar,civic_evidence
MRE11	HGNC:7230	ENSG00000020922	P49959	Double-strand break repair protein MRE11	gencc,civic_evidence
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	gencc,clinvar
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	gencc,clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar,civic_evidence
BIK	HGNC:1051	ENSG00000100290	Q13323	Bcl-2-interacting killer	gencc
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	civic_evidence
TYMS	HGNC:12441	ENSG00000176890	P04818	Thymidylate synthase	civic_evidence
XPO7	HGNC:14108	ENSG00000130227	Q9UIA9	Exportin-7	gencc
ULK4	HGNC:15784	ENSG00000168038	Q96C45	Serine/threonine-protein kinase ULK4	gencc
RAPGEF4	HGNC:16626	ENSG00000091428	Q8WZA2	Rap guanine nucleotide exchange factor 4	gencc
CFLAR	HGNC:1876	ENSG00000003402	O15519	CASP8 and FADD-like apoptosis regulator	civic_evidence
CDK12	HGNC:24224	ENSG00000167258	Q9NYV4	Cyclin-dependent kinase 12	civic_evidence
RNASEL	HGNC:10050	ENSG00000135828	Q05823	2-5A-dependent ribonuclease	clinvar
RPS6KC1	HGNC:10439	ENSG00000136643	Q96S38	Ribosomal protein S6 kinase delta-1	clinvar
SERPINB4	HGNC:10570	ENSG00000206073	P48594	Serpin B4	clinvar
SCNN1A	HGNC:10599	ENSG00000111319	P37088	Epithelial sodium channel subunit alpha	clinvar
NEMF	HGNC:10663	ENSG00000165525	O60524	Ribosome quality control complex subunit NEMF	clinvar
SEZ6L	HGNC:10763	ENSG00000100095	Q9BYH1	Seizure 6-like protein	clinvar
SF3B3	HGNC:10770	ENSG00000189091	Q15393	Splicing factor 3B subunit 3	clinvar
SI	HGNC:10856	ENSG00000090402	P14410	Sucrase-isomaltase, intestinal	clinvar
SIGLEC6	HGNC:10875	ENSG00000105492	O43699	Sialic acid-binding Ig-like lectin 6	clinvar
SKIL	HGNC:10897	ENSG00000136603	P12757	Ski-like protein	clinvar
SLC16A2	HGNC:10923	ENSG00000147100	P36021	Monocarboxylate transporter 8	clinvar
SLC30A2	HGNC:11013	ENSG00000158014	Q9BRI3	Proton-coupled zinc antiporter SLC30A2	clinvar
SLC34A1	HGNC:11019	ENSG00000131183	Q06495	Sodium-dependent phosphate transport protein 2A	clinvar
SLC5A2	HGNC:11037	ENSG00000140675	P31639	Sodium/glucose cotransporter 2	clinvar
SLC6A9	HGNC:11056	ENSG00000196517	P48067	Sodium- and chloride-dependent glycine transporter 1	clinvar
BABAM2	HGNC:1106	ENSG00000158019	Q9NXR7	BRISC and BRCA1-A complex member 2	clinvar
SLC8A3	HGNC:11070	ENSG00000100678	P57103	Sodium/calcium exchanger 3	clinvar
ZFP36L2	HGNC:1108	ENSG00000152518	P47974	mRNA decay activator protein ZFP36L2	clinvar
SMARCC2	HGNC:11105	ENSG00000139613	Q8TAQ2	SWI/SNF complex subunit SMARCC2	clinvar
SPOP	HGNC:11254	ENSG00000121067	O43791	Speckle-type POZ protein	clinvar
STX8	HGNC:11443	ENSG00000170310	Q9UNK0	Syntaxin-8	clinvar
STXBP1	HGNC:11444	ENSG00000136854	P61764	Syntaxin-binding protein 1	clinvar
SYCP2	HGNC:11490	ENSG00000196074	Q9BX26	Synaptonemal complex protein 2	clinvar
SYNGR1	HGNC:11498	ENSG00000100321	O43759	Synaptogyrin-1	clinvar
TEX14	HGNC:11737	ENSG00000121101	Q8IWB6	Inactive serine/threonine-protein kinase TEX14	clinvar
TF	HGNC:11740	ENSG00000091513	P02787	Serotransferrin	clinvar
TG	HGNC:11764	ENSG00000042832	P01266	Thyroglobulin	clinvar
TGFBR3	HGNC:11774	ENSG00000069702	Q03167	Transforming growth factor beta receptor type 3	clinvar
MYRF	HGNC:1181	ENSG00000124920	Q9Y2G1	Myelin regulatory factor	clinvar
TMPRSS2	HGNC:11876	ENSG00000184012	O15393	Transmembrane protease serine 2	clinvar
MRPL46	HGNC:1192	ENSG00000259494	Q9H2W6	Large ribosomal subunit protein mL46	clinvar
TNFRSF8	HGNC:11923	ENSG00000120949	P28908	Tumor necrosis factor receptor superfamily member 8	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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.
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.
MRE11	Double-strand break repair protein MRE11	Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
NBN	Nibrin	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
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.
BIK	Bcl-2-interacting killer	Accelerates programmed cell death.
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…
XPO7	Exportin-7	Mediates the nuclear export of proteins (cargos) with broad substrate specificity.
ULK4	Serine/threonine-protein kinase ULK4	May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.
RAPGEF4	Rap guanine nucleotide exchange factor 4	Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP.
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.
RNASEL	2-5A-dependent ribonuclease	Endoribonuclease that functions in the interferon (IFN) antiviral response.
RPS6KC1	Ribosomal protein S6 kinase delta-1	May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell.
SERPINB4	Serpin B4	May act as a protease inhibitor to modulate the host immune response against tumor cells.
SCNN1A	Epithelial sodium channel subunit alpha	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
NEMF	Ribosome quality control complex subunit NEMF	Key component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes as well as their ubiquitin-mediated proteasomal degra…
SEZ6L	Seizure 6-like protein	May contribute to specialized endoplasmic reticulum functions in neurons.
SF3B3	Splicing factor 3B subunit 3	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
SI	Sucrase-isomaltase, intestinal	Plays an important role in the final stage of carbohydrate digestion.
SIGLEC6	Sialic acid-binding Ig-like lectin 6	Putative adhesion molecule that mediates sialic-acid dependent binding to cells.
SKIL	Ski-like protein	May have regulatory role in cell division or differentiation in response to extracellular signals.
SLC16A2	Monocarboxylate transporter 8	Specific thyroid hormone transmembrane transporter, that mediates both uptake and efflux of thyroid hormones across the cell membrane independently of pH or a Na(+) gradient.
SLC30A2	Proton-coupled zinc antiporter SLC30A2	Electroneutral proton-coupled antiporter concentrating zinc ions into a variety of intracellular organelles including endosomes, zymogen granules and mitochondria.
SLC34A1	Sodium-dependent phosphate transport protein 2A	Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.
SLC5A2	Sodium/glucose cotransporter 2	Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1.
SLC6A9	Sodium- and chloride-dependent glycine transporter 1	Sodium- and chloride-dependent glycine transporter.
BABAM2	BRISC and BRCA1-A complex member 2	Component of the BRCA1-A complex, a complex that specifically recognizes ‘Lys-63’-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks…
SLC8A3	Sodium/calcium exchanger 3	Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes.
ZFP36L2	mRNA decay activator protein ZFP36L2	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…
SMARCC2	SWI/SNF complex subunit SMARCC2	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
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.
STX8	Syntaxin-8	Vesicle trafficking protein that functions in the early secretory pathway, possibly by mediating retrograde transport from cis-Golgi membranes to the ER.
STXBP1	Syntaxin-binding protein 1	Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins.
SYCP2	Synaptonemal complex protein 2	Major component of the axial/lateral elements of synaptonemal complexes (SCS) during meiotic prophase.
SYNGR1	Synaptogyrin-1	May play a role in regulated exocytosis.
TEX14	Inactive serine/threonine-protein kinase TEX14	Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis.
TF	Serotransferrin	Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.
TG	Thyroglobulin	Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3).
TGFBR3	Transforming growth factor beta receptor type 3	Cell surface receptor that regulates diverse cellular processes including cell proliferation, differentiation, migration, and apoptosis.
MYRF	Myelin regulatory factor	Constitutes a precursor of the transcription factor.
TMPRSS2	Transmembrane protease serine 2	Plasma membrane-anchored serine protease that cleaves at arginine residues.
TNFRSF8	Tumor necrosis factor receptor superfamily member 8	Receptor for TNFSF8/CD30L.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TRIP12	E3 ubiquitin-protein ligase TRIP12	E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair.

Protein-family classification

Druggable: 24 · Difficult: 8 · Unknown: 28 · Druggable fraction: 0.4

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	9	4.2×	0.003
Ion channel	2	3.7×	0.556
Complement	1	4.5×	0.735
Antibody/Immunoglobulin	3	1.5×	0.735
Phosphatase	1	1.4×	0.735
Transporter	1	1.3×	0.735
Protease	2	1.2×	0.735
Enzyme (other)	5	1.0×	0.735
Transcription factor	7	1.0×	0.735
Other/Unknown	28	0.8×	0.972
Scaffold/PPI	1	0.3×	0.972

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HOXB13	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
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
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
MRE11	Other/Unknown	no		Mre11, Calcineurin-like_PHP, Mre11_DNA-bd
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
BIK	Other/Unknown	no		Bcl2_BH3_motif_CS, Bcl2-int_killer
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
XPO7	Other/Unknown	no		Importin-beta_N, ARM-like, ARM-type_fold
ULK4	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, ARM-like
RAPGEF4	Other/Unknown	no		DEP_dom, cNMP-bd_dom, Ras-like_Gua-exchang_fac_N
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
RNASEL	Kinase	yes	4.6.1.19	Prot_kinase_dom, Ankyrin_rpt, KEN_dom
RPS6KC1	Kinase	yes		Prot_kinase_dom, PX_dom, MIT_dom
SERPINB4	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom
SCNN1A	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
NEMF	Other/Unknown	no		NFACT_RNA-bd, NFACT-C, RQC_Subunit_NEMF
SEZ6L	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
SF3B3	Scaffold/PPI	no		RSE1/DDB1/CPSF1_C, WD40/YVTN_repeat-like_dom_sf, Beta-prop_RSE1/DDB1/CPSF1_1st
SI	Enzyme (other)	yes	3.2.1.10	Glyco_hydro_31_TIM, P_trefoil_dom, Gal_mutarotase_sf_dom
SIGLEC6	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_sub2, Ig_sub
SKIL	Other/Unknown	no		SKI/SNO/DAC, DNA-bd_dom_put_sf, SAND-like_dom_sf
SLC16A2	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
SLC30A2	Other/Unknown	no		Cation_efflux, Cation_efflux_TMD_sf, Cation_efflux_CTD
SLC34A1	Other/Unknown	no		Na/Pi_transpt
SLC5A2	Other/Unknown	no		Na/solute_symporter, Na/solute_symporter_CS, Na/Glc_symporter_sf
SLC6A9	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_glycine_GLY1, SNS_sf
BABAM2	Other/Unknown	no		BRE
SLC8A3	Other/Unknown	no		Calx_beta, Na_Ca_Ex, NaCa_Exmemb
ZFP36L2	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf
SMARCC2	Transcription factor	no		Chromo/chromo_shadow_dom, SANT/Myb, SWIRM
SPOP	Other/Unknown	no		BTB/POZ_dom, MATH/TRAF_dom, TRAF-like
STX8	Other/Unknown	no		T_SNARE_dom, Syntaxin-8_SNARE, Syntaxin
STXBP1	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
SYCP2	Other/Unknown	no		SYCP2-like, SYCP2_SLD, SYCP2_ARLD
SYNGR1	Other/Unknown	no		Marvel, Synaptogyrin
TEX14	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ankyrin_rpt
TF	Other/Unknown	no		Transferrin-like_dom, Transferrin, Transferrin_Fe_BS
TG	Other/Unknown	no		Thyroglobulin_1, CarbesteraseB, Tyr-kin_ephrin_A/B_rcpt-like
TGFBR3	Other/Unknown	no		ZP_dom, ZP_dom_CS, ZP-C_dom
MYRF	Transcription factor	no		p53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2
TMPRSS2	Protease	yes	3.4.21.B60	SRCR, Trypsin_dom, Peptidase_S1A
MRPL46	Other/Unknown	no		NUDIX_hydrolase-like_dom_sf, Ribosomal_mL46_N, Ribosomal_mL46_NUDIX
TNFRSF8	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_8, TNFRSF8_N
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn

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)	60
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	8
calcaneal tendon	7
male germ line stem cell (sensu Vertebrata) in testis	6
ganglionic eminence	6
secondary oocyte	5
buccal mucosa cell	5
sperm	4
left testis	4
right testis	4
corpus callosum	3
primordial germ cell in gonad	3
oocyte	3
nasal cavity epithelium	3
apex of heart	3
cortical plate	3
mucosa of sigmoid colon	2
embryo	2
mammary duct	2
endothelial cell	2
palpebral conjunctiva	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HOXB13	38	broad	marker	rectum, mucosa of sigmoid colon, prostate gland
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
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
MRE11	254	ubiquitous	marker	calcaneal tendon, oocyte, secondary oocyte
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
NBN	299	ubiquitous	marker	endometrium epithelium, mammary duct, cauda epididymis
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
BIK	192	broad	marker	nasal cavity epithelium, olfactory segment of nasal mucosa, palpebral conjunctiva
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
TYMS	262	ubiquitous	marker	ventricular zone, embryo, trabecular bone tissue
XPO7	295	ubiquitous	marker	trabecular bone tissue, middle frontal gyrus, Brodmann (1909) area 10
ULK4	203	ubiquitous	marker	decidua, secondary oocyte, buccal mucosa cell
RAPGEF4	244	broad	marker	right frontal lobe, amygdala, dorsolateral prefrontal cortex
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
RNASEL	249	ubiquitous	marker	amniotic fluid, palpebral conjunctiva, germinal epithelium of ovary
RPS6KC1	275	ubiquitous	marker	sperm, male germ cell, calcaneal tendon
SERPINB4	140	tissue_specific	marker	nasal cavity epithelium, mammalian vulva, cervix squamous epithelium
SCNN1A	283	broad	marker	nasal cavity epithelium, metanephros cortex, right uterine tube
NEMF	292	ubiquitous	marker	calcaneal tendon, tendon, medial globus pallidus
SEZ6L	167	broad	marker	ganglionic eminence, endothelial cell, lateral nuclear group of thalamus
SF3B3	296	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
SI	66	tissue_specific	marker	jejunal mucosa, ileal mucosa, ileum
SIGLEC6	131	tissue_specific	marker	buccal mucosa cell, placenta, tibialis anterior
SKIL	280	ubiquitous	marker	tendon of biceps brachii, mucosa of paranasal sinus, tendon
SLC16A2	183	ubiquitous	marker	right adrenal gland, right adrenal gland cortex, right lobe of liver
SLC30A2	115	tissue_specific	marker	kidney epithelium, body of pancreas, epithelial cell of pancreas
SLC34A1	52	tissue_specific	marker	nephron tubule, adult mammalian kidney, kidney epithelium

Protein interactions among cohort

Intra-cohort edges: 57.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
PTEN	11,626
BRCA1	9,064
KDM6A	8,825
ATM	7,383
RNASEL	6,889
SPOP	5,899
STK11	5,146
TRRAP	4,847
BRCA2	4,839

Intra-cohort edges

A	B	Sources
ATM	BABAM2	string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CDK12	string_interaction
ATM	CHEK2	string_interaction
ATM	MRE11	string_interaction
ATM	MSH6	string_interaction
ATM	NBN	biogrid_interaction, string_interaction
ATM	STK11	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BABAM2	BRCA1	biogrid_interaction, intact, string_interaction
BABAM2	BRCA2	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	CDK12	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	HOXB13	string_interaction
BRCA1	MRE11	string_interaction
BRCA1	MSH6	string_interaction
BRCA1	NBN	string_interaction
BRCA1	TP53	string_interaction
BRCA1	USF2	biogrid_interaction, string_interaction
BRCA1	USP28	intact
BRCA2	CDK12	string_interaction
BRCA2	CHEK2	string_interaction
BRCA2	HOXB13	string_interaction
BRCA2	MRE11	string_interaction
BRCA2	MSH6	string_interaction
BRCA2	NBN	string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
CFLAR	SF3B3	biogrid_interaction
CHEK2	MRE11	string_interaction
CHEK2	MSH6	string_interaction
CHEK2	NBN	string_interaction
CHEK2	SF3B3	intact
CHEK2	TP53	intact, string_interaction
CHEK2	USP28	string_interaction
KDM6A	MSH6	biogrid_interaction
KDM6A	PTEN	biogrid_interaction
MRE11	NBN	intact, string_interaction
MSH6	NBN	string_interaction
PTEN	SPOP	string_interaction
PTEN	STK11	string_interaction
PTEN	TP53	string_interaction
RNASEL	TP53	intact
SERPINB4	USF2	biogrid_interaction
SF3B3	TRRAP	intact
SI	SLC5A2	string_interaction
SLC16A2	SLC30A2	biogrid_interaction
SLC16A2	SYNGR1	biogrid_interaction

Structural data

PDB: 47 · AlphaFold-only: 13 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
MRPL46	Q9H2W6	82
SF3B3	Q15393	67
TF	P02787	66
TYMS	P04818	61
CDK12	Q9NYV4	39
CHEK2	O96017	38
SPOP	O43791	36
TMPRSS2	O15393	34
BRCA1	P38398	33
CFLAR	O15519	17
USP28	Q96RU2	15
ATM	Q13315	14
BRCA2	P51587	14
PTEN	P60484	12
SLC5A2	P31639	12
HOXB13	Q92826	10
MRE11	P49959	10
SLC6A9	P48067	9
SMARCC2	Q8TAQ2	9
TRRAP	Q9Y4A5	9
MSH6	P52701	8
NBN	O60934	7
SLC16A2	P36021	7
RNASEL	Q05823	5
TRIP12	Q14669	5
KDM6A	O15550	5
STK11	Q15831	4
BABAM2	Q9NXR7	4
TRPC1	P48995	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SERPINB4	P48594	89.67
XPO7	Q9UIA9	87.45
RAPGEF4	Q8WZA2	87.41
SLC30A2	Q9BRI3	77.86
SIGLEC6	O43699	77.55
SLC8A3	P57103	76.87
STX8	Q9UNK0	76.58
SLC34A1	Q06495	72.24
UMODL1	Q5DID0	69.69
BIK	Q13323	62.38
RPS6KC1	Q96S38	56.74
SYCP2	Q9BX26	54.36
USH2A	O75445

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 747. Enrichment computed across 249 evidence-associated genes (165 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 165 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective homologous recombination repair (HRR) due to PALB2 loss of function	5	28.8×	2e-04	ATM, BRCA1, BRCA2, MRE11, NBN
Diseases of DNA repair	6	20.8×	2e-04	ATM, BRCA1, BRCA2, MRE11, MSH6, NBN
Diseases of DNA Double-Strand Break Repair	5	24.7×	2e-04	ATM, BRCA1, BRCA2, MRE11, NBN
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	5	24.7×	2e-04	ATM, BRCA1, BRCA2, MRE11, NBN
Resolution of D-Loop Structures	5	19.2×	7e-04	ATM, BRCA1, BRCA2, MRE11, NBN
Homology Directed Repair	6	11.2×	0.001	ATM, BRCA1, BRCA2, MRE11, NBN, BABAM2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	6	11.2×	0.001	ATM, BRCA1, BRCA2, MRE11, NBN, BABAM2
DNA Double Strand Break Response	5	14.4×	0.002	ATM, BRCA1, MRE11, NBN, BABAM2
Meiosis	6	10.4×	0.002	ATM, BRCA1, BRCA2, MRE11, NBN, SYCP2
Impaired BRCA2 binding to PALB2	5	13.8×	0.002	ATM, BRCA1, BRCA2, MRE11, NBN
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	5	12.8×	0.002	ATM, BRCA1, BRCA2, MRE11, NBN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	5	12.8×	0.002	ATM, BRCA1, BRCA2, MRE11, NBN
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	5	12.8×	0.002	ATM, BRCA1, BRCA2, MRE11, NBN
Stabilization of p53	4	18.5×	0.002	ATM, CHEK2, TP53, ADRM1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	5	11.9×	0.002	ATM, BRCA1, BRCA2, MRE11, NBN
DNA Double-Strand Break Repair	6	9.0×	0.002	ATM, BRCA1, BRCA2, MRE11, NBN, BABAM2
Sensing of DNA Double Strand Breaks	3	34.6×	0.003	ATM, MRE11, NBN
Homologous DNA Pairing and Strand Exchange	5	11.5×	0.003	ATM, BRCA1, BRCA2, MRE11, NBN
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	7	6.2×	0.005	ATM, BRCA1, CHEK2, MRE11, NBN, BABAM2, TP53
Impaired BRCA2 binding to RAD51	5	9.3×	0.007	ATM, BRCA1, BRCA2, MRE11, NBN
Resolution of D-loop Structures through Holliday Junction Intermediates	5	9.1×	0.007	ATM, BRCA1, BRCA2, MRE11, NBN
Reproduction	6	6.9×	0.007	ATM, BRCA1, BRCA2, MRE11, NBN, SYCP2
G2/M Checkpoints	7	5.7×	0.007	ATM, BRCA1, MRE11, NBN, BABAM2, TP53, ADRM1
DNA Repair	8	4.8×	0.008	ATM, BRCA1, BRCA2, MRE11, MSH6, NBN, BABAM2, SMUG1
Presynaptic phase of homologous DNA pairing and strand exchange	5	8.2×	0.010	ATM, BRCA1, BRCA2, MRE11, NBN
G2/M DNA damage checkpoint	7	5.1×	0.013	ATM, BRCA1, CHEK2, MRE11, NBN, BABAM2, TP53
Regulation of TP53 Activity through Phosphorylation	7	5.0×	0.014	ATM, BRCA1, CHEK2, MRE11, NBN, STK11, TP53
TP53 Regulates Transcription of Caspase Activators and Caspases	3	17.3×	0.016	ATM, TP53, TP63
HDR through MMEJ (alt-NHEJ)	3	16.0×	0.020	BRCA2, MRE11, NBN
Cell-Cell communication	6	5.0×	0.031	CD2AP, CDH1, CADM3, CDH3, MAGI2, SDK1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 229 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
double-strand break repair	9	8.0×	0.003	ATM, BRCA1, BRCA2, CHEK2, MRE11, NBN, BABAM2, TP53 (+1 more)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	6	13.0×	0.004	BRCA2, CHEK2, TP53, USP28, TP63, TOPORS
mitotic G2 DNA damage checkpoint signaling	6	11.6×	0.005	ATM, BRCA1, MRE11, NBN, BABAM2, TAOK3
DNA damage response	15	3.5×	0.010	ATM, BRCA1, CHEK2, MRE11, BABAM2, STK11, TP53, TRIP12 (+7 more)
intrinsic apoptotic signaling pathway in response to DNA damage	6	8.5×	0.020	ATM, BRCA1, CHEK2, MSH6, SKIL, TOPORS
DNA strand resection involved in replication fork processing	3	27.6×	0.031	BRCA1, MRE11, NBN
mitotic G2/M transition checkpoint	4	14.0×	0.033	BRCA1, MRE11, NBN, BABAM2
response to ionizing radiation	5	9.0×	0.039	ATM, BRCA1, BABAM2, STK11, USP28
DNA double-strand break processing	3	20.1×	0.058	ATM, MRE11, NBN
DNA damage response, signal transduction by p53 class mediator	5	7.8×	0.059	ATM, BRCA2, CHEK2, NBN, TP53
homologous recombination	3	18.4×	0.063	BRCA1, MRE11, NBN
DNA replication-dependent chromatin disassembly	2	49.1×	0.063	KAT7, ING4
double-strand break repair via homologous recombination	7	4.8×	0.073	ATM, BRCA1, BRCA2, MRE11, NBN, FBH1, POLN
negative regulation of intracellular estrogen receptor signaling pathway	3	14.7×	0.087	BRCA1, TP63, CDK12
regulation of DNA damage checkpoint	3	14.7×	0.087	BRCA1, BRCA2, BABAM2
DNA repair	11	3.1×	0.087	BRCA1, MRE11, MSH6, TRIP12, USP28, UVRAG, FBH1, TRIM28 (+3 more)
telomeric 3’ overhang formation	2	36.8×	0.089	MRE11, NBN
collagen biosynthetic process	3	13.8×	0.093	ADAMTS3, COL1A1, COL5A1
homophilic cell-cell adhesion	7	4.3×	0.093	DSCAML1, CDH1, CADM3, CDH3, HMCN1, SDK1, DCHS2
cell migration	11	3.0×	0.094	PTEN, TGFBR3, NTN4, CD2AP, PAK4, CDH1, CDH3, HHIPL1 (+3 more)
replicative senescence	3	13.0×	0.097	ATM, CHEK2, TP53
cellular response to indole-3-methanol	2	29.4×	0.108	BRCA1, CDH1
negative regulation of telomere capping	2	29.4×	0.108	ATM, NBN
determination of adult lifespan	4	7.5×	0.109	ATM, MSH6, TP53, TP63
cell-cell adhesion mediated by cadherin	4	7.2×	0.121	CD2AP, CDH1, CDH3, DCHS2
cellular response to ionizing radiation	4	7.2×	0.121	BRCA1, BRCA2, BABAM2, TP53
regulation of cardiac conduction	3	11.0×	0.123	SLC8A3, TRPC1, CORIN
central nervous system myelin maintenance	2	24.5×	0.127	PTEN, MYRF
calcium ion import	3	10.5×	0.127	TRPC4, CACNA1D, CASK
DNA damage checkpoint signaling	4	6.8×	0.127	ATM, CHEK2, NBN, USP28

Therapeutics

Drugs indicated for this disease

8 approved, 3 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)
Cabazitaxel	Approved (phase 4)
Darolutamide	Approved (phase 4)
Docetaxel Anhydrous	Approved (phase 4)
Enzalutamide	Approved (phase 4)
Nilutamide	Approved (phase 4)
Relugolix	Approved (phase 4)
Abiraterone	Phase 3 (in late-stage trials)
Degarelix	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 15 · Phase ≥3: 16 · Phased (≥1): 19 · Undrugged: 41

Druggability breadth: 88 of 249 evidence-associated genes (35%) 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
ATM	AMIODARONE HYDROCHLORIDE
BRCA1	RIBOFLAVIN
CHEK2	NERATINIB
STK11	FEDRATINIB
TYMS	FOLIC ACID
SCNN1A	AMILORIDE
SF3B3	TACROLIMUS ANHYDROUS
SI	MIGLUSTAT
SLC34A1	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS
SLC5A2	ERTUGLIFLOZIN
SLC6A9	GLYCINE
TMPRSS2	DEBRISOQUIN
TP53	NITROFURANTOIN
USP28	VISMODEGIB
KDM6A	DEFERIPRONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
ATM	35	4
CHEK2	30	4
STK11	17	4
CDK12	17	3
SLC5A2	16	4
BRCA1	12	4
TYMS	9	4
SI	9	4
TMPRSS2	9	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
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, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM, BRCA1
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2, STK11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 13.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
CHEK2	690	Binding:687, Functional:2, ADMET:1
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
SLC5A2	160	Binding:157, Functional:2, ADMET:1
SI	148	Binding:148
SLC6A9	88	Binding:83, Functional:5
SPOP	82	Binding:82
RNASEL	43	Binding:42, Functional:1
SF3B3	41	Binding:41
KDM6A	40	Binding:36, Functional:4
MRE11	36	Binding:36
USP28	32	Binding:32
TMPRSS2	28	Binding:28
RAPGEF4	24	Binding:22, Functional:2
RPS6KC1	22	Binding:22
TF	22	Binding:13, Functional:9
TRPC4	22	Binding:18, ADMET:4
TRPC1	19	Binding:15, ADMET:4
BRCA1	13	Binding:9, Functional:4
MSH6	10	Binding:10
PTEN	8	Binding:8
SLC34A1	8	Binding:7, Functional:1
SMARCC2	7	Binding:7
SCNN1A	6	Binding:4, ADMET:1, Functional:1
CFLAR	4	Binding:4
NBN	2	Binding:2
UVRAG	2	Binding:2
XPO7	1	Binding:1
SLC16A2	1	Functional:1
STXBP1	1	Binding:1
TRRAP	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATM	2.7.11.1	non-specific serine/threonine protein kinase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
CHEK2	2.7.11.1	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
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
RNASEL	4.6.1.19	ribonuclease T2
SI	3.2.1.10, 3.2.1.48	oligo-1,6-glucosidase, sucrose alpha-glucosidase
TMPRSS2	3.4.21.B60
TRIP12	2.3.2.26	HECT-type E3 ubiquitin transferase
KDM6A	1.14.11.68	[histone H3]-trimethyl-L-lysine27 demethylase
UVRAG	2.7.1.137	phosphatidylinositol 3-kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240
CHEK2	690
STK11	244
TYMS	376
CDK12	347
SI	148
SLC5A2	160
TP53	869

Pharmacogenomics

Cohort genes with a PharmGKB record: 60; 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)
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
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, TP53
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM, TP53
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM, BRCA1
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
NERATINIB	4	CHEK2
BOSUTINIB	4	CHEK2
BRIGATINIB	4	CHEK2
SUNITINIB	4	CHEK2, STK11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	15	ATM, BRCA1, CHEK2, STK11, TYMS, SCNN1A, SF3B3, SI, SLC34A1, SLC5A2 (+5 more)
B	Phased (≥1) drug, not yet approved	4	MSH6, CDK12, TRPC1, TRPC4
C	Druggable family + PDB, no drug	9	PTEN, ULK4, RNASEL, SEZ6L, SLC16A2, TEX14, TRIP12, TRRAP, UVRAG
D	Druggable family + AlphaFold only, no drug	4	RPS6KC1, SIGLEC6, UMODL1, USH2A
E	Difficult family or no structure, no drug	28	HOXB13, BRCA2, MRE11, NBN, BIK, XPO7, RAPGEF4, CFLAR, SERPINB4, NEMF (+18 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
MRE11	36	BRCA1, ATM
NBN	2	ATM, BRCA1
PTEN	8	STK11, TP53
USF2	0	BRCA1
HOXB13	0	—
BIK	0	—
XPO7	1	—
ULK4	0	—
RAPGEF4	24	—
CFLAR	4	—
RNASEL	43	—
RPS6KC1	22	—
SERPINB4	0	—
NEMF	0	—
SEZ6L	0	—
SIGLEC6	0	—
SKIL	0	—
SLC16A2	1	—
SLC30A2	0	—
BABAM2	0	—
SLC8A3	0	—
ZFP36L2	0	—
SMARCC2	7	—
SPOP	82	—
STX8	0	—
STXBP1	1	—
SYCP2	0	—
SYNGR1	0	—
TEX14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5,734.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	470
PHASE2	379
PHASE4	108
PHASE1/PHASE2	73
PHASE2/PHASE3	70

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
NCT04108208	PHASE4	ACTIVE_NOT_RECRUITING	A Study of Apalutamide in Chinese Participants With Non Metastatic Castration Resistant Prostate Cancer (NM-CRPC)
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.
NCT06706921	PHASE4	RECRUITING	18F-Fluciclovine PET/CT Impact on Predicting Clinical Outcome of 177Lu-PSMA-617 Therapy in Patients With 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
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
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
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
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LEUPROLIDE	4	120
GOSERELIN	4	119
BICALUTAMIDE	4	56
ZOLEDRONIC ACID ANHYDROUS	4	56
TALAZOPARIB	4	49
DOCETAXEL ANHYDROUS	4	48
ABIRATERONE ACETATE	4	43
DEGARELIX	4	38
ENZALUTAMIDE	4	38
TRIPTORELIN	4	36
FLUTAMIDE	4	33
MITOXANTRONE	4	27
ESTRAMUSTINE PHOSPHATE SODIUM	4	21
ABIRATERONE	4	20
APALUTAMIDE	4	20
GONADORELIN	4	14
KETOCONAZOLE	4	14
LEVOKETOCONAZOLE	4	14
CABAZITAXEL	4	12
IMATINIB	4	12
CALCITRIOL	4	11
DAROLUTAMIDE	4	8
DUTASTERIDE	4	7
GALLIUM GA 68 GOZETOTIDE	4	7
NILUTAMIDE	4	6
PIFLUFOLASTAT F18	4	6
RELUGOLIX	4	6
VINORELBINE TARTRATE	4	6
FLUCICLOVINE F18	4	5
HYDROCORTISONE	4	5

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 48 predictive associations from 61 curated evidence items; also 13 prognostic, 6 predisposing, 4 oncogenic, 4 diagnostic.

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

+18 more predictive associations (showing top 30 by evidence level).