Exocrine pancreatic carcinoma

Summary

Exocrine pancreatic carcinoma (MONDO:0005192) is a cancer (an umbrella term covering 8 Mondo subtypes) with 75 cohort genes (303 GWAS associations across 53 studies; 27 CIViC-evidence somatic drivers; 132 ClinVar predisposition records) and 2,737 clinical trials. The dominant Reactome pathway is Impaired BRCA2 binding to PALB2 (7 cohort genes). Molecularly, BRCA2 Mutation confers sensitivity to Rucaparib in Pancreatic Cancer (CIViC Level B); 54 further subtype–drug associations are mapped below. Top therapeutic interventions include oxaliplatin, gemcitabine, and irinotecan.

At a glance

• Classification: Cancer
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 303
• ClinVar variants: 132
• Clinical trials: 2,737
• Precision-medicine evidence (CIViC): 55 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	exocrine pancreatic carcinoma
Mondo ID	MONDO:0005192
EFO	EFO:0002618
DOID	DOID:4905
NCIT	C3850
SNOMED CT	372142002
UMLS	C0235974
MedGen	65917
GARD	0027717
Anatomy (UBERON)	UBERON:0000017
Is cancer (heuristic)	yes

Also known as: cancer of pancreas · cancer of the pancreas · carcinoma of exocrine pancreas · carcinoma of the pancreas · exocrine cancer · exocrine pancreas carcinoma · pancreas cancer · pancreas carcinoma · pancreatic cancer · pancreatic cancer (not islets) · pancreatic carcinoma, familial

Data availability: 132 ClinVar variants · 303 GWAS associations (53 studies).

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › malignant pancreatic neoplasm › malignant exocrine pancreas neoplasm › exocrine pancreatic carcinoma

Related subtypes (3): pancreatic intraductal papillary-mucinous neoplasm, pancreatoblastoma, solid pseudopapillary neoplasm of the pancreas

Subtypes (8): pancreatic intraductal papillary-mucinous carcinoma, pancreatic adenocarcinoma, pancreatic large cell neuroendocrine carcinoma, familial pancreatic carcinoma, squamous cell carcinoma of pancreas, pancreatic mucinous cystadenoma, solid pseudopapillary carcinoma of pancreas, pancreatic carcinoma with mixed differentiation

Genetics & variants

GWAS landscape

303 GWAS associations across 53 studies. Top hits map to 36 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
rs505922	7e-27	ABO	C	1.27
rs1219651	1e-25	FGFR2	?	1.09
rs9543325	1e-22	RNY1P8 - MARK2P12	C	1.24
rs2981584	1e-21	FGFR2	?	0.94
rs10908278	3e-21	HNF1B	?	1.06
rs112149573	2e-17	TOX3	?	1.08
rs401681	9e-17	CLPTM1L	T	1.19
rs687289	2e-16	ABO	?	1.27
rs3790844	8e-16	NR5A2	A	1.23
rs78540526	1e-15	LINC01488 - PNCRNA-D	?	1.13
rs35409710	2e-15	HLA-DQB1	?	1.09
rs7463708	2e-15	PCAT1, PRNCR1, CASC19	?	1.08
rs2816938	3e-15	RNU6-609P - NR5A2	A	1.21
rs2736098	7e-15	TERT	C	1.19
rs7214041	9e-15	LINC00511	T	1.25
rs11655237	1e-14	LINC00511	T	1.26
rs11651755	1e-14	HNF1B	?	1.06
rs558740946	2e-14	VAC14	A	3.02
rs9581943	5e-14	PLUT - PDX1	A	1.15
rs6971499	7e-14	LINC-PINT	T	1.23
rs13303010	8e-14	NOC2L	G	1.26
rs1485995	8e-14	LINC01488	?	0.95
rs372883	2e-13	BACH1	T	1.27
rs9273736	2e-13	HLA-DQB1	?	1.12
rs2976384	3e-13	PSCA, JRK	?	1.07
rs1547374	4e-13	TFF2 - TFF1	A	1.27
rs9573163	5e-13	RNY1P8 - MARK2P12	G	1.26
rs72802342	1e-12	ZFP1 - CTRB2	C	0.41
rs182822720	1e-12	GUSBP7 - RNU6-1119P	A	2.76

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90432146	Jiang Y	2023	116,382	213,325	A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.
GCST90651054	Sato G	2023	43,098	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308764	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST005434	Klein AP	2018	9,040	12,496	Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.
GCST007235	Walsh N	2018	9,040	12,496	Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.
GCST90100588	Lu Y	2021	8,769	7,055	Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk.
GCST012178	Mocci E	2021	7,937	11,774	Smoking modifies pancreatic cancer risk loci on 2q21.3.
GCST002991	Childs EJ	2015	7,638	7,364	Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.
GCST003758	Zhang M	2016	5,107	8,845	Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.
GCST90554823	Ni Z	2024	4,805	5,329	Genome-wide analysis to assess if heavy alcohol consumption modifies the association between SNPs and pancreatic cancer risk.

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)	44
low_freq (0.01-0.05)	2
rare (<0.01)	3
unknown	1

Functional consequences

Consequence	Count
intron_variant	30
intergenic_variant	8
regulatory_region_variant	3
non_coding_transcript_exon_variant	3
synonymous_variant	2
3_prime_UTR_variant	1
splice_region_variant	1
unknown	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
rs505922	9	133273813	C>T	0.35	intron_variant	ABO	7e-27	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
rs9543325	13	73342491	C>G,T	0.37	intergenic_variant	RNY1P8 - MARK2P12	1e-22	Tier 4: intronic/intergenic
rs2981584	10	121590702	A>C,G,T	0.05	intron_variant	FGFR2	1e-21	Tier 4: intronic/intergenic
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	3e-21	Tier 4: intronic/intergenic
rs112149573	16	52547333	G>C,T	0.05	intron_variant	TOX3	2e-17	Tier 4: intronic/intergenic
rs401681	5	1321972	C>T	0.44	intron_variant	CLPTM1L	9e-17	Tier 4: intronic/intergenic
rs687289	9	133261703	A>C,G,T	0.05	intron_variant	ABO	2e-16	Tier 4: intronic/intergenic
rs3790844	1	200038304	A>C,G,T	0.23	intron_variant	NR5A2	8e-16	Tier 4: intronic/intergenic
rs78540526	11	69516650	C>T	0.05	regulatory_region_variant	LINC01488 - PNCRNA-D	1e-15	Tier 3: regulatory
rs35409710	6	32661126	G>A	0.05	intron_variant	HLA-DQB1	2e-15	Tier 4: intronic/intergenic
rs7463708	8	127091810	G>A,C,T	0.05	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	2e-15	Tier 4: intronic/intergenic
rs2816938	1	200016240	T>A,G	0.23	intergenic_variant	RNU6-609P - NR5A2	3e-15	Tier 4: intronic/intergenic
rs2736098	5	1293971	C>A,G,T	0.27	synonymous_variant	TERT	7e-15	Tier 4: intronic/intergenic
rs7214041	17	72405335	C>G,T	0.11	intron_variant	LINC00511	9e-15	Tier 4: intronic/intergenic
rs11655237	17	72404025	C>G,T	0.11	intron_variant	LINC00511	1e-14	Tier 4: intronic/intergenic
rs11651755	17	37739849	T>C	0.05	intron_variant	HNF1B	1e-14	Tier 4: intronic/intergenic
rs558740946	16	70752182	A>G	0	intron_variant	VAC14	2e-14	Tier 4: intronic/intergenic
rs9581943	13	27919860	G>A	0.39	regulatory_region_variant	PLUT - PDX1	5e-14	Tier 3: regulatory
rs6971499	7	130995762	T>C	0.16	intron_variant	LINC-PINT	7e-14	Tier 4: intronic/intergenic
rs13303010	1	959193	G>A	0.11	intron_variant	NOC2L	8e-14	Tier 4: intronic/intergenic
rs1485995	11	69492939	G>A,C	0.05	non_coding_transcript_exon_variant	LINC01488	8e-14	Tier 4: intronic/intergenic
rs372883	21	29345416	T>A,C,G	0.05	3_prime_UTR_variant	BACH1	2e-13	Tier 2: splice/UTR
rs9273736	6	32661595	G>A,C	0.05	intron_variant	HLA-DQB1	2e-13	Tier 4: intronic/intergenic
rs2976384	8	142671576	T>A,C	0.05	intergenic_variant	PSCA, JRK	3e-13	Tier 4: intronic/intergenic
rs1547374	21	42358786	A>G,T	0.05	intergenic_variant	TFF2 - TFF1	4e-13	Tier 4: intronic/intergenic
rs9573163	13	73334709	C>G,T	0.43	regulatory_region_variant	RNY1P8 - MARK2P12	5e-13	Tier 3: regulatory
rs72802342	16	75200974	C>A,G,T	0.081	intergenic_variant	ZFP1 - CTRB2	1e-12	Tier 4: intronic/intergenic
rs182822720	5	100109756	A>C	0	intron_variant	GUSBP7 - RNU6-1119P	1e-12	Tier 4: intronic/intergenic

ClinVar germline variants

132 retrieved; paginated sample, class counts are floors:

39 pathogenic, 31 conflicting classifications of pathogenicity, 21 uncertain significance, 14 pathogenic/likely pathogenic, 12 benign/likely benign, 6 likely benign, 3 likely pathogenic, 3 benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 pathogenic/likely pathogenic; association, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
8227	NM_004302.5(ACVR1B):c.1159_1163del (p.Asp387fs)	ACVR1B	Pathogenic	no assertion criteria provided
8228	NM_004302.5(ACVR1B):c.1262-502_1392+24del	ACVR1B	Pathogenic	no assertion criteria provided
181974	NM_000051.4(ATM):c.6095G>A (p.Arg2032Lys)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
246092	NM_000051.4(ATM):c.6096-9_6096-5del	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3036	NM_000051.4(ATM):c.7327C>T (p.Arg2443Ter)	ATM	Pathogenic	criteria provided, multiple submitters, no conflicts
37466	NM_007294.4(BRCA1):c.2411_2412del (p.Gln804fs)	BRCA1	Pathogenic	reviewed by expert panel
37546	NM_007294.4(BRCA1):c.3770_3771del (p.Glu1257fs)	BRCA1	Pathogenic	reviewed by expert panel
54516	NM_007294.4(BRCA1):c.2263G>T (p.Glu755Ter)	BRCA1	Pathogenic	reviewed by expert panel
1077094	NM_000059.4(BRCA2):c.7415dup (p.Cys2473fs)	BRCA2	Pathogenic	no assertion criteria provided
254495	NM_000059.4(BRCA2):c.1989del (p.Phe663fs)	BRCA2	Pathogenic	reviewed by expert panel
37762	NM_000059.4(BRCA2):c.1813dup (p.Ile605fs)	BRCA2	Pathogenic	reviewed by expert panel
37846	NM_000059.4(BRCA2):c.3545_3546del (p.Gln1181_Phe1182insTer)	BRCA2	Pathogenic	reviewed by expert panel
37943	NM_000059.4(BRCA2):c.5073dup (p.Trp1692fs)	BRCA2	Pathogenic	reviewed by expert panel
38099	NM_000059.4(BRCA2):c.7480C>T (p.Arg2494Ter)	BRCA2	Pathogenic	reviewed by expert panel
38183	NM_000059.4(BRCA2):c.8755-1G>A	BRCA2	Pathogenic	reviewed by expert panel
51711	NM_000059.4(BRCA2):c.475G>A (p.Val159Met)	BRCA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
52515	NM_000059.4(BRCA2):c.8167G>C (p.Asp2723His)	BRCA2	Pathogenic	reviewed by expert panel
1077092	NM_032043.3(BRIP1):c.1328_1334del (p.Cys443fs)	BRIP1	Pathogenic	no assertion criteria provided
241642	NM_032043.3(BRIP1):c.2684_2687del (p.Val894_Ser895insTer)	BRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1077093	NM_007194.4(CHEK2):c.908+1540_1095+330del	CHEK2	Pathogenic	criteria provided, single submitter
128042	NM_007194.4(CHEK2):c.1100del (p.Thr367fs)	CHEK2	Pathogenic	criteria provided, multiple submitters, no conflicts
216652	NM_007194.4(CHEK2):c.846+4_846+7del	CHEK2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128031	NM_006361.6(HOXB13):c.251G>A (p.Gly84Glu)	HOXB13	Pathogenic/Likely pathogenic; association	criteria provided, multiple submitters, no conflicts
12582	NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12583	NM_004985.5(KRAS):c.35G>T (p.Gly12Val)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12587	NM_004985.5(KRAS):c.458A>T (p.Asp153Val)	KRAS	Pathogenic	reviewed by expert panel
6940	NM_002485.5(NBN):c.657_661del (p.Lys219fs)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
126757	NM_024675.4(PALB2):c.509_510del (p.Arg170fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1077091	NM_002691.4(POLD1):c.3148del (p.Arg1050fs)	POLD1	Pathogenic	no assertion criteria provided
142253	NM_005359.6(SMAD4):c.1245_1248del (p.Asp415Glufs)	SMAD4	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 158 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
CHEK2	CHEK2	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
CHEK2	Act	BRCA	CIViC #8950
PALB2	LoF	OVT	CIViC #15013
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
SMAD4	LoF	BRCA,CESC,CHOL,COAD,COADREAD,ESCA,ESCC,GBC,HNSC,LUAD,NSCLC,PAAD,PANCREAS,PRAD,PROSTATE,READ,STAD,STOMACH	CIViC #77
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
RRM1			CIViC #5051
RRM2			CIViC #5052
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
SIRT1			CIViC #9538
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
MIR218-1			CIViC #24938
ETV4	Act	NBL	CIViC #1767
FANCC			CIViC #1811
HNF1A	LoF	HCC,PRCC
TERT	Act	PRCC	CIViC #79
TFRC	Act	NSCLC,PRAD
TP63	LoF	BLCA,CESC,HNSC,MEL,NBL
ACVR1B	LoF	BRCA,COAD,COADREAD,LUAD,PAAD
ARID1B	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,COADREAD,DLBCLNOS,HCC,LGGNOS,LUSC,MBL,MLYM,PAAD,PAST,PRAD,PRCC,SACA,STAD,UCEC,WDTC	CIViC #13820
CDX2	LoF	ESCA	CIViC #927
ZNRF3	LoF	ACC
RNF43	LoF	CHOL,COAD,COADREAD,ESCA,LUSC,OVT,PAAD,PANCREAS,PRAD,PROSTATE,STAD,UCEC

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
STK11	Orphanet:2869	Peutz-Jeghers syndrome
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
CHEK2	Orphanet:1331	Familial prostate cancer
CHEK2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
CHEK2	Orphanet:440437	Familial colorectal cancer Type X
CHEK2	Orphanet:524	Li-Fraumeni syndrome
CHEK2	Orphanet:668	Osteosarcoma
PALB2	Orphanet:1333	Familial pancreatic carcinoma
PALB2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PALB2	Orphanet:178	Chordoma

Cohort genes → proteins

75 cohort genes, 73 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	56
gwas_and_clinvar	1
civic_only	8
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	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
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar,civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar,civic_evidence
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	gwas,clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar,civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	gwas,civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar,civic_evidence
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	clinvar,civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar,civic_evidence
RRM1	HGNC:10451	ENSG00000167325	P23921	Ribonucleoside-diphosphate reductase large subunit	civic_evidence
RRM2	HGNC:10452	ENSG00000171848	P31350	Ribonucleoside-diphosphate reductase subunit M2	civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
SIRT1	HGNC:14929	ENSG00000096717	Q96EB6	NAD-dependent protein deacetylase sirtuin-1	civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
MIR218-1	HGNC:31595	ENSG00000207732		microRNA 218-1	civic_evidence
ETV4	HGNC:3493	ENSG00000175832	P43268	ETS translocation variant 4	civic_evidence
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	civic_evidence
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	gwas
RUNX2	HGNC:10472	ENSG00000124813	Q13950	Runt-related transcription factor 2	gwas
BICD1	HGNC:1049	ENSG00000151746	Q96G01	Protein bicaudal D homolog 1	gwas
SLC12A7	HGNC:10915	ENSG00000113504	Q9Y666	Solute carrier family 12 member 7	gwas
SLC1A1	HGNC:10939	ENSG00000106688	P43005	Excitatory amino acid transporter 3	gwas
SLC6A3	HGNC:11049	ENSG00000142319	Q01959	Sodium-dependent dopamine transporter	gwas
MED22	HGNC:11477	ENSG00000148297	Q15528	Mediator of RNA polymerase II transcription subunit 22	gwas
TCAP	HGNC:11610	ENSG00000173991	O15273	Telethonin	gwas
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	gwas
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TFF1	HGNC:11755	ENSG00000160182	P04155	Trefoil factor 1	gwas
TFRC	HGNC:11763	ENSG00000072274	P02786	Transferrin receptor protein 1	gwas
THRA	HGNC:11796	ENSG00000126351	P10827	Thyroid hormone receptor alpha	gwas
LDLRAD4	HGNC:1224	ENSG00000168675	O15165	Low-density lipoprotein receptor class A domain-containing protein 4	gwas
TRIP13	HGNC:12307	ENSG00000071539	Q15645	Pachytene checkpoint protein 2 homolog	gwas
TSGA13	HGNC:12369	ENSG00000213265	Q96PP4	Testis-specific gene 13 protein	gwas
WNT2B	HGNC:12781	ENSG00000134245	Q93097	Protein Wnt-2b	gwas
XBP1	HGNC:12801	ENSG00000100219	P17861	X-box-binding protein 1	gwas
ZNF100	HGNC:12880	ENSG00000197020	Q8IYN0	Zinc finger protein 100	gwas
ZNF207	HGNC:12998	ENSG00000010244	O43670	BUB3-interacting and GLEBS motif-containing protein ZNF207	gwas
RHBDD3	HGNC:1308	ENSG00000100263	Q9Y3P4	Rhomboid domain-containing protein 3	gwas
GABARAPL2	HGNC:13291	ENSG00000034713	P60520	Gamma-aminobutyric acid receptor-associated protein-like 2	gwas
LGR4	HGNC:13299	ENSG00000205213	Q9BXB1	Leucine-rich repeat-containing G-protein coupled receptor 4	gwas
ADAMTS13	HGNC:1366	ENSG00000160323	Q76LX8	A disintegrin and metalloproteinase with thrombospondin motifs 13	gwas
OPN3	HGNC:14007	ENSG00000054277	Q9H1Y3	Opsin-3	gwas
SMC2	HGNC:14011	ENSG00000136824	O95347	Structural maintenance of chromosomes protein 2	gwas
ERO1B	HGNC:14355	ENSG00000086619	Q86YB8	ERO1-like protein beta	gwas
SP6	HGNC:14530	ENSG00000189120	Q3SY56	Transcription factor Sp6	gwas
CAV2	HGNC:1528	ENSG00000105971	P51636	Caveolin-2	gwas
TP63	HGNC:15979	ENSG00000073282	Q9H3D4	Tumor protein 63	gwas
SUGCT	HGNC:16001	ENSG00000175600	Q9HAC7	Succinyl-CoA:glutarate CoA-transferase	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
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…
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CHEK2	Serine/threonine-protein kinase Chk2	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
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.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
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.
RRM1	Ribonucleoside-diphosphate reductase large subunit	Provides the precursors necessary for DNA synthesis.
RRM2	Ribonucleoside-diphosphate reductase subunit M2	Provides the precursors necessary for DNA synthesis.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
SIRT1	NAD-dependent protein deacetylase sirtuin-1	NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolis…
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
ETV4	ETS translocation variant 4	Transcriptional activator.
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
RORA	Nuclear receptor ROR-alpha	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
RUNX2	Runt-related transcription factor 2	Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis.
BICD1	Protein bicaudal D homolog 1	Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport by recruiting the dynein-dynactin motor complex.
SLC12A7	Solute carrier family 12 member 7	Mediates electroneutral potassium-chloride cotransport when activated by cell swelling.
SLC1A1	Excitatory amino acid transporter 3	Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.
SLC6A3	Sodium-dependent dopamine transporter	Mediates sodium- and chloride-dependent transport of dopamine.
MED22	Mediator of RNA polymerase II transcription subunit 22	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
TCAP	Telethonin	Muscle assembly regulating factor.
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3’.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TFF1	Trefoil factor 1	Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents.
TFRC	Transferrin receptor protein 1	Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes.
THRA	Thyroid hormone receptor alpha	Nuclear hormone receptor that can act as a repressor or activator of transcription.
LDLRAD4	Low-density lipoprotein receptor class A domain-containing protein 4	Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression.
TRIP13	Pachytene checkpoint protein 2 homolog	Plays a key role in chromosome recombination and chromosome structure development during meiosis.
WNT2B	Protein Wnt-2b	Ligand for members of the frizzled family of seven transmembrane receptors.
XBP1	X-box-binding protein 1	Functions as a transcription factor during endoplasmic reticulum (ER) stress by regulating the unfolded protein response (UPR).
ZNF100	Zinc finger protein 100	May be involved in transcriptional regulation.
ZNF207	BUB3-interacting and GLEBS motif-containing protein ZNF207	Kinetochore- and microtubule-binding protein that plays a key role in spindle assembly.
GABARAPL2	Gamma-aminobutyric acid receptor-associated protein-like 2	Ubiquitin-like modifier involved in intra-Golgi traffic.
LGR4	Leucine-rich repeat-containing G-protein coupled receptor 4	Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs.
ADAMTS13	A disintegrin and metalloproteinase with thrombospondin motifs 13	Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.
OPN3	Opsin-3	G protein-coupled receptor which selectively activates G(i/o) proteins via ultraviolet A (UVA) light-mediated activation in the skin, thereby decreasing cellular cAMP.
SMC2	Structural maintenance of chromosomes protein 2	Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes.
ERO1B	ERO1-like protein beta	Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum.
SP6	Transcription factor Sp6	Promotes cell proliferation.
CAV2	Caveolin-2	May act as a scaffolding protein within caveolar membranes.
TP63	Tumor protein 63	Acts as a sequence specific DNA binding transcriptional activator or repressor.
SUGCT	Succinyl-CoA:glutarate CoA-transferase	Coenzyme A (CoA) transferase that reversibly catalyzes the transfer of a CoA moiety from a dicarboxyl-CoA to a dicarboxylate in a metabolite recycling process.
WHRN	Whirlin	Involved in hearing and vision as member of the USH2 complex.
IL17F	Interleukin-17F	Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.
RASL10A	Ras-like protein family member 10A	Potent inhibitor of cellular proliferation.

Protein-family classification

Druggable: 21 · Difficult: 18 · Unknown: 36 · Druggable fraction: 0.28

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
Nuclear receptor	2	10.3×	0.083
Kinase	7	2.6×	0.083
Transcription factor	13	1.4×	0.347
Complement	1	3.6×	0.551
Protease	3	1.5×	0.606
Scaffold/PPI	5	1.1×	0.658
Enzyme (other)	6	1.0×	0.775
GPCR	2	0.6×	0.930
Other/Unknown	36	0.9×	0.930

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
RRM1	Enzyme (other)	yes	1.17.4.1	RNR_lg_C, ATP-cone_dom, RNR_R1-su_N
RRM2	Enzyme (other)	yes	1.17.4.1	RNR_small_fam, Ferritin-like_SF, RNR-like
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
SIRT1	Enzyme (other)	yes	2.3.1.286	Sirtuin, Ssirtuin_cat_dom, Sirtuin_cat_small_dom_sf
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
MIR218-1	Other/Unknown	no
ETV4	Other/Unknown	no		Ets_dom, ETS_PEA3_N, WH-like_DNA-bd_sf
FANCC	Other/Unknown	no		FANCC
RORA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RUNX2	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
BICD1	Other/Unknown	no		BICD
SLC12A7	Other/Unknown	no		KCL_cotranspt, AA-permease/SLC12A_dom, SLC12A_fam
SLC1A1	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf
SLC6A3	Other/Unknown	no		Na/ntran_symport, Na/ntran_symport_dopamine, SNS_sf
MED22	Other/Unknown	no		Med22
TCAP	Other/Unknown	no		Telethonin, Titin-like_dom_sf
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TFF1	Other/Unknown	no		P_trefoil_dom, P_trefoil_CS, P_trefoil_chordata
TFRC	Protease	yes		PA_domain, TFR-like_dimer_dom, Peptidase_M28
THRA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
LDLRAD4	Other/Unknown	no		LDrepeatLR_classA_rpt, LDLR_class-A_CS, LDL_receptor-like_sf
TRIP13	Other/Unknown	no		ClpA/B, AAA+_ATPase, ATPase_AAA_core
TSGA13	Other/Unknown	no		TSGA13
WNT2B	Other/Unknown	no		Wnt, Wnt2, Wnt_CS
XBP1	Transcription factor	no		bZIP, bZIP_sf, ER_Stress-Reg_TF
ZNF100	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZNF207	Transcription factor	no		Znf_C2H2_type
RHBDD3	Protease	yes		UBA-like_sf, UBA, Peptidase_S54_rhomboid_dom
GABARAPL2	Other/Unknown	no		Atg8-like, Ubiquitin-like_domsf
LGR4	GPCR	yes		GPCR_Rhodpsn, LRRNT, Leu-rich_rpt
ADAMTS13	Protease	yes	3.4.24.87	TSP1_rpt, Peptidase_M12B, ADAM_Cys-rich
OPN3	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Retinal_BS
SMC2	Other/Unknown	no		RecF/RecN/SMC_N, SMC_hinge, SMC
ERO1B	Other/Unknown	no		Ero1, ERO1-like_sf
SP6	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
CAV2	Other/Unknown	no		Caveolin, Caveolin_CS
TP63	Transcription factor	no		SAM, p53_tumour_suppressor, p53-like_TF_DNA-bd_sf
SUGCT	Enzyme (other)	yes	2.8.3.13	CoA-Trfase_fam_III, CoA-Trfase_III_dom_1_sf, CoA-Trfase_III_dom3_sf

Expression context

Cohort genes with no expression data: 0.

65 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)	1
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	11
male germ line stem cell (sensu Vertebrata) in testis	10
calcaneal tendon	8
ganglionic eminence	7
primordial germ cell in gonad	6
mucosa of transverse colon	6
secondary oocyte	5
buccal mucosa cell	5
right lobe of liver	5
apex of heart	5
oocyte	4
sural nerve	4
cervix squamous epithelium	4
liver	4
upper arm skin	4
right testis	3
lower esophagus mucosa	3
colonic epithelium	3
adrenal tissue	3
pancreatic ductal cell	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
SMAD4	288	ubiquitous	marker	ventricular zone, ganglionic eminence, calcaneal tendon
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
RRM1	296	ubiquitous	marker	ventricular zone, ganglionic eminence, cervix squamous epithelium
RRM2	233	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
SIRT1	280	ubiquitous	marker	calcaneal tendon, ganglionic eminence, ventricular zone
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
MIR218-1	66		yes	kidney, calcaneal tendon, adrenal tissue
ETV4	171	ubiquitous	marker	primordial germ cell in gonad, type B pancreatic cell, olfactory bulb
FANCC	195	ubiquitous	marker	pancreatic ductal cell, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
RORA	284	ubiquitous	marker	upper leg skin, lateral nuclear group of thalamus, skin of hip
RUNX2	241	ubiquitous	marker	tibia, mucosa of paranasal sinus, trabecular bone tissue
BICD1	259	ubiquitous	marker	ventricular zone, sural nerve, ganglionic eminence
SLC12A7	140	ubiquitous	marker	apex of heart, heart left ventricle, metanephros cortex
SLC1A1	248	ubiquitous	marker	corpus epididymis, jejunal mucosa, ileal mucosa
SLC6A3	84	tissue_specific	marker	substantia nigra, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
MED22	134	ubiquitous	yes	cortical plate, granulocyte, lower esophagus muscularis layer
TCAP	213	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis
HNF1A	81	tissue_specific	yes	right lobe of liver, mucosa of transverse colon, liver
HNF1B	74	broad	marker	metanephros cortex, adult mammalian kidney, kidney
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TFF1	172	broad	marker	pancreatic ductal cell, endometrium epithelium, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 61.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
ERBB2	9,659
CDKN2A	9,311
BRCA1	9,064
SIRT1	8,285
BRAF	7,394
ATM	7,383
SMAD4	7,320
TFRC	6,725

Intra-cohort edges

A	B	Sources
ACVR1B	SMAD4	intact, string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	STK11	string_interaction
ATM	TFF1	biogrid_interaction, intact
ATM	TP53	biogrid_interaction, string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CDKN2A	string_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	RNF43	intact
BRAF	TP53	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	TP53	string_interaction
BRCA1	TP63	biogrid_interaction
BRCA2	CHEK2	string_interaction
BRCA2	FANCC	string_interaction
BRCA2	PALB2	biogrid_interaction, intact, string_interaction
BRCA2	STK11	string_interaction
BRCA2	TP53	string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	RNF43	string_interaction
CDKN2A	TP53	string_interaction
CDKN2A	TP63	string_interaction
CDX2	HNF1A	biogrid_interaction, string_interaction
CHEK2	PALB2	string_interaction
CHEK2	SIRT1	biogrid_interaction
CHEK2	SMC2	intact
CHEK2	TP53	intact, string_interaction
CHEK2	TP63	biogrid_interaction, intact
ERBB2	KRAS	string_interaction
ERO1B	XBP1	string_interaction
ETV4	STK11	biogrid_interaction
FANCC	PALB2	string_interaction
FANCC	SMAD4	intact
GABARAPL2	SIRT1	string_interaction
GAS2L1	RASL10A	string_interaction
HNF1A	HNF1B	biogrid_interaction, intact, string_interaction
HNF1A	SMAD4	intact
IL17F	RORA	intact
KRAS	RNF43	string_interaction
KRAS	STK11	string_interaction
KRAS	TP53	string_interaction
KREMEN1	ZNRF3	string_interaction
LGR4	LIN7C	string_interaction
LGR4	RNF43	string_interaction
LGR4	ZNRF3	biogrid_interaction, intact, string_interaction
LIN7C	SLC6A3	intact

Structural data

PDB: 51 · AlphaFold-only: 22 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
BRAF	P15056	131
ERBB2	P04626	63
CHEK2	O96017	38
BRCA1	P38398	33
TP63	Q9H3D4	26
TFRC	P02786	24
TERT	O14746	23
LGR4	Q9BXB1	23
SLC1A1	P43005	22
SLC6A3	Q01959	17
BRCA2	P51587	14
ATM	Q13315	14
SMAD4	Q13485	12
RRM1	P23921	12
MED22	Q15528	11
THRA	P10827	10
SIRT1	Q96EB6	9
IL17F	Q96PD4	9
KREMEN1	Q96MU8	9
ZNRF3	Q9ULT6	8
FANCC	Q00597	6
HNF1A	P20823	6
TRIP13	Q15645	6
RRM2	P31350	5
CDKN2A	P42771	5
XBP1	P17861	5
GABARAPL2	P60520	5
ADAMTS13	Q76LX8	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
URAD	A6NGE7	95.44
LDHD	Q86WU2	89.11
CHST5	Q9GZS9	88.60
WNT2B	Q93097	86.85
RASL10A	Q92737	81.77
OPN3	Q9H1Y3	80.71
CAV2	P51636	78.26
ERO1B	Q86YB8	76.40
ZDHHC11	Q9H8X9	74.62
HPS5	Q9UPZ3	73.21
BICD1	Q96G01	72.36
RHBDD3	Q9Y3P4	69.46
ZNF100	Q8IYN0	67.97
CFDP1	Q9UEE9	64.86
ZNF207	O43670	61.30
GAS2L1	Q99501	60.82
TSGA13	Q96PP4	60.38
LDLRAD4	O15165	58.44
NDFIP2	Q9NV92	57.15
NKD2	Q969F2	56.15
SP6	Q3SY56	52.79
EMID1	Q96A84	51.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 708. Enrichment computed across 183 evidence-associated genes (115 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 115 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 binding to PALB2	7	27.8×	1e-06	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, RBBP8
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	7	25.8×	1e-06	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, RBBP8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	7	25.8×	1e-06	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, RBBP8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	7	25.8×	1e-06	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, RBBP8
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	7	24.0×	2e-06	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, RBBP8
Homologous DNA Pairing and Strand Exchange	7	23.2×	2e-06	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, RBBP8
Resolution of D-loop Structures through Holliday Junction Intermediates	7	18.3×	9e-06	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, RBBP8
HDR through Homologous Recombination (HRR)	8	13.2×	1e-05	BRCA1, BRCA2, PALB2, ATM, BRIP1, NBN, POLD1, RBBP8
Regulation of TP53 Activity through Phosphorylation	9	9.2×	4e-05	BRCA1, STK11, TP53, CHEK2, ATM, BRIP1, NOC2L, NBN (+1 more)
Impaired BRCA2 binding to RAD51	6	16.1×	1e-04	BRCA1, BRCA2, ATM, BRIP1, NBN, RBBP8
HDR through Single Strand Annealing (SSA)	6	15.3×	1e-04	BRCA1, ATM, BRIP1, ERCC4, NBN, RBBP8
Presynaptic phase of homologous DNA pairing and strand exchange	6	14.2×	2e-04	BRCA1, BRCA2, ATM, BRIP1, NBN, RBBP8
Defective homologous recombination repair (HRR) due to PALB2 loss of function	4	33.1×	2e-04	BRCA1, BRCA2, ATM, NBN
Diseases of DNA Double-Strand Break Repair	4	28.4×	4e-04	BRCA1, BRCA2, ATM, NBN
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	4	28.4×	4e-04	BRCA1, BRCA2, ATM, NBN
Stabilization of p53	4	26.5×	5e-04	TP53, CHEK2, ATM, CDKN2A
Resolution of D-Loop Structures	4	22.1×	0.001	BRCA1, BRCA2, ATM, NBN
Diseases of DNA repair	4	19.9×	0.002	BRCA1, BRCA2, ATM, NBN
G2/M DNA damage checkpoint	7	7.3×	0.002	BRCA1, TP53, CHEK2, ATM, BRIP1, NBN, RBBP8
TP53 Regulates Transcription of Caspase Activators and Caspases	3	24.8×	0.007	TP53, ATM, TP63
HDR through MMEJ (alt-NHEJ)	3	22.9×	0.009	BRCA2, NBN, RBBP8
Nuclear Receptor transcription pathway	5	8.7×	0.009	RORA, THRA, HNF4A, HNF4G, NR5A2
TP53 Regulates Transcription of DNA Repair Genes	5	7.9×	0.012	BRCA1, TP53, ATM, FANCC, GTF2H1
MITF-M-dependent gene expression	5	7.9×	0.012	BRCA1, TERT, SIRT1, CDKN2A, ARID1B
Homology Directed Repair	4	10.7×	0.013	BRCA1, BRCA2, ATM, NBN
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	4	10.7×	0.013	BRCA1, BRCA2, ATM, NBN
MITF-M-regulated melanocyte development	6	6.0×	0.013	BRCA1, TERT, SIRT1, CDKN2A, ARID1B, KARS1
Regulation of TP53 Degradation	4	10.2×	0.015	TP53, CHEK2, ATM, CDKN2A
Meiosis	4	9.9×	0.016	BRCA1, BRCA2, ATM, NBN
Fanconi Anemia Pathway	4	9.7×	0.017	ERCC4, FANCC, FANCE, FANCG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 156 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
replicative senescence	5	31.8×	5e-04	TP53, CHEK2, ATM, TERT, CDKN2A
double-strand break repair	8	10.4×	7e-04	BRCA1, BRCA2, TP53, CHEK2, ATM, TRIP13, BRIP1, NBN
homologous recombination	4	36.0×	0.001	BRCA1, BRIP1, NBN, RBBP8
nucleotide-excision repair	6	14.7×	0.001	BRCA2, TP53, BRIP1, ERCC4, FANCC, GTF2H1
double-strand break repair via homologous recombination	8	8.0×	0.002	BRCA1, BRCA2, PALB2, ATM, BRD9, ERCC4, NBN, RBBP8
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	5	15.9×	0.003	BRCA2, TP53, CHEK2, SIRT1, TP63
negative regulation of cell growth	8	7.4×	0.003	BRCA1, STK11, TP53, SMAD4, ACVR1B, CDKN2A, DAB2, HNF4A
DNA strand resection involved in replication fork processing	3	40.5×	0.006	BRCA1, NBN, RBBP8
mitotic G2/M transition checkpoint	4	20.6×	0.006	BRCA1, ETAA1, NBN, RBBP8
cellular response to xenobiotic stimulus	6	9.3×	0.006	TP53, CHEK2, BRAF, TFRC, RNF149, MYC
DNA repair	11	4.5×	0.006	BRCA1, RRM1, RRM2, BRIP1, ETAA1, ERCC4, FANCC, FANCG (+3 more)
positive regulation of DNA-templated transcription	17	3.0×	0.006	BRCA1, BRCA2, TP53, CHEK2, SMAD4, RORA, RUNX2, HNF1A (+9 more)
negative regulation of canonical Wnt signaling pathway	8	6.0×	0.006	STK11, SMAD4, NKD2, KREMEN1, ZNRF3, DAB2, IGFBP4, PRKN
positive regulation of gene expression	14	3.5×	0.006	BRCA1, TP53, KRAS, SMAD4, ATM, RUNX2, BRAF, HNF1B (+6 more)
DNA damage response, signal transduction by p53 class mediator	5	11.5×	0.007	BRCA2, TP53, CHEK2, ATM, NBN
Wnt receptor catabolic process	2	108.0×	0.008	ZNRF3, RNF43
positive regulation of transcription by RNA polymerase II	24	2.3×	0.010	BRCA1, TP53, SMAD4, ATM, RORA, RUNX2, HNF1A, THRA (+16 more)
stem cell proliferation	5	10.0×	0.012	TP53, RUNX2, TP63, ZNRF3, RNF43
regulation of glucose metabolic process	4	14.4×	0.013	RORA, SIRT1, IGFBP4, PRKN
cellular response to UV	5	9.5×	0.013	TP53, NOC2L, ERCC4, MYC, POLD1
cellular senescence	5	9.5×	0.013	BRCA2, TP53, ATM, TP63, CDKN2A
positive regulation of cellular senescence	3	24.9×	0.014	TP53, KRAS, SIRT1
ribonucleoside diphosphate metabolic process	2	72.0×	0.015	RRM1, RRM2
deoxyribonucleotide biosynthetic process	2	72.0×	0.015	RRM1, RRM2
2’-deoxyribonucleotide biosynthetic process	2	72.0×	0.015	RRM1, RRM2
positive regulation of macrophage apoptotic process	2	72.0×	0.015	SIRT1, CDKN2A
regulation of DNA damage checkpoint	3	21.6×	0.018	BRCA1, BRCA2, ETAA1
regulation of transcription by RNA polymerase II	27	2.0×	0.018	BRCA1, TP53, SMAD4, RORA, RUNX2, HNF1A, HNF1B, THRA (+19 more)
transcription by RNA polymerase II	9	4.1×	0.020	SMAD4, THRA, TRIP13, XBP1, TP63, GSX1, GTF2H1, HNF4A (+1 more)
left ventricular cardiac muscle tissue morphogenesis	2	54.0×	0.020	SMAD4, EDNRA

Therapeutics

Drugs indicated for this disease

3 approved, 46 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Everolimus	Approved (phase 4)
Olaparib	Approved (phase 4)
Paclitaxel	Approved (phase 4)
Albumin Human	Phase 3 (in late-stage trials)
Algenpantucel-L	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Bupivacaine	Phase 3 (in late-stage trials)
CPI 613	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Canakinumab	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Cetuximab	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Curcumin	Phase 3 (in late-stage trials)
Dalteparin Sodium	Phase 3 (in late-stage trials)
Erlotinib	Phase 3 (in late-stage trials)
Fentanyl	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Fluzoparib	Phase 3 (in late-stage trials)
G17DT IMMUNOGEN	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Gimeracil	Phase 3 (in late-stage trials)
Glufosfamide	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Irinotecan Sucrosofate	Phase 3 (in late-stage trials)
Irofulven	Phase 3 (in late-stage trials)
Levocarnitine	Phase 3 (in late-stage trials)
Masitinib	Phase 3 (in late-stage trials)
Mitomycin	Phase 3 (in late-stage trials)
Nimotuzumab	Phase 3 (in late-stage trials)
Octreotide	Phase 3 (in late-stage trials)
Oteracil	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Pamrevlumab	Phase 3 (in late-stage trials)
Pasireotide	Phase 3 (in late-stage trials)
Pegilodecakin	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Racemetyrosine	Phase 3 (in late-stage trials)
Rocuronium	Phase 3 (in late-stage trials)
Rubitecan	Phase 3 (in late-stage trials)
Ruxolitinib	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)
Spartalizumab	Phase 3 (in late-stage trials)
Tegafur	Phase 3 (in late-stage trials)
Tertomotide	Phase 3 (in late-stage trials)
Uridine Triacetate	Phase 3 (in late-stage trials)
YTTRIUM Y 90 CLIVATUZUMAB TETRAXETAN	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Acalabrutinib, Adebrelimab, Alvocidib, Arsenic Trioxide, Ascorbic Acid, Aspirin, Atezolizumab, Avelumab, Azacitidine, Balstilimab, Bavituximab, Bethanechol, Binimetinib, Bortezomib, Cabozantinib, Cadonilimab, Calcitriol, Calcium, Carboplatin, Catequentinib, Cemiplimab, Ciprofloxacin, Cirmtuzumab, Dalpiciclib, Dasatinib Anhydrous, Defactinib, Denileukin Diftitox, Dexamethasone, Digoxin, Dipyridamole, Disitamab Vedotin, Disulfiram, Dociparstat Sodium, Dostarlimab, Doxorubicin, Durvalumab, Efavirenz, Encorafenib, Enfortumab Vedotin, Enoxaparin Sodium, Epirubicin, Epoetin Alfa, Etoposide, Famitinib, Filgrastim, Fosgemcitabine Palabenamide, Fruquintinib, Ganetespib, Glipizide, Glutathione, Hydroxychloroquine, INTERFERON ALFA-2B, Ifosfamide, Incomplete Freund’S Adjuvant, Influenza Virus Vaccine, Interferon Alfa, Ipilimumab, Ixabepilone, Lapatinib, Lenalidomide, Losartan, Metenkefalin, Metformin, Methoxsalen, Metronidazole, Milademetan, Minocycline, Niraparib, Nirogacestat, Nivolumab, Nogapendekin Alfa, Oleclumab, Onabotulinumtoxina, Ondansetron, Pancrelipase, Panitumumab, Panobinostat, Paricalcitol, Pazopanib, Pegfilgrastim, Pembrolizumab, Pemetrexed, Pemigatinib, Perifosine, Pertuzumab, Phenytoin, Pioglitazone, Plerixafor, Propranolol, QS-21, Raltitrexed, Ramucirumab, Regorafenib, Retifanlimab, Rintatolimod, Rivoceranib, Rucaparib, Selumetinib, Serine, Simvastatin, Sintilimab, Sirolimus, Sorafenib, Streptozocin, Sunitinib, Surufatinib, Tacedinaline, Tadalafil, Telotristat Ethyl, Temozolomide, Temsirolimus, Tigatuzumab, Tipifarnib, Tislelizumab, Tocilizumab, Toripalimab, Trabectedin, Trametinib, Transplatin, Trastuzumab, Tremelimumab, Tretinoin, Triapine, Trilaciclib, Ubidecarenone, Valproic Acid, Vandetanib, Veliparib, Vemurafenib, Verteporfin, Vismodegib, Volociximab, Zimberelimab.

Drug target analysis

Approved (phase 4): 16 · Phase ≥3: 19 · Phased (≥1): 20 · Undrugged: 55

Druggability breadth: 68 of 183 evidence-associated genes (37%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRCA1	RIBOFLAVIN
STK11	FEDRATINIB
TP53	NITROFURANTOIN
CHEK2	NERATINIB
ERBB2	CLOTRIMAZOLE
KRAS	VEMURAFENIB
ATM	AMIODARONE HYDROCHLORIDE
BRAF	VEMURAFENIB
SIRT1	NIACINAMIDE
RORA	TRETINOIN
SLC6A3	CETIRIZINE
TERT	BERBERINE
THRA	LIOTHYRONINE
XBP1	TERFENADINE
SMC2	SELUMETINIB
ACVR1B	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC6A3	466	4
TP53	196	4
ERBB2	83	4
BRAF	48	4
ATM	35	4
CHEK2	30	4
ACVR1B	21	4
STK11	17	4
BRCA1	12	4
THRA	12	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, SLC6A3, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
FEDRATINIB	4	ACVR1B, BRAF, SLC6A3, STK11
PACRITINIB	4	STK11
NINTEDANIB	4	ACVR1B, STK11
SUNITINIB	4	CHEK2, SLC6A3, STK11
MIDOSTAURIN	4	STK11
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	SLC6A3, TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ERBB2, SLC6A3, TP53
COLCHICINE	4	TP53
NABUMETONE	4	SLC6A3, TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	SLC6A3, TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 16.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
SLC6A3	1,043	Binding:993, Functional:24, ADMET:24, Toxicity:2
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
CHEK2	690	Binding:687, Functional:2, ADMET:1
SIRT1	645	Binding:642, ADMET:3
TERT	391	Binding:389, Functional:2
ACVR1B	286	Binding:282, ADMET:3, Functional:1
STK11	244	Binding:244
ATM	240	Binding:233, Functional:5, ADMET:2
THRA	140	Binding:115, Functional:23, ADMET:2
RORA	115	Binding:111, Functional:3, Unclassified:1
RRM1	83	Binding:80, Functional:3
SLC1A1	50	Binding:43, Functional:7
RRM2	37	Binding:34, Functional:3
BRCA1	13	Binding:9, Functional:4
ZNF207	12	Binding:12
TRIP13	9	Binding:9
XBP1	7	Binding:6, Functional:1
SMAD4	6	Binding:6
STARD3	5	Binding:5
ADAMTS13	3	Binding:3
CDKN2A	2	Binding:2
GABARAPL2	2	Binding:2
LGR4	2	Binding:2
OPN3	2	Binding:2
SMC2	2	Binding:2
IL17F	2	Binding:2
HNF1A	1	Binding:1
TFRC	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
RRM1	1.17.4.1	ribonucleoside-diphosphate reductase
RRM2	1.17.4.1	ribonucleoside-diphosphate reductase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
SIRT1	2.3.1.286	protein acetyllysine N-acetyltransferase
ADAMTS13	3.4.24.87	ADAMTS13 endopeptidase
SUGCT	2.8.3.13	succinate-hydroxymethylglutarate CoA-transferase
ACVR1B	2.7.10.2	non-specific protein-tyrosine kinase
CLYBL	4.1.3.6	citrate (pro-3S)-lyase
RNF43	2.3.2.27	RING-type E3 ubiquitin transferase
LDHD	1.1.2.4	D-lactate dehydrogenase (cytochrome)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
STK11	244
TP53	869
CHEK2	690
ERBB2	1,221
KRAS	861
ATM	240
BRAF	1,442
SIRT1	645
RORA	115
SLC6A3	1,043
TERT	391
THRA	140
ACVR1B	286

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; 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)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1, SLC6A3, TP53
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	ATM, BRCA1
FEDRATINIB	4	ACVR1B, BRAF, SLC6A3, STK11
PACRITINIB	4	STK11
NINTEDANIB	4	ACVR1B, STK11
SUNITINIB	4	CHEK2, SLC6A3, STK11
MIDOSTAURIN	4	STK11
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	SLC6A3, TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	ERBB2, SLC6A3, TP53
COLCHICINE	4	TP53
NABUMETONE	4	SLC6A3, TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	SLC6A3, TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	16	BRCA1, STK11, TP53, CHEK2, ERBB2, KRAS, ATM, BRAF, SIRT1, RORA (+6 more)
B	Phased (≥1) drug, not yet approved	4	RRM1, RRM2, SLC1A1, ZNF207
C	Druggable family + PDB, no drug	6	TFRC, LGR4, ADAMTS13, SUGCT, ASTN2, CLYBL
D	Druggable family + AlphaFold only, no drug	3	RHBDD3, OPN3, LDHD
E	Difficult family or no structure, no drug	46	BRCA2, PALB2, SMAD4, CDKN2A, MIR218-1, ETV4, FANCC, RUNX2, BICD1, SLC12A7 (+36 more)

Undrugged target profiles

55 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
SMAD4	6	—
CDKN2A	2	—
MIR218-1	0	—
ETV4	0	—
FANCC	0	—
RUNX2	0	—
BICD1	0	—
SLC12A7	0	—
MED22	0	—
TCAP	0	—
HNF1A	1	—
HNF1B	0	—
TFF1	0	—
TFRC	1	—
LDLRAD4	0	—
TRIP13	9	—
TSGA13	0	—
WNT2B	0	—
ZNF100	0	—
RHBDD3	0	—
GABARAPL2	2	—
LGR4	2	—
ADAMTS13	3	—
OPN3	2	—
ERO1B	0	—
SP6	0	—
CAV2	0	—
TP63	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,737.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	656
PHASE1/PHASE2	250
PHASE3	134
PHASE4	31
PHASE2/PHASE3	29

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04025840	PHASE4	ACTIVE_NOT_RECRUITING	Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery
NCT05035147	PHASE4	RECRUITING	Albumin-bound Paclitaxel Combined With Gemcitabine First-line Inoperable Pancreatic Cancer
NCT05245877	PHASE4	RECRUITING	Pre- Vs. Postoperative Thromboprophylaxis in Pancreatic Surgery
NCT05784311	PHASE4	RECRUITING	Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)
NCT06779318	PHASE4	NOT_YET_RECRUITING	Maintenance Chemotherapy With S-1 vs. Observation After Adjuvant Therapy for Resected Pancreatic Cancer With High Risk of Recurrence/Metastasis
NCT07557394	PHASE4	NOT_YET_RECRUITING	A Prospective Non-randomized Controlled Interventional Study on the Effect of Shouhui Tongbian Capsules Combined With Pancreatin Enteric-coated Capsules on Pancreatic Exocrine Function in Patients After Curative Resection for Pancreatic Cancer
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00578279	PHASE4	COMPLETED	Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN)With Alcohol in Unresectable Pancreatic Cancer: a Pilot Study
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00642733	PHASE4	TERMINATED	A Study of First Line Treatment With Tarceva (Erlotinib) in Combination With Gemcitabine in Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00920023	PHASE4	COMPLETED	Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI)
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT01768988	PHASE4	TERMINATED	Efficacy Of Pregabalin In The Treatment Of Pancreatic Cancer Pain. A Randomized Controlled Double-Blind, Parallel Group Study
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02044224	PHASE4	COMPLETED	Effects of Dexmedetomidine During IRE Procedures for Solid Tumours
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03891979	PHASE4	WITHDRAWN	Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
NCT04058236	PHASE4	UNKNOWN	Glycocalyx Levels in Patients Undergoing Pancreatectomy
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04217096	PHASE4	UNKNOWN	Efficacy and Safety of Paclitaxel Liposome and S-1 as First-line Therapy in \ Advanced Pancreatic Cancer Patients
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04809935	PHASE4	UNKNOWN	EUS-Coeliac Plexus Block Versus Radiofrequency Ablation in Pain Relief of Patients With Malignancy
NCT06316908	PHASE4	COMPLETED	Permanent Celiac Plexus Block: Comparison of Pain Score in Unilateral and Bilateral Posterior Percutaneous Approach
NCT02000089	PHASE3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT02919787	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Nordic Pancreatic Cancer Trial (NorPACT) - 1
NCT03257033	PHASE3	RECRUITING	Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC
NCT03755739	PHASE2/PHASE3	RECRUITING	Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors
NCT03899636	PHASE3	ACTIVE_NOT_RECRUITING	A Pivotal Study of Safety and Effectiveness of NanoKnife IRE for Stage 3 Pancreatic Cancer
NCT04340141	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer
NCT04927780	PHASE3	ACTIVE_NOT_RECRUITING	Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
NCT05254171	PHASE2/PHASE3	RECRUITING	Study of Nab-Paclitaxel and Gemcitabine With or Without SBP-101 in Pancreatic Cancer
NCT05653453	PHASE3	RECRUITING	Clinical Study of Tumor Treating Fields Combined with Gemcitabine and Albumin-bound Paclitaxel in the First-line Treatment of Locally Advanced Pancreatic Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OXALIPLATIN	4	77
GEMCITABINE	4	37
IRINOTECAN	4	19
ERLOTINIB	4	14
LEUCOVORIN	4	10
SARGRAMOSTIM	4	7
SORAFENIB	4	7
FLUOROURACIL	4	6
CAPECITABINE	4	5
DALTEPARIN SODIUM	4	5
PANITUMUMAB	4	5
DASATINIB ANHYDROUS	4	4
MITOMYCIN	4	4
RUXOLITINIB	4	3
SELUMETINIB	4	3
VISMODEGIB	4	3
ALBUMIN HUMAN	4	2
ALCOHOL	4	2
CALCITRIOL	4	2
EPIRUBICIN HYDROCHLORIDE	4	2
IXABEPILONE	4	2
PACLITAXEL	4	2
PAZOPANIB	4	2
STREPTOZOCIN	4	2
SUNITINIB MALATE	4	2
TIPIRACIL HYDROCHLORIDE	4	2
VORINOSTAT	4	2
ALDESLEUKIN	4	1
ARSENIC TRIOXIDE	4	1
BEVACIZUMAB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 55 predictive associations from 61 curated evidence items; also 10 prognostic, 3 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
BRCA2 Mutation	Rucaparib	Sensitivity/Response	CIViC B	EID7436 +3
BRCA1 Mutation	Rucaparib	Sensitivity/Response	CIViC B	EID9291 +1
RRM1 Underexpression	Gemcitabine	Sensitivity/Response	CIViC B	EID5506 +1
BRCA1 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID5914
BRCA1 Mutation	Cisplatin + Oxaliplatin	Sensitivity/Response	CIViC B	EID5915
BRCA1 Mutation	Cisplatin + Gemcitabine + Veliparib	Sensitivity/Response	CIViC B	EID5932
BRCA1 Mutation	Veliparib	Sensitivity/Response	CIViC B	EID5934
BRCA2 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID5913
BRCA2 Mutation	Platinum Compound	Sensitivity/Response	CIViC B	EID5916
BRCA2 Mutation	Cisplatin + Gemcitabine + Veliparib	Sensitivity/Response	CIViC B	EID5933
BRCA2 Mutation	Veliparib	Sensitivity/Response	CIViC B	EID5935
CDKN2A Loss OR CDKN2A Mutation	Palbociclib	Sensitivity/Response	CIViC B	EID11653
CDKN2A Mutation	Palbociclib	Sensitivity/Response	CIViC B	EID7299
ERBB2 Amplification	Trastuzumab + Pertuzumab	Sensitivity/Response	CIViC B	EID5985
ERBB2 Overexpression	Trastuzumab + Capecitabine	Sensitivity/Response	CIViC B	EID5955
ERBB2 Overexpression	Trastuzumab + Gemcitabine	Sensitivity/Response	CIViC B	EID5956
KRAS Activating Mutation	Salirasib	Sensitivity/Response	CIViC B	EID7180
KRAS G12C	Sotorasib	Sensitivity/Response	CIViC B	EID11680
PALB2 Mutation	Rucaparib	Sensitivity/Response	CIViC B	EID9294
TP53 Mutation	Gemcitabine	Sensitivity/Response	CIViC B	EID8282
KRAS Exon 2 Mutation	Erlotinib + Gemcitabine	Resistance	CIViC B	EID1219
NTRK1 Fusion	Larotrectinib	Sensitivity/Response	CIViC C	EID6051 +1
BRAF N486_P490del	Trametinib	Sensitivity/Response	CIViC C	EID7730
BRAF V600E AND ERBB2 Amplification AND SMAD4 LOSS AND TP53 V218E	Trastuzumab + Bevacizumab + Lapatinib + Trametinib	Sensitivity/Response	CIViC C	EID11712
BRCA2 Mutation	Iniparib	Sensitivity/Response	CIViC C	EID5936
CUX1::BRAF Fusion	Vemurafenib	Sensitivity/Response	CIViC C	EID5977
KRAS G12D AND CDKN2A p16 R80*	Trametinib + Afatinib + Palbociclib	Sensitivity/Response	CIViC C	EID11713
KRAS G12D AND GNAS R201C AND NF1 D1976fs	Trametinib	Sensitivity/Response	CIViC C	EID11714
KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND SMAD4 Deletion AND TP53 R267W	Trametinib + Palbociclib + Bevacizumab	Sensitivity/Response	CIViC C	EID11711
KRAS G12D AND KRAS G12R AND CDKN2A Loss AND CDKN2B Loss AND TP53 R267W	Palbociclib + Trametinib + Bevacizumab	Sensitivity/Response	CIViC C	EID11710

+25 more predictive associations (showing top 30 by evidence level).