Colon carcinoma

Summary

Colon carcinoma (MONDO:0002032) is a cancer (an umbrella term covering 6 Mondo subtypes) with 66 cohort genes (97 GWAS associations across 19 studies; 44 CIViC-evidence somatic drivers; 872 ClinVar predisposition records) and 1,070 clinical trials. The dominant Reactome pathway is Diseases of DNA repair (8 cohort genes). Molecularly, KRAS G13D confers sensitivity to Cetuximab in Colon Cancer (CIViC Level B); 23 further subtype–drug associations are mapped below. Top therapeutic interventions include leucovorin, panitumumab, and tipiracil.

At a glance

• Classification: Cancer
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 66
• GWAS associations: 97
• ClinVar variants: 872
• Clinical trials: 1,070
• Precision-medicine evidence (CIViC): 24 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	colon carcinoma
Mondo ID	MONDO:0002032
EFO	EFO:1001950
DOID	DOID:1520
ICD-11	865099988
NCIT	C4910
SNOMED CT	269533000
UMLS	C0699790
MedGen	147065
Anatomy (UBERON)	UBERON:0001155
Is cancer (heuristic)	yes

Also known as: carcinoma of colon · carcinoma of the colon · colon cancer · colon carcinoma · colonic carcinoma

Data availability: 872 ClinVar variants · 97 GWAS associations (19 studies) · 2,131 cell lines.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › large intestine disorder › colonic disorder › colonic neoplasm › malignant colon neoplasm › colon carcinoma

Related subtypes (8): descending colon cancer, sigmoid colon cancer, cecum cancer, colon lymphoma, ascending colon cancer, transverse colon cancer, colon sarcoma, metastasis from malignant tumor of colon

Subtypes (6): colon adenocarcinoma, rectosigmoid carcinoma, colon small cell neuroendocrine carcinoma, colon carcinoma in situ, cecum carcinoma, squamous cell carcinoma of colon

Genetics & variants

GWAS landscape

97 GWAS associations across 19 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6983267	8e-26	PCAT1, CASC8, POU5F1B, CCAT2	G	0.15
chr8:128410948	1e-23		C	0.15
chr18:46453156	4e-19		?	0.18
rs7014346	4e-17	CASC8, PCAT1, POU5F1B	A	1.22
chr10:8734761	1e-16		?	0.15
rs73376930	9e-15	GREM1	A	0.13
rs6117251	7e-14	FGFR3P3 - CASC20	A	0.12
chr8:128421128	1e-13		?	0.15
chr5:134457675	2e-13		?	0.15
rs704017	2e-13	ZMIZ1-AS1	A	0.1
rs2293582	3e-13	GREM1, GREM1-AS1	G	0.14
rs11874392	4e-13	SMAD7	A	0.1
rs16892766	7e-13	LINC00536 - EIF3H	A	0.16
rs933698921	3e-12	CNTNAP2	G	1.32
rs827386	1e-11	RNA5SP299 - LINC02676	A	0.1
chr1:222148971	4e-11		?	0.12
chr20:7784672	4e-10		?	0.11
chr12:112468206	6e-10		?	0.15
rs7912831	6e-10	RNA5SP299 - LINC02676	?
chr10:114306441	9e-10		?	0.13
rs8114643	2e-09	SRSF10P2 - HSPBAP1P1	G	1.21
chr8:117632965	3e-09		?	0.1
rs78201730	6e-09	WIPF2	?	3.98
chr8:117715457	8e-09		?	0.21
rs12140498	9e-09	LINC01705	T	1.17
rs3124454	1e-08	CHORDC1P5 - CASP3P1	G	1.07
rs353548	1e-08	TWF2	G	1.15
rs71518872	1e-08	LINC03047 - ODF1	G	1.57
rs7601541	2e-08	RN7SL468P - STEAP3	?	6.78
rs736037	3e-08	FAM118A	A	1.07

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST012203	Huyghe JR	2021	32,002	64,159	Genetic architectures of proximal and distal colorectal cancer are partly distinct.
GCST90475567	Verma A	2024	9,125	438,096	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90011811	Rashkin SR	2020	3,793	410,350	Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
GCST90041807	Jiang L	2021	3,221	453,127	A generalized linear mixed model association tool for biobank-scale data.
GCST90435578	Zhou W	2018	3,051	382,756	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651289	Liu TY	2025	2,846	214,673	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90308765	Park HA	2022	2,547	0	Predictive polygenic score for outcome after first-line oxaliplatin-based chemotherapy in colorectal cancer patients using supervised principal component analysis.
GCST90477179	Verma A	2024	2,069	118,718	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479781	Verma A	2024	2,069	118,718	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90041895	Jiang L	2021	1,482	454,794	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	49

MAF distribution

Bucket	Variants
common (>=0.05)	27
low_freq (0.01-0.05)	5
rare (<0.01)	1
unknown	17

Functional consequences

Consequence	Count
intron_variant	25
unknown	14
intergenic_variant	8
non_coding_transcript_exon_variant	2
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6983267	8	127401060	G>T	0.41	non_coding_transcript_exon_variant	PCAT1, CASC8, POU5F1B, CCAT2	8e-26	Tier 4: intronic/intergenic
chr8:128410948				0.494			1e-23	Tier 4: intronic/intergenic
chr18:46453156							4e-19	Tier 4: intronic/intergenic
rs7014346	8	127412547	A>C,G	0.05	intron_variant	CASC8, PCAT1, POU5F1B	4e-17	Tier 4: intronic/intergenic
chr10:8734761							1e-16	Tier 4: intronic/intergenic
rs73376930	15	32720301	A>C,G	0.22	intron_variant	GREM1	9e-15	Tier 4: intronic/intergenic
rs6117251	20	6425793	A>G	0.307	intergenic_variant	FGFR3P3 - CASC20	7e-14	Tier 4: intronic/intergenic
chr8:128421128							1e-13	Tier 4: intronic/intergenic
chr5:134457675							2e-13	Tier 4: intronic/intergenic
rs704017	10	79059375	A>G	0.449	intron_variant	ZMIZ1-AS1	2e-13	Tier 4: intronic/intergenic
rs2293582	15	32718211	G>A,C,T	0.187	non_coding_transcript_exon_variant	GREM1, GREM1-AS1	3e-13	Tier 4: intronic/intergenic
rs11874392	18	48926786	A>G,T	0.472	intron_variant	SMAD7	4e-13	Tier 4: intronic/intergenic
rs16892766	8	116618444	A>C	0.085	regulatory_region_variant	LINC00536 - EIF3H	7e-13	Tier 3: regulatory
rs933698921	7	148081819	G>A,T	0.003	intron_variant	CNTNAP2	3e-12	Tier 4: intronic/intergenic
rs827386	10	8663948	A>C,T	0.292	intergenic_variant	RNA5SP299 - LINC02676	1e-11	Tier 4: intronic/intergenic
chr1:222148971							4e-11	Tier 4: intronic/intergenic
chr20:7784672							4e-10	Tier 4: intronic/intergenic
chr12:112468206							6e-10	Tier 4: intronic/intergenic
rs7912831	10	8689292	C>T	0.05	intergenic_variant	RNA5SP299 - LINC02676	6e-10	Tier 4: intronic/intergenic
chr10:114306441							9e-10	Tier 4: intronic/intergenic
rs8114643	20	7852399	A>G	0.136	intergenic_variant	SRSF10P2 - HSPBAP1P1	2e-09	Tier 4: intronic/intergenic
chr8:117632965							3e-09	Tier 4: intronic/intergenic
rs78201730	17	40276973	A>C,G,T	0.05	intron_variant	WIPF2	6e-09	Tier 4: intronic/intergenic
chr8:117715457							8e-09	Tier 4: intronic/intergenic
rs12140498	1	221925348	C>A,T	0.05	intron_variant	LINC01705	9e-09	Tier 4: intronic/intergenic
rs3124454	1	70574483	G>A,T	0.419	intron_variant	CHORDC1P5 - CASP3P1	1e-08	Tier 4: intronic/intergenic
rs353548	3	52235475	A>C,G,T	0.047	intron_variant	TWF2	1e-08	Tier 4: intronic/intergenic
rs71518872	8	102549750	C>G	0.015	intron_variant	LINC03047 - ODF1	1e-08	Tier 4: intronic/intergenic
rs7601541	2	119184520	C>G	0.05	intron_variant	RN7SL468P - STEAP3	2e-08	Tier 4: intronic/intergenic
rs736037	22	45329118	G>A,C	0.286	intron_variant	FAM118A	3e-08	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

160 pathogenic, 136 conflicting classifications of pathogenicity, 87 uncertain significance, 73 benign/likely benign, 54 benign, 41 pathogenic/likely pathogenic, 19 likely benign, 17 likely pathogenic, 9 not provided, 3 association, 1 pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
13983	NM_001382430.1(AKT1):c.49G>A (p.Glu17Lys)	AKT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1049076	NM_000038.6(APC):c.-2_136-2903del	APC	Pathogenic	no assertion criteria provided
1049077	NM_000038.6(APC):c.2893_2896del (p.Asn965fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
1049497	NM_000038.6(APC):c.1744-2_1958+1del	APC	Pathogenic	no assertion criteria provided
1049574	NM_000038.6(APC):c.1259_1269del (p.Cys420fs)	APC	Pathogenic	no assertion criteria provided
1049772	NM_000038.6(APC):c.1409-2del	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1049778	NM_000038.6(APC):c.-2_135+1824del	APC	Pathogenic	no assertion criteria provided
1049811	NM_000038.6(APC):c.194del (p.Gln65fs)	APC	Pathogenic	no assertion criteria provided
1049899	NM_000038.6(APC):c.423-3_531+198del	APC	Pathogenic	no assertion criteria provided
1050133	NM_000038.6(APC):c.1046_1140del (p.Gln349fs)	APC	Pathogenic	no assertion criteria provided
1050316	NM_000038.6(APC):c.2928_2929del (p.Gly977fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
1050389	NM_000038.6(APC):c.2487del (p.Val830fs)	APC	Pathogenic	no assertion criteria provided
1050412	NM_001127511.3(APC):c.166-28469_166-27547del	APC	Pathogenic	no assertion criteria provided
1050449	NM_000038.6(APC):c.3847del (p.Ala1283fs)	APC	Pathogenic	no assertion criteria provided
1050476	NM_000038.6(APC):c.3026del (p.His1009fs)	APC	Pathogenic	no assertion criteria provided
1050611	NM_000038.6(APC):c.1313-2_1743+144del	APC	Pathogenic	no assertion criteria provided
1050614	NM_000038.6(APC):c.4164_4165del (p.Ser1389fs)	APC	Pathogenic	no assertion criteria provided
1050689	NM_000038.6(APC):c.3079del (p.Tyr1027fs)	APC	Pathogenic	no assertion criteria provided
1050722	NM_000038.6(APC):c.604del (p.Glu202fs)	APC	Pathogenic	no assertion criteria provided
127312	NM_000038.6(APC):c.646C>T (p.Arg216Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
140952	NM_000038.6(APC):c.637C>T (p.Arg213Ter)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141368	NM_000038.6(APC):c.147_150del (p.Lys49fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
141515	NM_000038.6(APC):c.220+2T>A	APC	Pathogenic	reviewed by expert panel
142574	NM_000038.6(APC):c.426_427del (p.Leu143fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
156482	NM_000038.6(APC):c.1744-2A>G	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
184999	NM_000038.6(APC):c.847C>T (p.Arg283Ter)	APC	Pathogenic	reviewed by expert panel
216014	NM_000038.6(APC):c.2626C>T (p.Arg876Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
216017	NM_000038.6(APC):c.423G>T (p.Arg141Ser)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
216848	NM_000038.6(APC):c.453del (p.Glu152fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
217923	NM_000038.6(APC):c.1312+1G>A	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 234 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66
ZEB1	Act	GBM,LUAD,LUSC,NPC,PCM,SCLC	CIViC #5649
BIRC7			CIViC #14842
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
POU5F1			CIViC #4419
BMPR1A	LoF	STAD
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
EPCAM			CIViC #3364
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
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888
BRIP1			CIViC #15955
CTNNB1	Act	ACC,COAD,COADREAD,ESCA,HCC,LIHB,LUAD,MBL,MEL,NSCLC,OVT,PAST,PRAD,PROSTATE,RMS,SKIN,SOFT_TISSUE,STAD,UCEC,WT	CIViC #1290
PALB2	LoF	OVT	CIViC #15013
DCC	LoF	COADREAD,ESCA,HCC,PAAD,PRAD	CIViC #1396
FLCN	LoF	LUAD	CIViC #19959
EP300	LoF	ANGS,BLCA,BRCA,CESC,CHOL,COADREAD,DLBCLNOS,ESCA,HCC,HNSC,LUAD,LUSC,MBL,MLYM,NHL,NPC,SCLC,STOMACH,UTUC	CIViC #1704
FANCC			CIViC #1811
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
FLT4	LoF	ANGS,BCC,BLCA,CCRCC,CHRCC,HCC,LUAD,LUSC,NBL,UCEC	CIViC #1938
AKT1	Act	ALL,BRCA,CESC,COADREAD,PRAD,PROSTATE,SARCNOS,UCEC,WDTC	CIViC #2
KDR	Act	ANGS,BRCA,CLLSLL,DLBCLNOS,LUAD,PANCREAS,SKIN	CIViC #3153
SMAD4	LoF	BRCA,CESC,CHOL,COAD,COADREAD,ESCA,ESCC,GBC,HNSC,LUAD,NSCLC,PAAD,PANCREAS,PRAD,PROSTATE,READ,STAD,STOMACH	CIViC #77
MLH1			CIViC #3532
MSH2			CIViC #3628
MSH6			CIViC #2478

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach
APC	Orphanet:3258	Cenani-Lenz syndrome
APC	Orphanet:873	Desmoid tumor
ZEB1	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98974	Fuchs endothelial corneal dystrophy
ERBB2	Orphanet:213726	Serous carcinoma of the corpus uteri
ERBB2	Orphanet:2800	Extramammary Paget disease
ERBB2	Orphanet:388	Hirschsprung disease
ERBB2	Orphanet:99976	Adenocarcinoma of the oesophagus and oesophagogastric junction
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
BMPR1A	Orphanet:157794	Hereditary mixed polyposis syndrome
BMPR1A	Orphanet:329971	Generalized juvenile polyposis/juvenile polyposis coli
BMPR1A	Orphanet:440437	Familial colorectal cancer Type X
BMPR1A	Orphanet:79076	Juvenile polyposis of infancy
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

Cohort genes → proteins

66 cohort genes, 66 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	6
civic_only	5
multi_evidence	55

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar,civic_evidence
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar,civic_evidence
ZEB1	HGNC:11642	ENSG00000148516	P37275	Zinc finger E-box-binding homeobox 1	civic_evidence
BIRC7	HGNC:13702	ENSG00000101197	Q96CA5	Baculoviral IAP repeat-containing protein 7	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
POU5F1	HGNC:9221	ENSG00000204531	Q01860	POU domain, class 5, transcription factor 1	civic_evidence
BMPR1A	HGNC:1076	ENSG00000107779	P36894	Bone morphogenetic protein receptor type-1A	clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
BUB1	HGNC:1148	ENSG00000169679	O43683	Mitotic checkpoint serine/threonine-protein kinase BUB1	clinvar
BUB1B	HGNC:1149	ENSG00000156970	O60566	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	clinvar
EPCAM	HGNC:11529	ENSG00000119888	P16422	Epithelial cell adhesion molecule	clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
SIRAL2	HGNC:1313	ENSG00000100376	Q9NWS6	Protein FAM118A	gwas
TLR9	HGNC:15633	ENSG00000239732	Q9NR96	Toll-like receptor 9	gwas
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
RAD54B	HGNC:17228	ENSG00000197275	Q9Y620	DNA repair and recombination protein RAD54B	clinvar
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar
NISCH	HGNC:18006	ENSG00000010322	Q9Y2I1	Nischarin	gwas
STAB1	HGNC:18628	ENSG00000010327	Q9NY15	Stabilin-1	gwas
BRIP1	HGNC:20473	ENSG00000136492	Q9BX63	Fanconi anemia group J protein	clinvar
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	clinvar
FLCN	HGNC:27310	ENSG00000154803	Q8NFG4	Folliculin	clinvar
C11orf65	HGNC:28519	ENSG00000166323	Q8NCR3	Protein MFI	clinvar
DLC1	HGNC:2897	ENSG00000164741	Q96QB1	Rho GTPase-activating protein 7	clinvar
EP300	HGNC:3373	ENSG00000100393	Q09472	Histone acetyltransferase p300	clinvar
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	clinvar
FANCE	HGNC:3586	ENSG00000112039	Q9HB96	Fanconi anemia group E protein	clinvar
FBLN1	HGNC:3600	ENSG00000077942	P23142	Fibulin-1	gwas
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar
FLT1	HGNC:3763	ENSG00000102755	P17948	Vascular endothelial growth factor receptor 1	clinvar
FLT4	HGNC:3767	ENSG00000037280	P35916	Vascular endothelial growth factor receptor 3	clinvar
AKT1	HGNC:391	ENSG00000142208	P31749	RAC-alpha serine/threonine-protein kinase	clinvar
KDR	HGNC:6307	ENSG00000128052	P35968	Vascular endothelial growth factor receptor 2	clinvar
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	clinvar
MCC	HGNC:6935	ENSG00000171444	P23508	Colorectal mutant cancer protein	clinvar
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	clinvar
MLH3	HGNC:7128	ENSG00000119684	Q9UHC1	DNA mismatch repair protein Mlh3	clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	clinvar
MT-ND1	HGNC:7455	ENSG00000198888	P03886	NADH-ubiquinone oxidoreductase chain 1	clinvar
MUTYH	HGNC:7527	ENSG00000132781	Q9UIF7	Adenine DNA glycosylase	clinvar
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	clinvar
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
APC	Adenomatous polyposis coli protein	Tumor suppressor.
ZEB1	Zinc finger E-box-binding homeobox 1	Acts as a transcriptional repressor.
BIRC7	Baculoviral IAP repeat-containing protein 7	Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control.
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.
POU5F1	POU domain, class 5, transcription factor 1	Transcription factor that binds to the octamer motif (5’-ATTTGCAT-3’).
BMPR1A	Bone morphogenetic protein receptor type-1A	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
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…
BUB1	Mitotic checkpoint serine/threonine-protein kinase BUB1	Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment.
BUB1B	Mitotic checkpoint serine/threonine-protein kinase BUB1 beta	Essential component of the mitotic checkpoint.
EPCAM	Epithelial cell adhesion molecule	May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosa…
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TLR9	Toll-like receptor 9	Key component of innate and adaptive immunity.
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.
RAD54B	DNA repair and recombination protein RAD54B	Multifunctional ATPase that could play with RAD54, a redundant role in homologous recombination (HR), a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication for…
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.
NISCH	Nischarin	Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling.
STAB1	Stabilin-1	Acts as a scavenger receptor for acetylated low density lipoprotein.
BRIP1	Fanconi anemia group J protein	DNA-dependent ATPase and 5’-3’ DNA helicase required for the maintenance of chromosomal stability.
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.
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.
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
FLCN	Folliculin	Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis.
C11orf65	Protein MFI	Acts as an inhibitor of mitochondrial fission.
DLC1	Rho GTPase-activating protein 7	Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling.
EP300	Histone acetyltransferase p300	Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling.
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
FANCE	Fanconi anemia group E protein	As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair.
FBLN1	Fibulin-1	Incorporated into fibronectin-containing matrix fibers.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
FLT1	Vascular endothelial growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage funct…
FLT4	Vascular endothelial growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic developm…
AKT1	RAC-alpha serine/threonine-protein kinase	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
KDR	Vascular endothelial growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
MCC	Colorectal mutant cancer protein	Candidate for the putative colorectal tumor suppressor gene located at 5q21.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
MLH3	DNA mismatch repair protein Mlh3	Probably involved in the repair of mismatches in DNA.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).
MT-ND1	NADH-ubiquinone oxidoreductase chain 1	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.
MUTYH	Adenine DNA glycosylase	Involved in oxidative DNA damage repair.
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.
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.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

Protein-family classification

Druggable: 27 · Difficult: 12 · Unknown: 27 · Druggable fraction: 0.41

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	15	6.3×	1e-07
Phosphatase	3	3.8×	0.221
Nuclear receptor	1	5.8×	0.525
Complement	1	4.1×	0.547
Transcription factor	10	1.2×	0.548
Antibody/Immunoglobulin	2	0.9×	0.995
Other/Unknown	27	0.7×	0.995
Enzyme (other)	4	0.7×	0.995
Scaffold/PPI	2	0.5×	0.995
GPCR	1	0.4×	0.995

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
ZEB1	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
BIRC7	Transcription factor	no		BIR_rpt, Znf_RING, Znf_RING/FYVE/PHD
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
POU5F1	Transcription factor	no		POU_dom, HD, Homeodomain-like_sf
BMPR1A	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_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
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BUB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BUB1B	Kinase	yes	2.7.11.1	Kinase-like_dom_sf, Mad3/Bub1_I, Bub1/Mad3
EPCAM	Enzyme (other)	yes	2.4.1.37	Thyroglobulin_1, Thyroglobulin_1_sf, EpCAM_N
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
SIRAL2	Other/Unknown	no		FAM118
TLR9	Other/Unknown	no		TIR_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
RAD54B	Enzyme (other)	yes	3.6.4.B9	SNF2_N, Helicase_C-like, Helicase_ATP-bd
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
NISCH	Other/Unknown	no		Leu-rich_rpt, PX_dom, LRR_dom_sf
STAB1	Other/Unknown	no		Link_dom, EGF, FAS1_domain
BRIP1	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
FLCN	Other/Unknown	no		Folliculin, Folliculin_DENN, Folliculin/SMCR8_longin
C11orf65	Other/Unknown	no
DLC1	Other/Unknown	no		RhoGAP_dom, SAM, START_lipid-bd_dom
EP300	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
FANCC	Other/Unknown	no		FANCC
FANCE	Other/Unknown	no		Fanconi_anaemia_gr_E_prot_C, FANCE
FBLN1	Complement	yes		Anaphylatoxin/fibulin, EGF-type_Asp/Asn_hydroxyl_site, EGF
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FLT1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
FLT4	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
AKT1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
KDR	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
MCC	Scaffold/PPI	no		USHBP1_PDZ-bd, USBP1-like
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MLH3	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N
MT-ND1	Other/Unknown	no		NADH_UbQ_OxRdtase_su1/FPO, NADH_UbQ_OxRdtase_su1_CS
MUTYH	Other/Unknown	no		NUDIX_hydrolase_dom, HhH_motif, HhH-GPD_domain
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS

Expression context

Cohort genes with no expression data: 0.

64 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)	66
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	11
primordial germ cell in gonad	9
calcaneal tendon	8
secondary oocyte	8
male germ line stem cell (sensu Vertebrata) in testis	8
right testis	6
colonic epithelium	5
adrenal tissue	5
ganglionic eminence	5
oocyte	5
buccal mucosa cell	4
sural nerve	4
left testis	4
cerebellar hemisphere	4
right hemisphere of cerebellum	4
right uterine tube	3
gingival epithelium	3
pericardium	3
monocyte	3
tendon	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus
ZEB1	287	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
BIRC7	109	tissue_specific	marker	adrenal tissue, tibial nerve, sural nerve
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
POU5F1	132	tissue_specific	marker	primordial germ cell in gonad, right uterine tube, metanephros cortex
BMPR1A	284	ubiquitous	marker	secondary oocyte, calcaneal tendon, saphenous vein
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
BUB1	185	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, ganglionic eminence
BUB1B	210	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
EPCAM	253	broad	marker	jejunal mucosa, colonic mucosa, mucosa of sigmoid colon
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
SIRAL2	239	ubiquitous	marker	right testis, left testis, gall bladder
TLR9	119	tissue_specific	marker	blood, granulocyte, lymph node
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
RAD54B	201	ubiquitous	yes	right uterine tube, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium
NISCH	293	ubiquitous	marker	middle temporal gyrus, right hemisphere of cerebellum, cerebellar hemisphere
STAB1	233	broad	marker	spleen, right adrenal gland cortex, right adrenal gland
BRIP1	181	ubiquitous	marker	ventricular zone, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
DCC	154	broad	marker	cortical plate, right testis, left testis
FLCN	261	ubiquitous	marker	buccal mucosa cell, right hemisphere of cerebellum, cerebellar hemisphere
C11orf65	163	ubiquitous	marker	sperm, left testis, right testis
DLC1	268	ubiquitous	marker	adrenal tissue, lower lobe of lung, sural nerve
EP300	292	ubiquitous	marker	colonic epithelium, adrenal tissue, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 170.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
AKT1	16,601
CTNNB1	15,668
KRAS	14,509
PTEN	11,626
EP300	10,122
ERBB2	9,659
BRCA1	9,064
CDH1	8,738
PPARG	7,747

Intra-cohort edges

A	B	Sources
AKT1	ATM	intact
AKT1	DLC1	string_interaction
AKT1	FANCC	intact
AKT1	FANCE	intact
AKT1	MLH3	biogrid_interaction, intact
AKT1	MUTYH	intact
AKT1	PIK3CA	biogrid_interaction, string_interaction
AKT1	PTEN	string_interaction
APC	AXIN2	string_interaction
APC	CTNNB1	intact, string_interaction
ATM	BARD1	string_interaction
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CHEK2	string_interaction
ATM	MLH1	string_interaction
ATM	MSH2	string_interaction
ATM	MSH6	string_interaction
ATM	NBN	biogrid_interaction, string_interaction
ATM	STK11	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
ATM	ZEB1	biogrid_interaction
AXIN2	BARD1	intact
AXIN2	CTNNB1	intact, string_interaction
AXIN2	SMAD4	intact
BARD1	BRCA1	biogrid_interaction, intact, string_interaction
BARD1	BRCA2	string_interaction
BARD1	BRIP1	biogrid_interaction
BARD1	CHEK2	string_interaction
BARD1	PALB2	string_interaction
BARD1	RAD51C	string_interaction
BMPR1A	SMAD4	string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MLH1	string_interaction
BRAF	NRAS	biogrid_interaction, intact, string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	PMS2	string_interaction
BRAF	POLE	intact
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	BRIP1	biogrid_interaction, intact, string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	FANCE	intact, string_interaction
BRCA1	MLH1	string_interaction
BRCA1	MSH2	string_interaction
BRCA1	MSH6	string_interaction
BRCA1	NBN	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	PMS2	string_interaction

Structural data

PDB: 60 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
PPARG	P37231	380
TP53	P04637	313
PIK3CA	P42336	135
BRAF	P15056	131
ERBB2	P04626	63
EP300	Q09472	60
KDR	P35968	54
CTNNB1	P35222	50
AKT1	P31749	43
CHEK2	O96017	38
BAX	Q07812	37
NRAS	P01111	35
BRCA1	P38398	33
APC	P25054	31
MSH2	P43246	30
CDH1	P12830	22
POLE	Q07864	18
RAD51C	O43502	17
POU5F1	Q01860	16
FGFR3	P22607	15
PDGFRA	P16234	15
BRCA2	P51587	14
ATM	Q13315	14
REV3L	O60673	14
BIRC7	Q96CA5	13
FLT1	P17948	12
SMAD4	Q13485	12
PTEN	P60484	12
BMPR1A	P36894	11

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SIRAL2	Q9NWS6	83.77
PDGFRL	Q15198	83.54
FBLN1	P23142	79.49
C11orf65	Q8NCR3	74.69
STAB1	Q9NY15	68.00
MLH3	Q9UHC1	56.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 648. Enrichment computed across 66 evidence-associated genes (61 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 61 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Diseases of DNA repair	8	74.9×	3e-11	BRCA1, BRCA2, MLH1, MSH2, MSH6, NBN, ATM, BARD1
Impaired BRCA2 binding to PALB2	8	59.9×	9e-11	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, BARD1, RAD51C
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	8	55.5×	9e-11	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, BARD1, RAD51C
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	8	55.5×	9e-11	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, BARD1, RAD51C
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	8	55.5×	9e-11	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, BARD1, RAD51C
HDR through Homologous Recombination (HRR)	10	31.2×	9e-11	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, POLD1, POLE (+2 more)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	8	51.6×	1e-10	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, BARD1, RAD51C
Homologous DNA Pairing and Strand Exchange	8	49.9×	2e-10	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, BARD1, RAD51C
Resolution of D-loop Structures through Holliday Junction Intermediates	8	39.4×	1e-09	BRCA1, BRCA2, BRIP1, PALB2, NBN, ATM, BARD1, RAD51C
Presynaptic phase of homologous DNA pairing and strand exchange	7	31.2×	1e-07	BRCA1, BRCA2, BRIP1, NBN, ATM, BARD1, RAD51C
Defective homologous recombination repair (HRR) due to PALB2 loss of function	5	78.0×	2e-07	BRCA1, BRCA2, NBN, ATM, BARD1
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	5	66.9×	3e-07	MLH1, MSH2, MSH6, PMS2, POLD1
Diseases of DNA Double-Strand Break Repair	5	66.9×	3e-07	BRCA1, BRCA2, NBN, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	5	66.9×	3e-07	BRCA1, BRCA2, NBN, ATM, BARD1
Resolution of D-Loop Structures	5	52.0×	1e-06	BRCA1, BRCA2, NBN, ATM, BARD1
Impaired BRCA2 binding to RAD51	6	30.4×	1e-06	BRCA1, BRCA2, BRIP1, NBN, ATM, BARD1
TP53 Regulates Transcription of DNA Repair Genes	7	20.8×	1e-06	BRCA1, TP53, FANCC, MLH1, MSH2, ATM, PMS2
Regulation of TP53 Activity through Phosphorylation	8	15.4×	1e-06	BRCA1, STK11, TP53, CHEK2, BRIP1, NBN, ATM, BARD1
Meiosis	6	28.1×	2e-06	BRCA1, BRCA2, MLH1, MLH3, NBN, ATM
DNA Repair	8	12.9×	5e-06	BRCA1, BRCA2, MLH1, MSH2, MSH6, NBN, ATM, BARD1
Constitutive Signaling by Overexpressed ERBB2	4	62.4×	1e-05	ERBB2, KRAS, NRAS, PTPN12
Meiotic recombination	7	14.9×	1e-05	BRCA1, BRCA2, MLH1, MLH3, NBN, ATM, RAD51C
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	4	57.6×	1e-05	KRAS, NRAS, PDGFRA, PIK3CA
Signaling by PDGFRA extracellular domain mutants	4	57.6×	1e-05	KRAS, NRAS, PDGFRA, PIK3CA
Transcriptional Regulation by TP53	9	9.2×	1e-05	BRCA1, STK11, AKT1, MLH1, MSH2, NBN, ATM, BARD1 (+1 more)
Mismatch Repair	3	140.4×	1e-05	MLH1, MSH2, MSH6
Diseases of Mismatch Repair (MMR)	3	140.4×	1e-05	MLH1, MSH2, MSH6
G2/M DNA damage checkpoint	7	13.8×	2e-05	BRCA1, TP53, CHEK2, BRIP1, NBN, ATM, BARD1
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	4	53.5×	2e-05	MLH1, MSH2, PMS2, POLD1
Reproduction	6	18.7×	2e-05	BRCA1, BRCA2, MLH1, MLH3, NBN, ATM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 64 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
homologous recombination	5	109.7×	3e-07	BRCA1, RAD54B, BRIP1, NBN, BARD1
mismatch repair	6	60.8×	3e-07	MLH1, MLH3, MSH2, MSH6, MUTYH, PMS2
double-strand break repair	8	25.4×	4e-07	BRCA1, BRCA2, TP53, CHEK2, BRIP1, MSH2, NBN, ATM
double-strand break repair via homologous recombination	8	19.5×	2e-06	BRCA1, BRCA2, RAD54B, PALB2, NBN, ATM, RAD51C, REV3L
protein autophosphorylation	8	18.2×	3e-06	STK11, CHEK2, FLT1, FLT4, AKT1, KDR, ATM, PDGFRA
somitogenesis	6	35.1×	4e-06	BMPR1A, TP53, PALB2, EP300, ATM, AXIN2
intrinsic apoptotic signaling pathway in response to DNA damage	6	30.4×	7e-06	BRCA1, CHEK2, MLH1, MSH6, ATM, BAX
positive regulation of gene expression	12	7.3×	1e-05	BRAF, BMPR1A, BRCA1, TP53, TLR9, CTNNB1, FBLN1, AKT1 (+4 more)
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	5	38.7×	2e-05	BRCA2, TP53, CHEK2, EP300, MSH2
somatic recombination of immunoglobulin gene segments	3	197.5×	3e-05	MSH2, MSH6, PMS2
somatic hypermutation of immunoglobulin genes	4	65.8×	4e-05	MLH1, MSH2, MSH6, PMS2
determination of adult lifespan	5	33.8×	4e-05	TP53, RAD54B, MSH2, MSH6, ATM
peptidyl-tyrosine phosphorylation	5	32.9×	4e-05	ERBB2, FLT1, FLT4, KDR, PDGFRA
cellular response to indole-3-methanol	3	158.0×	5e-05	BRCA1, CDH1, CTNNB1
ovarian follicle development	5	30.6×	5e-05	FANCE, KDR, SMAD4, ATM, BAX
regulation of signal transduction by p53 class mediator	5	29.9×	5e-05	STK11, CHEK2, EP300, AKT1, ATM
DNA repair	9	9.0×	5e-05	BRCA1, BRIP1, FANCC, MSH2, MSH6, MUTYH, POLD1, BARD1 (+1 more)
isotype switching	4	52.7×	6e-05	MLH1, MSH2, MSH6, NBN
DNA damage response, signal transduction by p53 class mediator	5	28.0×	6e-05	BRCA2, TP53, CHEK2, NBN, ATM
intrinsic apoptotic signaling pathway	5	28.0×	6e-05	TP53, FLCN, MSH6, NBN, BAX
positive regulation of isotype switching to IgA isotypes	3	131.7×	6e-05	MLH1, MSH2, PMS2
positive regulation of MAPK cascade	8	10.1×	7e-05	TLR9, CTNNB1, ERBB2, FGFR3, FLT1, FLT4, KDR, PTPRJ
regulation of cell cycle	8	9.3×	1e-04	BRCA1, STK11, TP53, BIRC7, NBN, ATM, BARD1, BAX
DNA strand resection involved in replication fork processing	3	98.7×	2e-04	BRCA1, NBN, BARD1
MAPK cascade	6	14.4×	2e-04	BRAF, BMPR1A, CTNNB1, FGFR3, KRAS, NRAS
mitotic spindle assembly checkpoint signaling	4	35.1×	2e-04	APC, BUB1, BUB1B, ATM
reciprocal meiotic recombination	4	35.1×	2e-04	RAD54B, MLH3, ATM, RAD51C
cellular response to vascular endothelial growth factor stimulus	4	35.1×	2e-04	FLT1, FLT4, AKT1, KDR
epidermal growth factor receptor signaling pathway	5	19.4×	3e-04	BRAF, CTNNB1, ERBB2, AKT1, PIK3CA
positive regulation of transforming growth factor beta receptor signaling pathway	4	32.9×	3e-04	STK11, FLCN, EP300, SMAD4

Therapeutics

Drugs indicated for this disease

1 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Capecitabine	Approved (phase 4)
Celecoxib	Phase 3 (in late-stage trials)
Cetuximab	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ipilimumab, Nivolumab, Palbociclib, Relatlimab, Tecemotide, Tipiracil, Trastuzumab, Trifluridine, Tucatinib.

Drug target analysis

Approved (phase 4): 24 · Phase ≥3: 25 · Phased (≥1): 29 · Undrugged: 37

Druggability breadth: 44 of 66 evidence-associated genes (67%) 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
BRAF	VEMURAFENIB
ERBB2	CLOTRIMAZOLE
KRAS	VEMURAFENIB
POU5F1	FAMOTIDINE
BMPR1A	MOMELOTINIB
BRCA1	RIBOFLAVIN
STK11	FEDRATINIB
BUB1	GILTERITINIB
BUB1B	CERITINIB
TP53	NITROFURANTOIN
TLR9	HYDROXYCHLOROQUINE
CHEK2	NERATINIB
NISCH	TIZANIDINE
CTNNB1	DITHIAZANINE IODIDE
FGFR3	PONATINIB
FLT1	PONATINIB
FLT4	FEDRATINIB
AKT1	CAPIVASERTIB
KDR	VANDETANIB
ATM	AMIODARONE HYDROCHLORIDE
PDGFRA	PONATINIB
PIK3CA	IDELALISIB
PPARG	METHYLENE BLUE ANHYDROUS
PTGER3	LAROPIPRANT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
KDR	172	4
ERBB2	83	4
PPARG	83	4
FLT1	77	4
PDGFRA	77	4
FLT4	72	4
PIK3CA	67	4
FGFR3	64	4
BRAF	48	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF, KDR, KRAS
PONATINIB	4	BRAF, ERBB2, FGFR3, FLT1, KDR, PDGFRA
FEDRATINIB	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
SORAFENIB	4	BRAF, ERBB2, FGFR3, FLT1, FLT4, KDR
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
INFIGRATINIB	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
REGORAFENIB	4	BRAF, FLT1, FLT4, KDR, PDGFRA
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, PDGFRA
ABEMACICLIB	4	BRAF, KDR
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
DASATINIB	4	BMPR1A, BRAF, ERBB2, FGFR3, FLT1, KDR
ERLOTINIB	4	BRAF, BUB1, ERBB2, FLT1, FLT4, KDR
GEFITINIB	4	BRAF, CHEK2, ERBB2, FLT4, KDR
IMATINIB	4	BRAF, ERBB2, KDR, PDGFRA
CLOTRIMAZOLE	4	ERBB2, TP53
ERLOTINIB HYDROCHLORIDE	4	ERBB2
AFATINIB	4	ERBB2
LAPATINIB DITOSYLATE	4	ERBB2
NERATINIB	4	CHEK2, ERBB2, KDR
IBRUTINIB	4	ERBB2, KDR
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2, FLT1, FLT4, KDR
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 27.

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

Symbol	Assays	Type breakdown
KDR	2,687	Binding:2594, Functional:64, ADMET:27, Toxicity:2
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
PPARG	2,033	Binding:1593, Functional:380, ADMET:56, Toxicity:3, Unclassified:1
AKT1	1,942	Binding:1900, Functional:34, ADMET:7, Toxicity:1
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
FGFR3	975	Binding:948, Functional:18, ADMET:9
FLT1	896	Binding:852, Functional:38, ADMET:6
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
EP300	767	Binding:763, Functional:3, ADMET:1
FLT4	717	Binding:683, Functional:32, ADMET:2
CHEK2	690	Binding:687, Functional:2, ADMET:1
CTNNB1	361	Binding:358, Functional:3
STK11	244	Binding:244
ATM	240	Binding:233, Functional:5, ADMET:2
PTGER3	194	Binding:140, Functional:51, ADMET:3
BMPR1A	169	Binding:166, ADMET:3
TLR9	132	Binding:125, Functional:7
BUB1	86	Binding:84, Functional:2
BAX	49	Binding:47, Functional:2
NISCH	38	Binding:38
POU5F1	36	Binding:36
APC	24	Binding:24
CDH1	18	Binding:18
NRAS	18	Binding:18
PTPN12	18	Binding:13, ADMET:4, Functional:1
BIRC7	14	Binding:13, Functional:1
AXIN2	14	Binding:14
BRCA1	13	Binding:9, Functional:4
BUB1B	12	Binding:12
MSH6	10	Binding:10
MSH2	9	Binding:9
POLD1	8	Binding:8
PTEN	8	Binding:8
SMAD4	6	Binding:6
MT-ND1	5	Binding:5
PTPRJ	5	Binding:4, ADMET:1
NBN	2	Binding:2
EPCAM	1	Binding:1
MUTYH	1	Functional:1
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
BMPR1A	2.7.10.2	non-specific protein-tyrosine kinase
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
BUB1	2.7.11.1	non-specific serine/threonine protein kinase
BUB1B	2.7.11.1	non-specific serine/threonine protein kinase
EPCAM	2.4.1.37, 2.4.1.40	fucosylgalactoside 3-alpha-galactosyltransferase, glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
RAD54B	3.6.4.B9
BRIP1	3.6.4.12	DNA helicase
EP300	2.3.1.48	histone acetyltransferase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
FLT1	2.7.10.1	receptor protein-tyrosine kinase
FLT4	2.7.10.1	receptor protein-tyrosine kinase
AKT1	2.7.11.1	non-specific serine/threonine protein kinase
KDR	2.7.10.1	receptor protein-tyrosine kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
POLD1	2.7.7.7	DNA-directed DNA polymerase
POLE	2.7.7.7	DNA-directed DNA polymerase
BARD1	2.3.2.27	RING-type E3 ubiquitin transferase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
PTPN12	3.1.3.16, 3.1.3.48	protein-serine/threonine phosphatase, protein-tyrosine-phosphatase
PTPRJ	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRAF	1,442
ERBB2	1,221
KRAS	861
BMPR1A	169
STK11	244
TP53	869
TLR9	132
CHEK2	690
CTNNB1	361
EP300	767
FGFR3	975
FLT1	896
FLT4	717
AKT1	1,942
KDR	2,687
ATM	240
PDGFRA	1,172
PIK3CA	2,034
PPARG	2,033
PTGER3	194

Pharmacogenomics

Cohort genes with a PharmGKB record: 66; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

27 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)
VEMURAFENIB	4	BRAF, KDR, KRAS
PONATINIB	4	BRAF, ERBB2, FGFR3, FLT1, KDR, PDGFRA
FEDRATINIB	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
SORAFENIB	4	BRAF, ERBB2, FGFR3, FLT1, FLT4, KDR
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
INFIGRATINIB	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
REGORAFENIB	4	BRAF, FLT1, FLT4, KDR, PDGFRA
DABRAFENIB	4	BRAF, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF, PDGFRA
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF, FGFR3, FLT1, FLT4, KDR, PDGFRA
DASATINIB	4	BMPR1A, BRAF, ERBB2, FGFR3, FLT1, KDR
ERLOTINIB	4	BRAF, BUB1, ERBB2, FLT1, FLT4, KDR
GEFITINIB	4	BRAF, CHEK2, ERBB2, FLT4, KDR
IMATINIB	4	BRAF, ERBB2, KDR, PDGFRA
CLOTRIMAZOLE	4	ERBB2, TP53
AFATINIB	4	ERBB2
LAPATINIB DITOSYLATE	4	ERBB2
NERATINIB	4	CHEK2, ERBB2, KDR
IBRUTINIB	4	ERBB2, KDR
AFATINIB DIMALEATE	4	ERBB2
CABOZANTINIB	4	ERBB2, FLT1, FLT4, KDR
DACOMITINIB	4	ERBB2
DACOMITINIB ANHYDROUS	4	ERBB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	24	BRAF, ERBB2, KRAS, POU5F1, BMPR1A, BRCA1, STK11, BUB1, BUB1B, TP53 (+14 more)
B	Phased (≥1) drug, not yet approved	5	BIRC7, EP300, MSH6, NRAS, BAX
C	Druggable family + PDB, no drug	7	EPCAM, RAD54B, BRIP1, DCC, PTEN, PTPN12, PTPRJ
D	Druggable family + AlphaFold only, no drug	2	FBLN1, PDGFRL
E	Difficult family or no structure, no drug	28	APC, ZEB1, BRCA2, SIRAL2, CDH1, STAB1, PALB2, FLCN, C11orf65, DLC1 (+18 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
APC	24	CTNNB1
BRCA2	0	BRCA1
EPCAM	1	ERBB2
RAD54B	0	BRCA1
CDH1	18	CTNNB1
BRIP1	0	BRCA1
PALB2	0	BRCA1
SMAD4	6	CTNNB1
MLH1	0	MSH6
MLH3	0	AKT1
MUTYH	1	MSH6
NBN	2	ATM, BRCA1
AXIN2	14	CTNNB1
PMS2	1	MSH6
POLE	0	MSH6
PTEN	8	STK11, TP53, AKT1
ZEB1	0	—
SIRAL2	0	—
STAB1	0	—
DCC	0	—
FLCN	0	—
C11orf65	0	—
DLC1	0	—
FANCC	0	—
FANCE	0	—
FBLN1	0	—
MCC	0	—
MSH2	9	—
MT-ND1	5	—
PDGFRL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,070.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	585
PHASE2	176
PHASE1	120
PHASE3	75
PHASE1/PHASE2	73
EARLY_PHASE1	16
PHASE4	14
PHASE2/PHASE3	11

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05250648	PHASE4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT01169220	PHASE4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	PHASE4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	PHASE4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	PHASE4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	PHASE4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	PHASE4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	PHASE4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	PHASE4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	PHASE4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	PHASE4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	PHASE4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	PHASE4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT00217737	PHASE3	ACTIVE_NOT_RECRUITING	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT01460589	PHASE3	ACTIVE_NOT_RECRUITING	Early Commencement of Adjuvant Chemotherapy for Colon Cancer
NCT01918527	PHASE3	ACTIVE_NOT_RECRUITING	Neoadjuvant Chemotherapy Versus Standard Treatment in Patients With Locally Advanced Colon Cancer
NCT02301286	PHASE3	ACTIVE_NOT_RECRUITING	A Trial of Aspirin on Recurrence and Survival in Colon Cancer Patients
NCT02448173	PHASE3	NOT_YET_RECRUITING	A Multicenter Study of Active Specific Immunotherapy With OncoVax® in Patients With Stage II Colon Cancer
NCT02572141	PHASE3	ACTIVE_NOT_RECRUITING	FOLFOX or CAPOX Perioperative Chemotherapy Versus Postoperative Chemotherapy for Locally Advanced Colon Cancer (OPTICAL)
NCT02912559	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair
NCT03125980	PHASE3	RECRUITING	Perioperative Versus Postoperative CapOX Chemotherapy for Locally Advanced Colon Cancer
NCT03426904	PHASE3	ACTIVE_NOT_RECRUITING	Neoadjuvant FOLFOX Chemotherapy for Patients With Locally Advanced Colon Cancer
NCT03428477	PHASE3	ACTIVE_NOT_RECRUITING	EPA for Metastasis Trial 2
NCT03464305	PHASE3	ACTIVE_NOT_RECRUITING	ASPIRIN Trial Belgium
NCT03803553	PHASE3	RECRUITING	Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer
NCT04068103	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Circulating Tumor DNA Testing in Predicting Treatment for Patients With Stage IIA Colon Cancer After Surgery
NCT04089631	PHASE3	RECRUITING	Circulating Tumour DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II Evaluation
NCT05174169	PHASE2/PHASE3	RECRUITING	Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease
NCT05179889	PHASE2/PHASE3	RECRUITING	Adjuvant mFOLFIRINOX for High-risk Stage III Colon Cancer
NCT05194878	PHASE3	RECRUITING	Neoadjuvant FOLFOXIRI Versus Immediate Surgery for Stage II and III Colon Cancers
NCT05534087	PHASE3	RECRUITING	Platform Study of Circulating Tumor DNA Directed Adjuvant Chemotherapy in Colon Cancer (KCSG CO22-12)
NCT05709249	PHASE3	RECRUITING	Xian-Lian-Jie-Du Optimization Decoction As an Adjuvant Treatment for Prevention of Recurrence of Colon Cancer
NCT05710406	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer
NCT06107920	PHASE3	RECRUITING	Neoadjuvant Chemotherapy for Obstructive Colon cancER First Treated by cOlostomy
NCT06293625	PHASE3	RECRUITING	Personalising and Refining Neo-adjuvant Chemotherapy in Locally Advanced but Resecable Colon Cancer in the Elderly of 70 Years Old or More
NCT06446557	PHASE3	NOT_YET_RECRUITING	De-scalation or swItch of Treatment According to Circulating tuMOr DNA Variation After 2 Cycles of Doublet Chemotherapy Plus Targeted Agent in Metastatic Unresectable Colorectal Cancer
NCT06490536	PHASE3	RECRUITING	The Sagittarius Trial
NCT06609551	PHASE3	RECRUITING	ctDNA-guided Selection of Adjuvant Chemotherapy Regimens for Elderly Colon Cancer Patients After Surgery: A Single-center, Randomized, Controlled Study
NCT06686576	PHASE3	RECRUITING	A Study of Neoadjuvant QL1706 in Participants With Untreated dMMR/MSI-H Resectable Colon Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LEUCOVORIN	4	24
PANITUMUMAB	4	9
TIPIRACIL	4	9
OXALIPLATIN	4	8
TRIFLURIDINE	4	7
ASPIRIN	4	6
BEVACIZUMAB	4	5
ENCORAFENIB	4	5
FLUOROURACIL	4	5
IRINOTECAN HYDROCHLORIDE	4	5
FLOXURIDINE	4	4
FRUQUINTINIB	4	4
BINIMETINIB	4	3
CEMIPLIMAB	4	3
CETUXIMAB	4	3
MORPHINE	4	3
PERTUZUMAB	4	3
BUPIVACAINE	4	2
DOSTARLIMAB	4	2
ERLOTINIB HYDROCHLORIDE	4	2
PALBOCICLIB	4	2
PEGFILGRASTIM	4	2
POLYETHYLENE GLYCOL 3350	4	2
RALTITREXED	4	2
RELATLIMAB	4	2
SELPERCATINIB	4	2
TEGAFUR	4	2
TRAMETINIB	4	2
TUCATINIB	4	2
ABEMACICLIB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 24 predictive associations from 24 curated evidence items; also 3 prognostic, 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
KRAS G13D	Cetuximab	Sensitivity/Response	CIViC B	EID6974
JAK1 W690*	Pembrolizumab	Resistance	CIViC C	EID2981
KRAS G12A	Cetuximab	Resistance	CIViC C	EID3717
KRAS G12C	Cetuximab	Resistance	CIViC C	EID3981
KRAS G12D	Cetuximab	Resistance	CIViC C	EID3960
KRAS G12R	Cetuximab	Resistance	CIViC C	EID3998
KRAS G12V	Cetuximab	Resistance	CIViC C	EID3931
KRAS G13D	Cetuximab	Resistance	CIViC C	EID3896
APC Mutation	JW55	Sensitivity/Response	CIViC D	EID445
BRAF V600E	Regorafenib Anhydrous	Sensitivity/Response	CIViC D	EID3776
ERBB2 L755S	Lapatinib + Neratinib + Trastuzumab	Sensitivity/Response	CIViC D	EID1176
ERBB2 L866M	Trastuzumab + Neratinib + Lapatinib	Sensitivity/Response	CIViC D	EID1178
ERBB2 S310F/Y	Neratinib + Trastuzumab + Lapatinib	Sensitivity/Response	CIViC D	EID1179
ERBB2 V777L	Lapatinib + Trastuzumab + Neratinib	Sensitivity/Response	CIViC D	EID1177
ERBB2 V842I	Trastuzumab + Lapatinib + Neratinib	Sensitivity/Response	CIViC D	EID1174
FGFR2 Overexpression	Rogaratinib	Sensitivity/Response	CIViC D	EID7830
KRAS G12V	Regorafenib Anhydrous	Sensitivity/Response	CIViC D	EID3932
KRAS G13D	Regorafenib Anhydrous	Sensitivity/Response	CIViC D	EID3897
MSH3 K383fs	Oxaliplatin + 7-Ethyl-10-Hydroxycamptothecin	Sensitivity/Response	CIViC D	EID9089
BIRC7 Amplification	Cisplatin	Resistance	CIViC D	EID661
CIC Loss	Trametinib	Resistance	CIViC D	EID5111
CIC Loss	Vemurafenib	Resistance	CIViC D	EID5112
POU5F1 EXPRESSION	Oxaliplatin	Resistance	CIViC D	EID958
ZEB1 Expression	Oxaliplatin	Resistance	CIViC D	EID8086