Cancer

Summary

Cancer (MONDO:0004992) is a cancer (an umbrella term covering 33 Mondo subtypes) with 75 cohort genes (389 GWAS associations across 69 studies; 64 CIViC-evidence somatic drivers; 5 ClinVar predisposition records) and 5,123 clinical trials. The dominant Reactome pathway is Constitutive Signaling by Aberrant PI3K in Cancer (14 cohort genes). Molecularly, DPYD DPYD*13 HOMOZYGOSITY confers sensitivity to Capecitabine + Fluorouracil + Tegafur in Cancer (CIViC Level A); 347 further subtype–drug associations are mapped below. Top therapeutic interventions include trametinib, dabrafenib, and darbepoetin alfa.

At a glance

• Classification: Cancer
• Umbrella term: 33 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 389
• ClinVar variants: 5
• Clinical trials: 5,123
• Precision-medicine evidence (CIViC): 348 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cancer
Mondo ID	MONDO:0004992
DOID	DOID:0050686, DOID:0050687, DOID:162
NCIT	C9305
SNOMED CT	363346000
UMLS	C0006826
MedGen	14297
Is cancer (heuristic)	yes

Also known as: CA · cancer · cell type cancer · malignancy · malignant growth · malignant neoplasm · malignant neoplasm (disease) · malignant neoplastic disease · malignant tumor · malignant tumour · MT · neoplasm (disease), malignant · neoplasm, malignant

Data availability: 5 ClinVar variants · 389 GWAS associations (69 studies) · 12 intOGen driver records.

Disease family

An umbrella term covering 33 Mondo subtypes.

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

Related subtypes (47): pre-malignant neoplasm, endocrine gland neoplasm, giant cell tumor, hematopoietic and lymphoid system neoplasm, skin neoplasm, mesenchymal cell neoplasm, epidural spinal canal neoplasm, skeletal muscle neoplasm, trophoblastic neoplasm, germ cell tumor, benign neoplasm, upper aerodigestive tract neoplasm, histiocytoma, embryonal neoplasm, head and neck neoplasm, epithelial neoplasm, reproductive system neoplasm, non-seminomatous lesion, odontogenic cyst, phosphaturic mesenchymal tumor, thyroglossal duct cyst, hamartoma, mesenchymoma, mesothelial neoplasm, peritoneal neoplasm, virus associated tumor, nail tumor, respiratory tract neoplasm, spindle cell neoplasm, mixed neoplasm, urinary system neoplasm, cystic neoplasm, childhood neoplasm, melanocytic neoplasm, digestive system neoplasm, nervous system neoplasm, neoplasm of thorax, connective tissue neoplasm, bronchial adenomas/carcinoids childhood, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, erythroplakia, retroperitoneal neoplasm, cardiovascular neoplasm, dermoid or epidermoid cyst of the central nervous system, connective and soft tissue neoplasm, NTRK fusion positive cancer, RET fusion positive cancer

Subtypes (33): respiratory system cancer, immune system cancer, musculoskeletal system cancer, integumentary system cancer, peritoneum cancer, cardiovascular cancer, reproductive system cancer, malignant giant cell tumor, digestive system cancer, lipomatous cancer, thoracic cancer, malignant glomus tumor, malignant mesenchymoma, carcinoma, sarcoma, blastoma, head and neck cancer, malignant mixed neoplasm, nervous system cancer, retroperitoneal cancer, malignant germ cell tumor, malignant mesothelioma, malignant urinary system neoplasm, childhood malignant neoplasm, anaplastic cancer, malignant spindle cell neoplasm, high grade malignant neoplasm, malignant endocrine neoplasm, malignant soft tissue neoplasm, secondary malignant neoplasm, refractory malignant neoplasm, malignant adenoma, cancer of unknown primary site

Genetics & variants

GWAS landscape

389 GWAS associations across 69 studies. Top hits map to 37 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs247617	1e-149	HERPUD1 - CETP	?
rs964184	2e-108	ZPR1	?
rs780094	4e-91	GCKR	?
rs6983267	8e-74	PCAT1, CASC8, POU5F1B, CCAT2	G	1.24
rs8082812	5e-67	THEMIS3P - AKR1B1P6	?
rs629301	1e-49	CELSR2	?
rs12203592	1e-49	IRF4	T	1.3
rs11263763	4e-47	HNF1B	A	1.22
rs765547	2e-44	LPL - RPL30P9	?
rs261332	2e-35	ALDH1A2, LIPC-AS1, LIPC	?
rs111362352	5e-33	KLK2	C	1.4
rs73728618	6e-33	HLA-DRB1 - HLA-DQA1	T	1.48
rs12275055	9e-33	SMIM38 - MYEOV	G	1.25
rs9270747	2e-32	HLA-DRB1 - HLA-DQA1	A
rs1728918	1e-31	PPM1G - NRBP1	?
rs7709971	2e-31	C5orf67 - MAP3K1	A	1.18
rs554219	4e-30	LINC01488 - PNCRNA-D	G	1.22
rs62516012	7e-28	POU5F1B, CASC8, PCAT1	C
rs10931936	4e-26	CASP8	?	1.08
rs174547	7e-25	FADS1, FADS2	?
Affx-35293625	2e-23		?	1.11
rs7538876	4e-23	PADI6	?	1.07
rs4420638	1e-22	APOC1	?
rs77375493	4e-22	JAK2	G	1.94
rs7632505	8e-22	SEMA5B	?
rs12931267	1e-21	FANCA	?	1.11
rs4499232	2e-21	SPG7	T	1.19
rs562338	5e-21	APOB - TDRD15	?
rs10941679	5e-21	MRPS30-DT	G	1.13
rs9911515	1e-20	CASC17	A	1.14

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90274732	Lindstrom S	2023	122,977	532,864	Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions.
GCST90079140	Backman JD	2021	66,204	10,165	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083126	Backman JD	2021	66,204	10,165	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90011822	Rashkin SR	2020	64,962	410,350	Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
GCST90011823	Rashkin SR	2020	64,962	410,350	Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
GCST90043946	Jiang L	2021	60,858	395,490	A generalized linear mixed model association tool for biobank-scale data.
GCST90027051	Brandes N	2021	56,634	218,196	Genetic association studies of alterations in protein function expose recessive effects on cancer predisposition.
GCST90078950	Backman JD	2021	36,403	393,153	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90082936	Backman JD	2021	36,403	393,153	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90043628	Jiang L	2021	35,762	418,974	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	2
Tier 2: splice/UTR	4
Tier 3: regulatory	2
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	2

Functional consequences

Consequence	Count
intron_variant	29
intergenic_variant	10
3_prime_UTR_variant	4
non_coding_transcript_exon_variant	2
missense_variant	2
regulatory_region_variant	1
unknown	1
TF_binding_site_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs247617	16	56956804	C>A	0.05	intergenic_variant	HERPUD1 - CETP	1e-149	Tier 4: intronic/intergenic
rs964184	11	116778201	G>C	0.05	3_prime_UTR_variant	ZPR1	2e-108	Tier 2: splice/UTR
rs780094	2	27518370	T>A,C,G	0.05	intron_variant	GCKR	4e-91	Tier 4: intronic/intergenic
rs6983267	8	127401060	G>T	0.05	non_coding_transcript_exon_variant	PCAT1, CASC8, POU5F1B, CCAT2	8e-74	Tier 4: intronic/intergenic
rs8082812	18	8522684	C>A	0.05	intergenic_variant	THEMIS3P - AKR1B1P6	5e-67	Tier 4: intronic/intergenic
rs629301	1	109275684	G>A,C,T	0.05	3_prime_UTR_variant	CELSR2	1e-49	Tier 2: splice/UTR
rs12203592	6	396321	C>G,T	0.177	intron_variant	IRF4	1e-49	Tier 4: intronic/intergenic
rs11263763	17	37743574	A>C,G	0.05	intron_variant	HNF1B	4e-47	Tier 4: intronic/intergenic
rs765547	8	20008763	G>A,C,T	0.05	intergenic_variant	LPL - RPL30P9	2e-44	Tier 4: intronic/intergenic
rs261332	15	58435126	A>G	0.05	non_coding_transcript_exon_variant	ALDH1A2, LIPC-AS1, LIPC	2e-35	Tier 4: intronic/intergenic
rs111362352	19	50862184	C>T	0.05	intergenic_variant	KLK2	5e-33	Tier 4: intronic/intergenic
rs73728618	6	32623790	T>A,C	0.05	regulatory_region_variant	HLA-DRB1 - HLA-DQA1	6e-33	Tier 3: regulatory
rs12275055	11	69213892	A>G	0.05	intron_variant	SMIM38 - MYEOV	9e-33	Tier 4: intronic/intergenic
rs9270747	6	32600515	A>G,T	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-32	Tier 4: intronic/intergenic
rs1728918	2	27412596	A>C,G,T	0.05	intron_variant	PPM1G - NRBP1	1e-31	Tier 4: intronic/intergenic
rs7709971	5	56711512	G>A,T	0.05	intron_variant	C5orf67 - MAP3K1	2e-31	Tier 4: intronic/intergenic
rs554219	11	69516874	C>A,G,T	0.05	intergenic_variant	LINC01488 - PNCRNA-D	4e-30	Tier 4: intronic/intergenic
rs62516012	8	127323281	C>A,G	0.05	intron_variant	POU5F1B, CASC8, PCAT1	7e-28	Tier 4: intronic/intergenic
rs10931936	2	201279205	T>A,C,G	0.05	intron_variant	CASP8	4e-26	Tier 4: intronic/intergenic
rs174547	11	61803311	T>C	0.05	intron_variant	FADS1, FADS2	7e-25	Tier 4: intronic/intergenic
Affx-35293625							2e-23	Tier 4: intronic/intergenic
rs7538876	1	17395867	G>A	0.05	intron_variant	PADI6	4e-23	Tier 4: intronic/intergenic
rs4420638	19	44919689	A>G	0.05	intergenic_variant	APOC1	1e-22	Tier 4: intronic/intergenic
rs77375493	9	5073770	G>A,C,T	0	missense_variant	JAK2	4e-22	Tier 1: coding
rs7632505	3	123019460	A>G	0.05	intron_variant	SEMA5B	8e-22	Tier 4: intronic/intergenic
rs12931267	16	89752324	C>G	0.05	intron_variant	FANCA	1e-21	Tier 4: intronic/intergenic
rs4499232	16	89510099	T>A,C,G	0.05	intron_variant	SPG7	2e-21	Tier 4: intronic/intergenic
rs562338	2	21065449	A>C,G,T	0.05	intron_variant	APOB - TDRD15	5e-21	Tier 4: intronic/intergenic
rs10941679	5	44706396	A>G	0.05	intron_variant	MRPS30-DT	5e-21	Tier 4: intronic/intergenic
rs9911515	17	71119217	A>C,G,T	0.05	intron_variant	CASC17	1e-20	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 2 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685425	NM_002907.4(RECQL):c.502-2A>G	RECQL	Likely pathogenic	criteria provided, single submitter
13961	NM_004333.6(BRAF):c.1799T>A (p.Val600Glu)	BRAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
13336	NM_002834.5(PTPN11):c.226G>A (p.Glu76Lys)	PTPN11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
977284	NM_004444.5(EPHB4):c.971C>A (p.Pro324His)	EPHB4	Uncertain significance	no assertion criteria provided
977283	NM_018557.3(LRP1B):c.9120+2T>C	LRP1B	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 317 · 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
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
SLCO1B1			CIViC #8450
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
SMARCA4	Act	BL,BLADDER,BLCA,CCRCC,CHOL,COAD,COADREAD,EGC,ESCA,ESCC,HCC,HNSC,LGGNOS,LUAD,MBL,MLYM,NHL,NSCLC,OVT,PAAD,PANCREAS,PAST,PRCC,SACA,STAD,THYM	CIViC #78
SMO	Act	BCC,GB,HCC,MBL,PAST,PLMESO,SKIN	CIViC #5365
TYMS			CIViC #5971
UGT1A1			CIViC #12422
KMT2C	LoF	ACC,ACYC,AML,ANSC,BCC,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,ES,ESCA,GBC,HCC,HNSC,LUAD,LUSC,MBL,MEL,NPC,OVT,PAAD,PANCREAS,PANET,PAST,PGNG,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,STAD,STOMACH,UCEC,WDTC	CIViC #14089
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CCND2	LoF	AML,CLLSLL	CIViC #9
CCND3	Act	BL,DLBCLNOS,MLYM,NHL	CIViC #10
CBLC			CIViC #9705
CHEK2	Act	BRCA	CIViC #8950
FBXW7	LoF	ANSC,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HNSC,LUAD,LUSC,MBL,NETNOS,NPC,PAAD,PAST,READ,STAD,UCEC,UCS	CIViC #12903
CD44			CIViC #855
CD274	LoF	DLBCLNOS	CIViC #11335
ROBO4			CIViC #12367
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
TUBB3			CIViC #8262
CDK12	LoF	BLCA,CCRCC,CESC,DLBCLNOS,MEL,OVT,PRAD,PROSTATE,STAD	CIViC #12112
DDR2	LoF	HCC	CIViC #51
DNMT3A	LoF	AML,BRCA,CCRCC,HCC,LGGNOS,MDS,PCM,PRCC,WDTC	CIViC #18
DPYD			CIViC #1526
NAPRT			CIViC #17016
DUSP6			CIViC #1567
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
ERBB2	Act	BLCA,BRCA,CESC,CHOL,COADREAD,EGC,ESCA,ESCC,LMS,LUAD,NSCLC,OVT,PRCC,READ,STAD,UCEC	CIViC #20
ERBB3	Act	BLCA,BRCA,CESC,CHOL,COADREAD,NBL,PRAD,STAD,UCEC,UCS,UTUC	CIViC #1733

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
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
SLCO1B1	Orphanet:3111	Rotor syndrome
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

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	11
civic_only	60
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar,civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gwas,civic_evidence
SLCO1B1	HGNC:10959	ENSG00000134538	Q9Y6L6	Solute carrier organic anion transporter family member 1B1	civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	civic_evidence
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	civic_evidence
SMO	HGNC:11119	ENSG00000128602	Q99835	Protein smoothened	civic_evidence
TYMS	HGNC:12441	ENSG00000176890	P04818	Thymidylate synthase	civic_evidence
UGT1A1	HGNC:12530	ENSG00000241635	P22309	UDP-glucuronosyltransferase 1A1	civic_evidence
KMT2C	HGNC:13726	ENSG00000055609	Q8NEZ4	Histone-lysine N-methyltransferase 2C	civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
CCND2	HGNC:1583	ENSG00000118971	P30279	G1/S-specific cyclin-D2	civic_evidence
CCND3	HGNC:1585	ENSG00000112576	P30281	G1/S-specific cyclin-D3	civic_evidence
CBLC	HGNC:15961	ENSG00000142273	Q9ULV8	E3 ubiquitin-protein ligase CBL-C	civic_evidence
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	civic_evidence
FBXW7	HGNC:16712	ENSG00000109670	Q969H0	F-box/WD repeat-containing protein 7	civic_evidence
CD44	HGNC:1681	ENSG00000026508	P16070	CD44 antigen	civic_evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
ROBO4	HGNC:17985	ENSG00000154133	Q8WZ75	Roundabout homolog 4	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
TUBB3	HGNC:20772	ENSG00000258947	Q13509	Tubulin beta-3 chain	civic_evidence
CDK12	HGNC:24224	ENSG00000167258	Q9NYV4	Cyclin-dependent kinase 12	civic_evidence
DDR2	HGNC:2731	ENSG00000162733	Q16832	Discoidin domain-containing receptor 2	civic_evidence
DNMT3A	HGNC:2978	ENSG00000119772	Q9Y6K1	DNA (cytosine-5)-methyltransferase 3A	civic_evidence
DPYD	HGNC:3012	ENSG00000188641	Q12882	Dihydropyrimidine dehydrogenase [NADP(+)]	civic_evidence
NAPRT	HGNC:30450	ENSG00000147813	Q6XQN6	Nicotinate phosphoribosyltransferase	civic_evidence
DUSP6	HGNC:3072	ENSG00000139318	Q16828	Dual specificity protein phosphatase 6	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
ERBB3	HGNC:3431	ENSG00000065361	P21860	Receptor tyrosine-protein kinase erbB-3	civic_evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence
ECSCR	HGNC:35454	ENSG00000249751	Q19T08	Endothelial cell-specific chemotaxis regulator	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence
FLT3	HGNC:3765	ENSG00000122025	P36888	Receptor-type tyrosine-protein kinase FLT3	civic_evidence
FLT3LG	HGNC:3766	ENSG00000090554	P49771	Fms-related tyrosine kinase 3 ligand	civic_evidence
AKT1	HGNC:391	ENSG00000142208	P31749	RAC-alpha serine/threonine-protein kinase	civic_evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	civic_evidence
GNA11	HGNC:4379	ENSG00000088256	P29992	Guanine nucleotide-binding protein subunit alpha-11	civic_evidence
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	civic_evidence
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	civic_evidence
KMT2A	HGNC:7132	ENSG00000118058	Q03164	Histone-lysine N-methyltransferase 2A	civic_evidence
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	civic_evidence
ABL1	HGNC:76	ENSG00000097007	P00519	Tyrosine-protein kinase ABL1	civic_evidence
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	civic_evidence
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	civic_evidence

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.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
SLCO1B1	Solute carrier organic anion transporter family member 1B1	Mediates the Na(+)-independent uptake of organic anions.
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.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SMO	Protein smoothened	G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling.
TYMS	Thymidylate synthase	Catalyzes the reductive methylation of 2’-deoxyuridine 5’-monophosphate (dUMP) to thymidine 5’-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to…
UGT1A1	UDP-glucuronosyltransferase 1A1	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
KMT2C	Histone-lysine N-methyltransferase 2C	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
CCND2	G1/S-specific cyclin-D2	Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
CCND3	G1/S-specific cyclin-D3	Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
CBLC	E3 ubiquitin-protein ligase CBL-C	Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome.
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.
FBXW7	F-box/WD repeat-containing protein 7	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CD44	CD44 antigen	Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment.
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
ROBO4	Roundabout homolog 4	Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
TUBB3	Tubulin beta-3 chain	Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers.
CDK12	Cyclin-dependent kinase 12	Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation.
DDR2	Discoidin domain-containing receptor 2	Tyrosine kinase involved in the regulation of tissues remodeling.
DNMT3A	DNA (cytosine-5)-methyltransferase 3A	Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development.
DPYD	Dihydropyrimidine dehydrogenase [NADP(+)]	Involved in pyrimidine base degradation.
NAPRT	Nicotinate phosphoribosyltransferase	Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate.
DUSP6	Dual specificity protein phosphatase 6	Dual specificity protein phosphatase, which mediates dephosphorylation and inactivation of MAP kinases.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
ERBB2	Receptor tyrosine-protein kinase erbB-2	Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
ERBB3	Receptor tyrosine-protein kinase erbB-3	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
ECSCR	Endothelial cell-specific chemotaxis regulator	Regulates endothelial chemotaxis and tube formation.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
FLT3	Receptor-type tyrosine-protein kinase FLT3	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells.
FLT3LG	Fms-related tyrosine kinase 3 ligand	Stimulates the proliferation of early hematopoietic cells by activating FLT3.
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.
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
GNA11	Guanine nucleotide-binding protein subunit alpha-11	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
IDH1	Isocitrate dehydrogenase [NADP] cytoplasmic	Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
KMT2A	Histone-lysine N-methyltransferase 2A	Histone methyltransferase that plays an essential role in early development and hematopoiesis.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).
ABL1	Tyrosine-protein kinase ABL1	Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autopha…
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
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.

Protein-family classification

Druggable: 44 · Difficult: 8 · Unknown: 23 · Druggable fraction: 0.59

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	24	8.9×	8e-16
Ion channel	3	4.5×	0.164
Complement	1	3.6×	0.525
Phosphatase	2	2.2×	0.525
Antibody/Immunoglobulin	4	1.6×	0.525
Enzyme (other)	8	1.3×	0.525
Transporter	1	1.0×	0.977
Transcription factor	7	0.8×	1.000
Other/Unknown	23	0.6×	1.000
GPCR	1	0.3×	1.000
Scaffold/PPI	1	0.2×	1.000

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
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
SLCO1B1	Transporter	yes		Kazal_dom, OATP, MFS_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
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
SMO	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
TYMS	Enzyme (other)	yes	2.1.1.45	Thymidylate_synthase, Thymidylate_synthase_AS, Thymidate_synth/dCMP_Mease_dom
UGT1A1	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
KMT2C	Transcription factor	no		HMGI/Y_DNA-bd_CS, SET_dom, Znf_RING
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CCND2	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CCND3	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CBLC	Transcription factor	no		Znf_RING, Adaptor_Cbl_N_hlx, EF-hand-dom_pair
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
FBXW7	Scaffold/PPI	no		WD40_rpt, F-box_dom, WD40/YVTN_repeat-like_dom_sf
CD44	Other/Unknown	no		Link_dom, CD44_antigen, C-type_lectin-like/link_sf
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
ROBO4	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
TUBB3	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
CDK12	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
DDR2	Kinase	yes	2.7.10.1	FA58C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
DNMT3A	Complement	yes	2.1.1.37	PWWP_dom, C5_MeTfrase, C5_DNA_meth_AS
DPYD	Enzyme (other)	yes	1.3.1.2	Dihydroorotate_DH_cat, Helical_ferredxn, Aldolase_TIM
NAPRT	Enzyme (other)	yes	6.3.4.21	Nic_PRibTrfase_pncB, Nic_PRibTrfase-Fam, Aldolase_TIM
DUSP6	Phosphatase	yes	3.1.3.16	Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Rhodanese-like_dom
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB2	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ERBB3	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
ECSCR	Other/Unknown	no		ECSCR
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
FLT3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
FLT3LG	Other/Unknown	no		Flt3_lig, 4_helix_cytokine-like_core
AKT1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
GNA11	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
IDH1	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
KMT2A	Transcription factor	no		SET_dom, Bromodomain, Znf_PHD
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
ABL1	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
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

Expression context

Cohort genes with no expression data: 0.

72 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)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	10
calcaneal tendon	9
ganglionic eminence	7
male germ line stem cell (sensu Vertebrata) in testis	7
colonic epithelium	6
secondary oocyte	5
cortical plate	5
sural nerve	5
oocyte	4
stromal cell of endometrium	4
adrenal tissue	4
lower esophagus mucosa	4
tibia	4
dorsal root ganglion	4
endothelial cell	4
buccal mucosa cell	3
right lobe of liver	3
primordial germ cell in gonad	3
embryo	3
upper arm skin	3

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
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
SLCO1B1	29	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
SMO	225	ubiquitous	marker	ventricular zone, left ovary, right ovary
TYMS	262	ubiquitous	marker	ventricular zone, embryo, trabecular bone tissue
UGT1A1	79	tissue_specific	marker	duodenum, right lobe of liver, liver
KMT2C	261	ubiquitous	marker	oocyte, caput epididymis, upper arm skin
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CCND2	293	ubiquitous	marker	adrenal tissue, seminal vesicle, cauda epididymis
CCND3	287	ubiquitous	marker	granulocyte, thymus, blood
CBLC	135	broad	marker	mucosa of transverse colon, lower esophagus mucosa, skin of abdomen
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
FBXW7	290	ubiquitous	marker	Brodmann (1909) area 23, calcaneal tendon, colonic epithelium
CD44	294	ubiquitous	marker	parotid gland, stromal cell of endometrium, mammalian vulva
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
ROBO4	254	broad	marker	lower lobe of lung, apex of heart, omental fat pad
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
TUBB3	144	ubiquitous	marker	cortical plate, ganglionic eminence, embryo
CDK12	259	ubiquitous	marker	buccal mucosa cell, sural nerve, secondary oocyte
DDR2	270	ubiquitous	marker	cauda epididymis, tendon of biceps brachii, vena cava
DNMT3A	223	ubiquitous	marker	sural nerve, ganglionic eminence, ventricular zone
DPYD	274	ubiquitous	marker	germinal epithelium of ovary, monocyte, mononuclear cell
NAPRT	134	ubiquitous	marker	mucosa of transverse colon, right lobe of liver, lower esophagus mucosa
DUSP6	296	ubiquitous	marker	parotid gland, pericardium, monocyte
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
ERBB3	274	broad	marker	trigeminal ganglion, jejunal mucosa, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 151.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
AKT1	16,601
KRAS	14,509
PTEN	11,626
ERBB2	9,659
EZH2	9,646
NTRK1	9,181
BRCA1	9,064
CCND1	8,328

Intra-cohort edges

A	B	Sources
ABL1	ATM	biogrid_interaction, intact
ABL1	EGFR	intact
ABL1	RB1	biogrid_interaction
ABL1	TP53	string_interaction
AKT1	ATM	intact
AKT1	CBLC	biogrid_interaction
AKT1	CCND1	string_interaction
AKT1	CCND3	string_interaction
AKT1	GNA11	intact
AKT1	HRAS	string_interaction
AKT1	PIK3CA	biogrid_interaction, string_interaction
AKT1	PTEN	string_interaction
ALK	CD274	string_interaction
ALK	KRAS	string_interaction
ALK	NRAS	string_interaction
ALK	RET	intact
ATM	BRCA1	string_interaction
ATM	BRCA2	string_interaction
ATM	CDK12	string_interaction
ATM	CHEK2	string_interaction
ATM	GNA11	biogrid_interaction
ATM	MLH1	string_interaction
ATM	MSH2	string_interaction
ATM	PRKAA2	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
ATRX	BRCA2	string_interaction
ATRX	EZH2	intact
ATRX	IDH1	string_interaction
ATRX	TP53	string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	EGFR	biogrid_interaction
BRAF	FBXW7	biogrid_interaction
BRAF	GNA11	intact, string_interaction
BRAF	HRAS	intact, string_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MLH1	string_interaction
BRAF	NF1	string_interaction
BRAF	NRAS	biogrid_interaction, intact, string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
BRCA1	BRCA2	string_interaction
BRCA1	CDK12	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	MLH1	string_interaction
BRCA1	MSH2	string_interaction
BRCA1	NF1	string_interaction
BRCA1	TP53	string_interaction
BRCA2	CCND1	intact
BRCA2	CDK12	string_interaction

Structural data

PDB: 67 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
TP53	P04637	313
HRAS	P01112	246
PIK3CA	P42336	135
BRAF	P15056	131
ABL1	P00519	85
FGFR1	P11362	83
ALK	Q9UM73	79
CD274	Q9NZQ7	76
NTRK1	P04629	65
ERBB2	P04626	63
TYMS	P04818	61
IDH1	O75874	61
KMT2A	Q03164	60
KIT	P10721	52
DNMT3A	Q9Y6K1	43
AKT1	P31749	43
CDK12	Q9NYV4	39
CHEK2	O96017	38
EZH2	Q15910	38
NRAS	P01111	35
RET	P07949	34
BRCA1	P38398	33
SMARCA4	P51532	31
MSH2	P43246	30
TUBB3	Q13509	28
NF1	P21359	26
TRPV6	Q9H1D0	24
ERBB3	P21860	23

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DPYD	Q12882	96.23
UGT1A1	P22309	91.19
CNIH3	Q8TBE1	85.15
ROBO4	Q8WZ75	57.67
ECSCR	Q19T08	57.07
ZNF652	Q9Y2D9	56.60
SLTM	Q9NWH9	52.38
LRP1B	Q9NZR2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 742. Enrichment computed across 79 evidence-associated genes (69 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 69 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Constitutive Signaling by Aberrant PI3K in Cancer	14	25.8×	9e-14	EGFR, ERBB2, ERBB3, FGFR1, FGFR3, FLT3, FLT3LG, KIT (+6 more)
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	15	21.0×	9e-14	EGFR, ERBB2, ERBB3, FGFR1, FGFR3, FLT3, FLT3LG, AKT1 (+7 more)
RAF/MAP kinase cascade	17	15.1×	1e-13	BRAF, EGFR, ERBB2, ERBB3, FGFR1, FGFR3, FLT3, FLT3LG (+9 more)
PIP3 activates AKT signaling	15	14.5×	1e-11	EGFR, ERBB2, ERBB3, FGFR1, FGFR3, FLT3, FLT3LG, AKT1 (+7 more)
Signaling by ERBB2 KD Mutants	8	49.0×	4e-10	EGFR, ERBB2, ERBB3, HRAS, KRAS, NRAS, NRG1, PIK3CA
FLT3 Signaling	8	40.1×	2e-09	FLT3, FLT3LG, AKT1, HRAS, KRAS, NRAS, PIK3CA, PTPN11
SHC1 events in ERBB2 signaling	7	48.3×	6e-09	EGFR, ERBB2, ERBB3, HRAS, KRAS, NRAS, NRG1
Signaling by ERBB2 TMD/JMD mutants	7	48.3×	6e-09	EGFR, ERBB2, ERBB3, HRAS, KRAS, NRAS, NRG1
Signaling by FLT3 ITD and TKD mutants	6	66.2×	2e-08	FLT3, HRAS, KRAS, NRAS, PIK3CA, PTPN11
Signaling by ERBB2 ECD mutants	6	58.4×	3e-08	EGFR, ERBB2, HRAS, KRAS, NRAS, PIK3CA
GRB2 events in ERBB2 signaling	6	55.2×	5e-08	EGFR, ERBB2, HRAS, KRAS, NRAS, NRG1
Activated NTRK2 signals through FRS2 and FRS3	5	69.0×	3e-07	HRAS, KRAS, NRAS, NTRK2, PTPN11
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	5	63.7×	5e-07	HRAS, KRAS, NRAS, PDGFRA, PIK3CA
Signaling by PDGFRA extracellular domain mutants	5	63.7×	5e-07	HRAS, KRAS, NRAS, PDGFRA, PIK3CA
Downstream signal transduction	6	33.1×	1e-06	HRAS, KRAS, NRAS, PDGFRA, PIK3CA, PTPN11
Constitutive Signaling by EGFRvIII	5	51.7×	1e-06	EGFR, HRAS, KRAS, NRAS, PIK3CA
RAS signaling downstream of NF1 loss-of-function variants	4	94.6×	2e-06	HRAS, KRAS, NF1, NRAS
PI3K events in ERBB2 signaling	5	48.7×	2e-06	EGFR, ERBB2, ERBB3, NRG1, PIK3CA
Tie2 Signaling	5	43.5×	3e-06	HRAS, KRAS, NRAS, PIK3CA, PTPN11
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	41.4×	4e-06	EGFR, HRAS, KRAS, NRAS, PIK3CA
Diseases of DNA repair	5	41.4×	4e-06	BRCA1, BRCA2, MLH1, MSH2, ATM
FRS-mediated FGFR3 signaling	5	39.4×	4e-06	FGFR3, HRAS, KRAS, NRAS, PTPN11
Activated NTRK3 signals through RAS	4	73.6×	5e-06	HRAS, KRAS, NRAS, NTRK3
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	37.6×	5e-06	HRAS, KIT, KRAS, NRAS, PIK3CA
PI3K Cascade	6	23.6×	5e-06	FGFR1, FGFR3, FLT3, FLT3LG, PIK3CA, PTPN11
Signaling by RAS GAP mutants	3	165.5×	6e-06	HRAS, KRAS, NRAS
Signaling by RAS GTPase mutants	3	165.5×	6e-06	HRAS, KRAS, NRAS
Signaling by FGFR3 in disease	5	36.0×	6e-06	FGFR3, HRAS, KRAS, NRAS, PIK3CA
EGFR Transactivation by Gastrin	4	66.2×	6e-06	EGFR, HRAS, KRAS, NRAS
Activated NTRK2 signals through RAS	4	66.2×	6e-06	HRAS, KRAS, NRAS, NTRK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 79 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	15	14.9×	9e-11	DDR2, EGFR, ERBB3, FGFR1, FGFR3, FLT3, KIT, NTRK1 (+7 more)
cell surface receptor protein tyrosine kinase signaling pathway	11	24.2×	6e-10	DDR2, ERBB2, ERBB3, FLT3, ALK, NRG1, NTRK1, NTRK2 (+3 more)
protein autophosphorylation	11	20.2×	3e-09	CHEK2, DDR2, FGFR1, FLT3, AKT1, ALK, KIT, ATM (+3 more)
positive regulation of ERK1 and ERK2 cascade	13	14.0×	3e-09	BRAF, FBXW7, CD44, DDR2, EGFR, FGFR3, HRAS, ABL1 (+5 more)
neuron apoptotic process	9	21.1×	1e-07	TP53, ERBB3, HRAS, KRAS, ABL1, NF1, ATM, NTRK1 (+1 more)
epidermal growth factor receptor signaling pathway	8	25.1×	2e-07	BRAF, EGFR, ERBB2, ERBB3, AKT1, ABL1, PIK3CA, PTPN11
MAPK cascade	9	17.4×	4e-07	BRAF, DUSP6, FGFR1, FGFR3, HRAS, KRAS, NF1, NRAS (+1 more)
negative regulation of neuron apoptotic process	10	14.0×	4e-07	BRAF, CCND1, CBLC, ERBB3, HRAS, KRAS, MSH2, NTRK1 (+2 more)
positive regulation of MAPK cascade	11	11.2×	5e-07	EGFR, ERBB2, ERBB3, FGFR1, FGFR3, FLT3, HRAS, KIT (+3 more)
positive regulation of cell population proliferation	15	6.4×	1e-06	SMARCA4, CCND2, EGFR, EZH2, FGFR1, FGFR3, FLT3, FLT3LG (+7 more)
peptidyl-tyrosine phosphorylation	6	32.0×	4e-06	DDR2, ERBB2, FGFR1, FLT3, NTRK1, PDGFRA
positive regulation of G1/S transition of mitotic cell cycle	6	30.5×	5e-06	CCND1, CCND2, CCND3, DDR2, EGFR, AKT1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	18.7×	1e-05	EGFR, ERBB2, ERBB3, AKT1, NF1, PIK3CA, PTEN
positive regulation of gene expression	13	6.4×	1e-05	BRAF, TP53, BRCA1, SMO, ERBB3, AKT1, KRAS, ATM (+5 more)
signal transduction	19	3.9×	2e-05	CCND3, CBLC, CD274, DDR2, DUSP6, EGFR, ERBB2, ERBB3 (+11 more)
response to UV-A	3	160.0×	3e-05	CCND1, EGFR, AKT1
positive regulation of cell migration	10	7.8×	5e-05	SMO, EGFR, EZH2, AKT1, HRAS, KIT, ATM, NTRK3 (+2 more)
Schwann cell development	4	53.3×	6e-05	ERBB2, ERBB3, HRAS, NF1
cellular response to xenobiotic stimulus	6	18.3×	7e-05	BRAF, TP53, CHEK2, KCNE2, PRKAA2, RB1
mechanoreceptor differentiation	3	128.0×	7e-05	NTRK1, NTRK2, NTRK3
wound healing	6	17.3×	8e-05	ERBB2, ERBB3, NF1, NRG1, PDGFRA, PPL
response to X-ray	4	44.9×	1e-04	TP53, BRCA2, CCND1, MSH2
B cell differentiation	6	16.6×	1e-04	EZH2, FLT3, FLT3LG, KIT, MSH2, NTRK1
Ras protein signal transduction	6	15.6×	1e-04	TP53, HRAS, KRAS, NF1, NRAS, RB1
double-strand break repair	6	15.4×	1e-04	TP53, BRCA1, BRCA2, CHEK2, MSH2, ATM
negative regulation of apoptotic process	12	5.3×	1e-04	BRAF, TP53, SMO, CCND2, CD44, DDR2, EGFR, ERBB2 (+4 more)
DNA damage response, signal transduction by p53 class mediator	5	22.7×	1e-04	TP53, BRCA2, CHEK2, ATM, ATRX
myeloid progenitor cell differentiation	3	91.4×	2e-04	BRAF, FLT3, KIT
intrinsic apoptotic signaling pathway in response to DNA damage	5	20.5×	2e-04	BRCA1, CHEK2, MLH1, ABL1, ATM
visual learning	5	19.4×	3e-04	BRAF, KIT, KRAS, KMT2A, NF1

Therapeutics

Drug target analysis

Approved (phase 4): 42 · Phase ≥3: 44 · Phased (≥1): 48 · Undrugged: 27

Druggability breadth: 61 of 79 evidence-associated genes (77%) 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
TP53	NITROFURANTOIN
SLCO1B1	CANDESARTAN CILEXETIL
BRCA1	RIBOFLAVIN
SMO	INFIGRATINIB
TYMS	FOLIC ACID
UGT1A1	ATAZANAVIR
CCND1	PALBOCICLIB
CCND2	PALBOCICLIB
CCND3	PALBOCICLIB
CHEK2	NERATINIB
CD274	MOCLOBEMIDE
SLTM	CABOZANTINIB
TUBB3	COLCHICINE
DDR2	PONATINIB
NAPRT	PHENYLBUTAZONE
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
ERBB3	MOBOCERTINIB
EZH2	TAZEMETOSTAT
FGFR1	PONATINIB
FGFR3	PONATINIB
FLT3	PONATINIB
AKT1	CAPIVASERTIB
ALK	CERITINIB
HRAS	LONAFARNIB
IDH1	ENASIDENIB
KIT	PONATINIB
KRAS	VEMURAFENIB
KMT2A	FLUORESCEIN
ABL1	PONATINIB
ATM	AMIODARONE HYDROCHLORIDE
NTRK1	PONATINIB
NTRK2	FEDRATINIB
NTRK3	FEDRATINIB
PDGFRA	PONATINIB
PIK3CA	IDELALISIB
PRKAA2	ADENOSINE PHOSPHATE
RET	PONATINIB
TRPV6	ECONAZOLE
EPHB4	PONATINIB
EPHB6	AFATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KMT2A	535	4
TP53	196	4
EGFR	175	4
FLT3	143	4
RET	135	4
ABL1	122	4
KIT	99	4
FGFR1	93	4
ERBB2	83	4
PDGFRA	77	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF, EGFR, KRAS, RET
PONATINIB	4	ABL1, BRAF, DDR2, EGFR, EPHB4, ERBB2
FEDRATINIB	4	ABL1, ALK, BRAF, DDR2, EGFR, EPHB4
SORAFENIB	4	ABL1, BRAF, DDR2, EGFR, EPHB4, EPHB6
DASATINIB ANHYDROUS	4	ABL1, BRAF, DDR2, EGFR, EPHB4, EPHB6
RUXOLITINIB	4	ABL1, ALK, BRAF, EPHB6, KIT, NTRK1
INFIGRATINIB PHOSPHATE	4	ABL1, ALK, BRAF, FGFR1, FGFR3, FLT3
INFIGRATINIB	4	ABL1, ALK, BRAF, FGFR1, FGFR3, FLT3
REGORAFENIB	4	ABL1, BRAF, DDR2, FGFR1, FLT3, KIT
DABRAFENIB	4	ABL1, BRAF, EPHB6, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	ABL1, BRAF, DDR2, EPHB4, EPHB6, FLT3
ABEMACICLIB	4	BRAF, CCND1, CCND3, EGFR, FLT3, NTRK1
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	ABL1, BRAF, DDR2, EPHB4, EPHB6
PAZOPANIB	4	ABL1, ALK, BRAF, DDR2, EPHB6, FGFR1
DASATINIB	4	ABL1, BRAF, DDR2, EGFR, EPHB4, EPHB6
ERLOTINIB	4	ABL1, ALK, BRAF, EGFR, EPHB4, EPHB6
GEFITINIB	4	ABL1, BRAF, CHEK2, EGFR, EPHB4, EPHB6
IMATINIB	4	ABL1, BRAF, DDR2, EGFR, ERBB2, FLT3
NITROFURANTOIN	4	TP53
DIOSMIN	4	KMT2A, TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	KMT2A, SLCO1B1, TP53
DIENESTROL	4	KMT2A, TP53
CLOTRIMAZOLE	4	EGFR, ERBB2, KMT2A, TP53
COLCHICINE	4	TP53, TUBB3
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	KMT2A, TP53
AMIODARONE HYDROCHLORIDE	4	ATM, KMT2A, TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 35.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
ABL1	3,282	Binding:3254, ADMET:16, Functional:10, Toxicity:2
FLT3	3,132	Binding:3096, Functional:24, ADMET:8, Toxicity:4
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
AKT1	1,942	Binding:1900, Functional:34, ADMET:7, Toxicity:1
ALK	1,815	Binding:1801, Functional:13, ADMET:1
TUBB3	1,781	Binding:1741, Functional:34, ADMET:6
RET	1,586	Binding:1573, Functional:10, ADMET:3
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
NTRK1	1,194	Binding:1182, ADMET:7, Functional:5
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
FGFR3	975	Binding:948, Functional:18, ADMET:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
EZH2	839	Binding:833, Functional:6
CHEK2	690	Binding:687, Functional:2, ADMET:1
CCND1	576	Binding:574, Functional:1, ADMET:1
NTRK2	554	Binding:547, ADMET:5, Functional:2
PRKAA2	549	Binding:548, Functional:1
CD274	525	Binding:520, Functional:5
IDH1	488	Binding:475, Functional:12, ADMET:1
EPHB4	437	Binding:437
CCND3	425	Binding:422, ADMET:2, Toxicity:1
NTRK3	408	Binding:400, Functional:4, ADMET:4
DDR2	389	Binding:386, ADMET:3
TYMS	376	Binding:373, ADMET:2, Functional:1
CDK12	347	Binding:341, Functional:6
SLCO1B1	242	Functional:106, ADMET:82, Binding:53, Toxicity:1
ATM	240	Binding:233, Functional:5, ADMET:2
SMARCA4	230	Binding:207, ADMET:12, Functional:11
KMT2A	188	Binding:180, Functional:8
UGT1A1	174	ADMET:159, Binding:15
ERBB3	169	Binding:169
SMO	131	Binding:111, Functional:20
DNMT3A	120	Binding:118, ADMET:1, Functional:1
EPHB6	87	Binding:87
RB1	59	Binding:59
HRAS	48	Binding:45, Functional:3
DUSP6	38	Binding:37, ADMET:1
TRPV6	32	Binding:32
KMT2C	29	Binding:29
CCND2	28	Binding:28
GNA11	18	Binding:18
NRAS	18	Binding:18
NAPRT	16	Binding:16
SLTM	14	Binding:14
BRCA1	13	Binding:9, Functional:4

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
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
TYMS	2.1.1.45	thymidylate synthase
UGT1A1	2.4.1.17	glucuronosyltransferase
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
CDK12	2.7.11.22, 2.7.11.23	cyclin-dependent kinase, [RNA-polymerase]-subunit kinase
DDR2	2.7.10.1	receptor protein-tyrosine kinase
DNMT3A	2.1.1.37	DNA (cytosine-5-)-methyltransferase
DPYD	1.3.1.2	dihydropyrimidine dehydrogenase (NADP+)
NAPRT	6.3.4.21	nicotinate phosphoribosyltransferase
DUSP6	3.1.3.16, 3.1.3.48	protein-serine/threonine phosphatase, protein-tyrosine-phosphatase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
ERBB3	2.7.10.1	receptor protein-tyrosine kinase
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
FLT3	2.7.10.1	receptor protein-tyrosine kinase
AKT1	2.7.11.1	non-specific serine/threonine protein kinase
ALK	2.7.10.1	receptor protein-tyrosine kinase
HRAS	3.6.5.2	small monomeric GTPase
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)
KIT	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
ABL1	2.7.10.2	non-specific protein-tyrosine kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
NTRK1	2.7.10.1	receptor protein-tyrosine kinase
NTRK2	2.7.10.1	receptor protein-tyrosine kinase
NTRK3	2.7.10.1	receptor protein-tyrosine 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
PRKAA2	2.7.11.1, 2.7.11.31	non-specific serine/threonine protein kinase, [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
RET	2.7.10.1	receptor protein-tyrosine kinase
EPHB4	2.7.10.1	receptor protein-tyrosine kinase

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
TP53	869
SLCO1B1	242
SMARCA4	230
SMO	131
TYMS	376
UGT1A1	174
CCND1	576
CCND3	425
CHEK2	690
CD274	525
TUBB3	1,781
CDK12	347
DDR2	389
DNMT3A	120
EGFR	6,531
ERBB2	1,221
ERBB3	169
EZH2	839
FGFR1	1,465
FGFR3	975
FLT3	3,132
AKT1	1,942
ALK	1,815
IDH1	488
KIT	2,305
KRAS	861
KMT2A	188
ABL1	3,282
ATM	240

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 3.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
SLCO1B1	1
UGT1A1	1
DPYD	1

Drug repurposing candidates

26 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, EGFR, KRAS, RET
PONATINIB	4	ABL1, BRAF, DDR2, EGFR, EPHB4, ERBB2
FEDRATINIB	4	ABL1, ALK, BRAF, DDR2, EGFR, EPHB4
SORAFENIB	4	ABL1, BRAF, DDR2, EGFR, EPHB4, EPHB6
DASATINIB ANHYDROUS	4	ABL1, BRAF, DDR2, EGFR, EPHB4, EPHB6
RUXOLITINIB	4	ABL1, ALK, BRAF, EPHB6, KIT, NTRK1
INFIGRATINIB PHOSPHATE	4	ABL1, ALK, BRAF, FGFR1, FGFR3, FLT3
INFIGRATINIB	4	ABL1, ALK, BRAF, FGFR1, FGFR3, FLT3
REGORAFENIB	4	ABL1, BRAF, DDR2, FGFR1, FLT3, KIT
NILOTINIB	4	ABL1, BRAF, DDR2, EPHB4, EPHB6, FLT3
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	ABL1, BRAF, DDR2, EPHB4, EPHB6
DASATINIB	4	ABL1, BRAF, DDR2, EGFR, EPHB4, EPHB6
ERLOTINIB	4	ABL1, ALK, BRAF, EGFR, EPHB4, EPHB6
GEFITINIB	4	ABL1, BRAF, CHEK2, EGFR, EPHB4, EPHB6
IMATINIB	4	ABL1, BRAF, DDR2, EGFR, ERBB2, FLT3
NITROFURANTOIN	4	TP53
DIOSMIN	4	KMT2A, TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	KMT2A, SLCO1B1, TP53
DIENESTROL	4	KMT2A, TP53
CLOTRIMAZOLE	4	EGFR, ERBB2, KMT2A, TP53
COLCHICINE	4	TP53, TUBB3
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	KMT2A, TP53
AMIODARONE HYDROCHLORIDE	4	ATM, KMT2A, TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	42	BRAF, TP53, SLCO1B1, BRCA1, SMO, TYMS, UGT1A1, CCND1, CCND2, CCND3 (+32 more)
B	Phased (≥1) drug, not yet approved	6	SMARCA4, CDK12, DPYD, NRAS, RB1, TRPV5
C	Druggable family + PDB, no drug	6	DNMT3A, DUSP6, NRG1, PTEN, KCNE2, PIP
D	Druggable family + AlphaFold only, no drug	1	ROBO4
E	Difficult family or no structure, no drug	20	BRCA2, KMT2C, CBLC, FBXW7, CD44, ECSCR, FLT3LG, GNA11, MLH1, MSH2 (+10 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNMT3A	120	EZH2
BRCA2	0	BRCA1
FLT3LG	0	FLT3
GNA11	18	BRAF, NRAS
NF1	0	KRAS, BRAF, NRAS
NRG1	0	EGFR, ERBB3
PTCH1	4	SMO
PTEN	8	TP53, AKT1
KMT2C	29	—
CBLC	5	—
FBXW7	0	—
CD44	9	—
ROBO4	0	—
DUSP6	38	—
ECSCR	0	—
MLH1	0	—
MSH2	9	—
ATRX	0	—
TMX1	3	—
GLYR1	0	—
CNIH3	0	—
ZNF652	0	—
RCAN1	0	—
KCNE2	0	—
LRP1B	0	—
PHB1	7	—
PIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5,123.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	447
PHASE1/PHASE2	231
PHASE3	222
PHASE4	77
PHASE1	77
PHASE2/PHASE3	46

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04475705	PHASE4	RECRUITING	Propofol vs Sevo for Paediatric Tumor Surgery
NCT05078671	PHASE4	RECRUITING	Pharmacokinetic Boosting of Olaparib to Improve Exposure, Tolerance and Cost-effectiveness
NCT06118710	PHASE4	RECRUITING	Evaluation of the Omission of Dexamethasone in Premedication Regimens During Paclitaxel Treatment
NCT06183437	PHASE4	RECRUITING	The STOP-MED CTRCD Trial
NCT06603870	PHASE4	RECRUITING	Secondary Prevention of VTE in Patients With Cancer and Catheter-Related Upper Extremity Deep Vein Thrombosis
NCT07303816	PHASE4	NOT_YET_RECRUITING	Statins to Prevent Cancer Associated Blood Clots
NCT00075179	PHASE4	TERMINATED	Natrecor in Pulmonary Hypertension
NCT00106886	PHASE4	UNKNOWN	HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study)
NCT00153868	PHASE4	COMPLETED	A Web-based Study of Quality of Life Benefits Associated Aranesp in Anemic Patients With Cancer
NCT00171964	PHASE4	COMPLETED	Efficacy and Tolerability of Zoledronic Acid With Radiotherapy in Pts With Advanced Osteolytic Bone Lesions
NCT00198276	PHASE4	COMPLETED	Study Using the MedPulser Electroporation System With Bleomycin to Treat Cutaneous and Subcutaneous Cancer
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00274885	PHASE4	UNKNOWN	Relationship Between Platinum Levels in the Blood and Neurotoxicity in Patients Who Are Receiving Oxaliplatin for Gastrointestinal Cancer
NCT00358111	PHASE4	TERMINATED	Study of LUMA Cervical Imaging System as Adjunct to Colposcopy
NCT00381095	PHASE4	TERMINATED	A Study To Evaluate Pregabalin In The Treatment Of Moderate To Severe Chronic Bone Pain Related To Metastatic Cancer
NCT00450645	PHASE4	UNKNOWN	Residual Vein Thrombosis and the Optimal Duration of Low Molecular Weight Heparin in Cancer Patients With Deep Vein Thrombosis
NCT00491946	PHASE4	UNKNOWN	A Pharmacokinetic Study of Actinomycin-D and Vincristine in Children With Cancer
NCT00495378	PHASE4	TERMINATED	RAPID-2. A Study to Evaluate the Effectiveness of Alternate Dosing of PROCRIT (Epoetin Alfa) in Maintaining Hemoglobin Levels in Patients With Chemotherapy Related Anemia
NCT00524407	PHASE4	COMPLETED	Effect of Epoetin Alfa on Hemoglobin, Symptom Distress, and Quality of Life in Patients Receiving Chemotherapy
NCT00533143	PHASE4	COMPLETED	Non-invasive Ventilation in Terminally Ill Cancer Patients
NCT00606515	PHASE4	COMPLETED	Pharmacokinetics Study of Liposomal Paclitaxel in Humans
NCT00646945	PHASE4	COMPLETED	Study of the Efficacy of Kalinox® 170 Bar in Adult Oncology
NCT00688038	PHASE4	COMPLETED	Correlation of MR Thermal Imaging to Actual Size of Ablation During Laser Ablation Therapy
NCT00747916	PHASE4	TERMINATED	Safety, Efficacy, and Side Effects Study of Interventional Cryotherapy in the Pleural Space(ICE PLS)
NCT00819832	PHASE4	TERMINATED	Anderson Circulating Tumor Cell Burden (CTCB) Study
NCT00902720	PHASE4	UNKNOWN	Ovarian Tissue Freezing For Fertility Preservation
NCT00942968	PHASE4	COMPLETED	Evaluation of Dalteparin for Long-term (One Year) Treatment of Blood Clots in Subjects With Cancer
NCT00951262	PHASE4	COMPLETED	Intervention Study on Life Review Among Advanced Cancer Patients in Fuzhou, China
NCT01006356	PHASE4	COMPLETED	An Efficacy and Safety Study of Hydromorphone Hydrochloride (HCl) Oral Osmotic System (OROS) in the Reduction of Breakthrough Pain Medication Frequency in Participants With Cancer
NCT01017172	PHASE4	UNKNOWN	Safety and Immune Response to Adjuvanted A(H1N1)v Influenza Vaccine in HIV-1 Infected and Immunosuppressed Adult Patients
NCT01022905	PHASE4	COMPLETED	Vaccine Responses to Influenza A H1N1/09 Immunization in High-risk Patients
NCT01040884	PHASE4	COMPLETED	Safety And Accuracy Study Of The Actisight™ Needle Guidance System In Patients Undergoing CT-Guided Procedures
NCT01143974	PHASE4	COMPLETED	Trial of Pemetrexed in Combined With Cisplatin for the Treatment of Advanced Breast Cancer
NCT01189409	PHASE4	TERMINATED	Polyethylene Glycol (PEG) Versus Sennosides Study in Opioid-Induced Constipation in Cancer Patients
NCT01205230	PHASE4	COMPLETED	VEG113971: An Open-Label Study of the Effects of Ketoconazole or Esomeprazole on Pazopanib PK
NCT01302509	PHASE4	COMPLETED	Enteral Nutrition in Cancer Patient
NCT01304446	PHASE4	COMPLETED	Enteral Nutrition in Cancer Patients
NCT01313247	PHASE4	UNKNOWN	Paracetamol for Cancer Pain
NCT01313780	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Safety of Oxycodone/Naloxone Compared to OxyContin in Korean Cancer Patients
NCT01318473	PHASE4	COMPLETED	The Use of the ActiSight™ Needle Guidance System in Patients Undergoing CT-Guided With Lesions Smaller Than 15 mm

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRAMETINIB	4	14
DABRAFENIB	4	11
DARBEPOETIN ALFA	4	10
PALONOSETRON	4	7
PANITUMUMAB	4	6
ABEMACICLIB	4	5
ALECTINIB	4	5
AXITINIB	4	5
EPOETIN ALFA	4	5
OXYCODONE	4	5
COBIMETINIB	4	4
DALTEPARIN SODIUM	4	4
ENTRECTINIB	4	4
HALOPERIDOL	4	4
METHADONE	4	4
NALOXONE	4	4
NIRAPARIB	4	4
OLAPARIB	4	4
VENETOCLAX	4	4
APIXABAN	4	3
CABOZANTINIB	4	3
CHOLECALCIFEROL	4	3
DENOSUMAB	4	3
EDOXABAN	4	3
MEGESTROL ACETATE	4	3
MELATONIN	4	3
MIRTAZAPINE	4	3
MODAFINIL	4	3
PAZOPANIB	4	3
RUCAPARIB	4	3

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 348 predictive associations from 356 curated evidence items; also 100 oncogenic, 5 prognostic, 3 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
DPYD DPYD*13 HOMOZYGOSITY	Capecitabine + Fluorouracil + Tegafur	Adverse Response	CIViC A	EID1801
DPYD DPYD*2A HOMOZYGOSITY	Tegafur + Capecitabine + Fluorouracil	Adverse Response	CIViC A	EID1800
DPYD RS67376798 HOMOZYGOSITY	Tegafur + Fluorouracil + Capecitabine	Adverse Response	CIViC A	EID1803
UGT1A1 UGT1A1*28	Belinostat	Adverse Response	CIViC A	EID1792
AKT1 E17K	Capivasertib	Sensitivity/Response	CIViC B	EID3039 +1
PIK3CA Mutation	Capivasertib	Sensitivity/Response	CIViC B	EID3040 +1
ALK Fusion	Entrectinib	Sensitivity/Response	CIViC B	EID2952
ALK Fusion OR v::ROS1 Fusion	Crizotinib	Sensitivity/Response	CIViC B	EID11671
BRAF K601E	Vemurafenib	Sensitivity/Response	CIViC B	EID5963
BRAF V600E	Trametinib + Dabrafenib	Sensitivity/Response	CIViC B	EID11672
BRAF V600E OR NRAS Mutation OR HRAS Mutation OR KRAS Mutation OR NF1 Inactivating Mutation	Selumetinib	Sensitivity/Response	CIViC B	EID11696
BRAF V600E OR NRAS Mutation OR HRAS Mutation OR KRAS Mutation OR NF1 Mutation	Selumetinib	Sensitivity/Response	CIViC B	EID11681
BRCA1 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID1370
BRCA2 Mutation	Olaparib	Sensitivity/Response	CIViC B	EID1371
CCND1 Amplification	Ribociclib	Sensitivity/Response	CIViC B	EID7789
CCND1 Amplification OR CCND2 Amplification OR CCND3 Amplification	Palbociclib	Sensitivity/Response	CIViC B	EID11673
CD274 Expression	Nivolumab	Sensitivity/Response	CIViC B	EID1517
ECSCR EXPRESSION	Angiogenesis Inhibitor	Sensitivity/Response	CIViC B	EID1165
ERBB2 Activating Mutation	Afatinib	Sensitivity/Response	CIViC B	EID11676
ERBB2 Activating Mutation OR ERBB2 T790M	Osimertinib	Sensitivity/Response	CIViC B	EID12026
ERBB2 Amplification	Trastuzumab + Pertuzumab	Sensitivity/Response	CIViC B	EID12025
ERBB2 V777L	Neratinib	Sensitivity/Response	CIViC B	EID12106
EZH2 Mutation OR SMARCA4 Loss OR SMARCB1 Loss	Tazemetostat	Sensitivity/Response	CIViC B	EID11694
FBXW7 Mutation	MTOR Inhibitor	Sensitivity/Response	CIViC B	EID1631
FGFR1 Amplification OR FGFR2 Amplification OR FGFR3 Amplification OR FGFR4 Amplification	Erdafitinib	Sensitivity/Response	CIViC B	EID12024
FGFR1 Amplification OR FGFR2 Mutation OR v::FGFR1 Fusion OR FGFR2 Amplification OR FGFR3 Mutation OR FGFR3::v Fusion	Fexagratinib	Sensitivity/Response	CIViC B	EID11675
FGFR2::v Fusion	Erdafitinib	Sensitivity/Response	CIViC B	EID1918
FGFR3::TACC3 Fusion	Erdafitinib	Sensitivity/Response	CIViC B	EID1919
KMT2C Mutation OR KMT2A Mutation	Immunotherapy	Sensitivity/Response	CIViC B	EID12031
KRAS G12C	Sotorasib	Sensitivity/Response	CIViC B	EID8068

+318 more predictive associations (showing top 30 by evidence level).