Lung cancer

Summary

Lung cancer (MONDO:0008903) is a cancer (an umbrella term covering 7 Mondo subtypes) caused by EGFR (GenCC Definitive), with 45 cohort genes (263 GWAS associations across 41 studies; 29 CIViC-evidence somatic drivers; 517 ClinVar predisposition records) and 3,711 clinical trials. The dominant Reactome pathway is RAF/MAP kinase cascade (8 cohort genes). Molecularly, EGFR Mutation confers sensitivity to Gefitinib in Lung Cancer (CIViC Level B); 30 further subtype–drug associations are mapped below. Top therapeutic interventions include paclitaxel, vinorelbine, and docetaxel anhydrous.

At a glance

• Classification: Cancer
• Causal gene: EGFR (GenCC Definitive)
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 45
• GWAS associations: 263
• ClinVar variants: 517
• Clinical trials: 3,711
• Precision-medicine evidence (CIViC): 31 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lung cancer
Mondo ID	MONDO:0008903
OMIM	211980
DOID	DOID:1324
NCIT	C7377
SNOMED CT	363358000
UMLS	C0242379
MedGen	66885
Anatomy (UBERON)	UBERON:0002048
Is cancer (heuristic)	yes

Also known as: adenocarcinoma of lung, response to tyrosine kinase inhibitor in, autosomal dominant, somatic mutation · adenocarcinoma of lung, somatic · cancer of lung · lung cancer · lung cancer, protection against, autosomal dominant, somatic mutation · lung cancer, resistance to, autosomal dominant, somatic mutation · lung cancer, somatic · lung cancer, susceptibility to, autosomal dominant, somatic mutation · malignant lung neoplasm · malignant lung tumor · malignant lung tumour · malignant neoplasm of lung · malignant neoplasm of the lung · malignant tumor of lung · malignant tumor of the lung · malignant tumour of lung · malignant tumour of the lung · nonsmall cell lung cancer, response to tyrosine kinase inhibitor in, autosomal dominant, somatic mutation · nonsmall cell lung cancer, somatic · nonsmall cell lung cancer, susceptibility to, autosomal dominant, somatic mutation

Data availability: 517 ClinVar variants · 263 GWAS associations (41 studies) · 5 GenCC gene-disease records.

Disease family

An umbrella term covering 7 Mondo subtypes.

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

Related subtypes (8): nasal cavity cancer, tracheal cancer, bronchus cancer, larynx cancer, pharynx cancer, pleural cancer, SMARCA4-deficient sarcoma of thorax, paranasal sinus cancer

Subtypes (7): lung sarcoma, lung meningioma, lung lymphoma, lung hilum cancer, lung carcinoma, malignant superior sulcus neoplasm, Graham-Boyle-Troxell syndrome

Genetics & variants

GWAS landscape

263 GWAS associations across 41 studies. Top hits map to 28 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2036527	8e-179	PSMA4 - CHRNA5	A	1.26
rs16886181	5e-122	C5orf67 - MAP3K1	T
rs55781567	5e-115	CHRNA5	G	1.24
rs421284	2e-58	CLPTM1L	T	1.13
rs56113850	1e-43	CYP2A6	T	0.89
rs380286	5e-42	CLPTM1L	A	0.88
rs31490	8e-40	CLPTM1L	A	0.88
rs1794514	8e-33	HLA-DQB1 - MTCO3P1	C	1.15
rs11571815	7e-32	BRCA2	A	1.7
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
rs3131856	2e-27	SUMO2P1 - MOG	T	0.85
rs7726159	6e-26	TERT	?	0.1
rs1219651	1e-25	FGFR2	?	1.09
rs4143333	6e-25	ZDHHC20P2	G	1.16
rs7177201	4e-24	ADAMTS7	T	0.89
rs2736108	5e-24	TERT - MIR4457	C
rs2853677	8e-24	TERT	?	0.84
rs7705526	2e-23	TERT	A	1.11
rs9267123	3e-23	LINC01149 - HCP5	C	1.16
rs7097066	7e-22	ZMIZ1	G
rs2981584	1e-21	FGFR2	?	0.94
rs3217992	2e-21	CDKN2B, CDKN2B-AS1	C
rs10908278	3e-21	HNF1B	?	1.06
rs7643161	4e-21	TPRG1 - TP63	?	0.09
chr15:78618839	1e-20		?	0.19
rs11571833	1e-20	BRCA2	A	0.64
rs9258381	3e-20	HLA-F-AS1	A	1.11
chr15:78590583	8e-20		?	0.2
rs113623975	3e-19	EPHX2 - GULOP	G	0.87
rs7953330	1e-18	WNK1	C	0.92

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90270343	Guo H	2023	122,977	121,835	A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers.
GCST90651054	Sato G	2023	43,098	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90455518	Gorman BR	2024	39,664	119,158	Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.
GCST90455521	Gorman BR	2024	39,664	119,158	Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.
GCST90308764	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651069	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90570627	You D	2025	29,266	163,593	A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases.
GCST90570628	You D	2025	29,266	457,923	A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases.
GCST90570629	You D	2025	29,266	496,111	A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases.
GCST90243964	Gabriel AAG	2022	29,266	251,837	Genetic analysis of lung cancer and the germline impact on somatic mutation burden.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	9
non_coding_transcript_exon_variant	2
unknown	2
5_prime_UTR_variant	1
splice_region_variant	1
3_prime_UTR_variant	1
stop_gained	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2036527	15	78559273	G>A,C,T	0.348	intergenic_variant	PSMA4 - CHRNA5	8e-179	Tier 4: intronic/intergenic
rs16886181	5	56733416	T>A,C,G	0.05	intergenic_variant	C5orf67 - MAP3K1	5e-122	Tier 4: intronic/intergenic
rs55781567	15	78565644	C>G	0.37	5_prime_UTR_variant	CHRNA5	5e-115	Tier 2: splice/UTR
rs421284	5	1325475	T>C,G	0.444	intron_variant	CLPTM1L	2e-58	Tier 4: intronic/intergenic
rs56113850	19	40847202	T>C	0.449	intron_variant	CYP2A6	1e-43	Tier 4: intronic/intergenic
rs380286	5	1320132	G>A	0.44	intron_variant	CLPTM1L	5e-42	Tier 4: intronic/intergenic
rs31490	5	1344343	G>A,T	0.421	splice_region_variant	CLPTM1L	8e-40	Tier 2: splice/UTR
rs1794514	6	32699696	G>A,C,T	0.17	intergenic_variant	HLA-DQB1 - MTCO3P1	8e-33	Tier 4: intronic/intergenic
rs11571815	13	32394413	G>A	0.01	intron_variant	BRCA2	7e-32	Tier 4: intronic/intergenic
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
rs3131856	6	29639324	T>C	0.088	intron_variant	SUMO2P1 - MOG	2e-27	Tier 4: intronic/intergenic
rs7726159	5	1282204	C>A	0.05	intron_variant	TERT	6e-26	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
rs4143333	6	31380742	A>G	0.08	non_coding_transcript_exon_variant	ZDHHC20P2	6e-25	Tier 4: intronic/intergenic
rs7177201	15	78773038	T>C,G	0.25	intron_variant	ADAMTS7	4e-24	Tier 4: intronic/intergenic
rs2736108	5	1297373	C>T	0.05	intergenic_variant	TERT - MIR4457	5e-24	Tier 4: intronic/intergenic
rs2853677	5	1287079	G>A,C,T	0.05	intron_variant	TERT	8e-24	Tier 4: intronic/intergenic
rs7705526	5	1285859	C>A,G,T	0.342	intron_variant	TERT	2e-23	Tier 4: intronic/intergenic
rs9267123	6	31459618	G>C	0.126	intron_variant	LINC01149 - HCP5	3e-23	Tier 4: intronic/intergenic
rs7097066	10	79129101	G>A,C,T	0.05	intron_variant	ZMIZ1	7e-22	Tier 4: intronic/intergenic
rs2981584	10	121590702	A>C,G,T	0.05	intron_variant	FGFR2	1e-21	Tier 4: intronic/intergenic
rs3217992	9	22003224	C>A,G,T	0.05	3_prime_UTR_variant	CDKN2B, CDKN2B-AS1	2e-21	Tier 2: splice/UTR
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	3e-21	Tier 4: intronic/intergenic
rs7643161	3	189624850	T>C,G	0.05	intron_variant	TPRG1 - TP63	4e-21	Tier 4: intronic/intergenic
chr15:78618839							1e-20	Tier 4: intronic/intergenic
rs11571833	13	32398489	A>T	0.01	stop_gained	BRCA2	1e-20	Tier 1: coding
rs9258381	6	29785571	G>A	0.14	intron_variant	HLA-F-AS1	3e-20	Tier 4: intronic/intergenic
chr15:78590583							8e-20	Tier 4: intronic/intergenic
rs113623975	8	27555088	A>G	0.116	intergenic_variant	EPHX2 - GULOP	3e-19	Tier 4: intronic/intergenic
rs7953330	12	889653	G>C	0.29	intron_variant	WNK1	1e-18	Tier 4: intronic/intergenic

ClinVar germline variants

517 retrieved; paginated sample, class counts are floors:

156 uncertain significance, 115 benign/likely benign, 84 conflicting classifications of pathogenicity, 51 likely benign, 33 pathogenic/likely pathogenic, 29 likely pathogenic, 25 benign, 18 pathogenic, 3 confers sensitivity, 2 drug response, 1 benign; confers sensitivity

ClinVar	Variant (HGVS)	Gene	Classification	Review
13973	NM_004333.6(BRAF):c.770A>G (p.Gln257Arg)	BRAF	Pathogenic	reviewed by expert panel
13976	NM_004333.6(BRAF):c.1495A>G (p.Lys499Glu)	BRAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162795	NM_004333.6(BRAF):c.2135C>A (p.Ala712Asp)	BRAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
41446	NM_004333.6(BRAF):c.1801A>C (p.Lys601Gln)	BRAF	Pathogenic	criteria provided, multiple submitters, no conflicts
55601	NM_007294.4(BRCA1):c.5503C>T (p.Arg1835Ter)	BRCA1	Pathogenic	reviewed by expert panel
2578363	NM_005228.5(EGFR):c.2317delinsAACCCCT (p.His773delinsAsnProTyr)	EGFR	Pathogenic	criteria provided, single submitter
1034077	NM_000124.4(ERCC6):c.2093dup (p.Thr699fs)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
1068941	NM_000124.4(ERCC6):c.2792_2802del (p.Ile931fs)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073323	NM_000124.4(ERCC6):c.2170-1G>A	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1701	NM_000124.4(ERCC6):c.2203C>T (p.Arg735Ter)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
1703	NM_000124.4(ERCC6):c.1357C>T (p.Arg453Ter)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
1705	NM_000124.4(ERCC6):c.1971_1974dup (p.Thr659fs)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
1711	NM_000124.4(ERCC6):c.2047C>T (p.Arg683Ter)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190147	NM_000124.4(ERCC6):c.1526+1G>T	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190150	NM_000124.4(ERCC6):c.1518del (p.Lys506fs)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190160	NM_000124.4(ERCC6):c.2167C>T (p.Gln723Ter)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190162	NM_000124.4(ERCC6):c.2599-26A>G	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190167	NM_000124.4(ERCC6):c.3536del (p.Tyr1179fs)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
190170	NM_000124.4(ERCC6):c.3904C>T (p.Gln1302Ter)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
190171	NM_000124.4(ERCC6):c.3952_3953del (p.Arg1318fs)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2000913	NM_000124.4(ERCC6):c.1717_1720del (p.Cys573fs)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
212733	NM_000124.4(ERCC6):c.466C>T (p.Gln156Ter)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225905	NM_000124.4(ERCC6):c.643G>T (p.Glu215Ter)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
430298	NM_000124.4(ERCC6):c.1834C>T (p.Arg612Ter)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
432341	NM_000124.4(ERCC6):c.355G>T (p.Glu119Ter)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
502165	NM_000124.4(ERCC6):c.2839C>T (p.Arg947Ter)	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522698	NM_000124.4(ERCC6):c.2551T>A (p.Trp851Arg)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
550657	NM_000124.4(ERCC6):c.2286+1G>A	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
550722	NM_000124.4(ERCC6):c.1009A>T (p.Lys337Ter)	ERCC6	Pathogenic	criteria provided, multiple submitters, no conflicts
551374	NM_000124.4(ERCC6):c.2287-2A>G	ERCC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 163 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
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
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
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
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
CMTR2	LoF	LUAD
NQO1			CIViC #1463
ETV4	Act	NBL	CIViC #1767
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29
ARAF	Act	CHOL,LUAD,SCLC	CIViC #3
MAP2K7	LoF	STAD	CIViC #4546
PDCD4			CIViC #10573
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
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
CASP8	LoF	BCC,BLCA,BRCA,CEAD,CESC,CSCC,HNSC,NHL,NPC,STAD,VULVA	CIViC #761
CHEK2	Act	BRCA	CIViC #8950
PALB2	LoF	OVT	CIViC #15013
ERCC6			CIViC #1742
ALK	Act	BRCA,HCC,NBL,NSCLC,PROSTATE,SCLC	CIViC #1
SMAD3	LoF	COADREAD,PAAD	CIViC #3376
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
KMT2D	LoF	ACYC,ALL,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,CSCC,DLBCLNOS,ESCA,GBM,HCC,HGGNOS,HNSC,LNM,LUSC,MBL,MLYM,NBL,NETNOS,NHL,NPC,NSCLC,OVT,PAAD,PANCREAS,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SCLC,SKCM,STAD,STOMACH,UCEC,UCS	CIViC #64
NFE2L2	Act	BLCA,CESC,ESCA,HCC,HNSC,LUSC,NSCLC,PRCC,UCEC	CIViC #3878
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69
PRKN			CIViC #4103
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37
BARD1	Act	PRAD	CIViC #549

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
EGFR	Definitive	Autosomal dominant	lung cancer	9
CHRNB4	Limited	Autosomal dominant	lung cancer
CMTR2	Limited	Autosomal dominant	lung cancer	2
ERBB2	Limited	Autosomal dominant	lung cancer	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
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
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
ETV4	Orphanet:319	Skeletal Ewing sarcoma
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis

Cohort genes → proteins

45 cohort genes, 40 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	10
civic_only	9
multi_evidence	26

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	gencc,clinvar,civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	gencc,clinvar
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar,civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	civic_evidence
CHRNB4	HGNC:1964	ENSG00000117971	P30926	Neuronal acetylcholine receptor subunit beta-4	gencc
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
CMTR2	HGNC:25635	ENSG00000180917	Q8IYT2	Cap-specific mRNA (nucleoside-2’-O-)-methyltransferase 2	gencc
NQO1	HGNC:2874	ENSG00000181019	P15559	NAD(P)H dehydrogenase [quinone] 1	civic_evidence
ETV4	HGNC:3493	ENSG00000175832	P43268	ETS translocation variant 4	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
ARAF	HGNC:646	ENSG00000078061	P10398	Serine/threonine-protein kinase A-Raf	civic_evidence
MAP2K7	HGNC:6847	ENSG00000076984	O14733	Dual specificity mitogen-activated protein kinase kinase 7	civic_evidence
PDCD4	HGNC:8763	ENSG00000150593	Q53EL6	Programmed cell death protein 4	civic_evidence
BMP2	HGNC:1069	ENSG00000125845	P12643	Bone morphogenetic protein 2	clinvar
SLC19A1	HGNC:10937	ENSG00000173638	P41440	Reduced folate transporter	clinvar
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
FASLG	HGNC:11936	ENSG00000117560	P48023	Tumor necrosis factor ligand superfamily member 6	clinvar
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
CASP8	HGNC:1509	ENSG00000064012	Q14790	Caspase-8	clinvar
CHEK2	HGNC:16627	ENSG00000183765	O96017	Serine/threonine-protein kinase Chk2	clinvar
HRH4	HGNC:17383	ENSG00000134489	Q9H3N8	Histamine H4 receptor	gwas
ZRANB1	HGNC:18224	ENSG00000019995	Q9UGI0	Ubiquitin thioesterase ZRANB1	gwas
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	clinvar
ERCC6	HGNC:3438	ENSG00000225830	P0DP91	Chimeric ERCC6-PGBD3 protein	clinvar
ATP8B1	HGNC:3706	ENSG00000081923	O43520	Phospholipid-transporting ATPase IC	gwas
EGFR-AS1	HGNC:40207	ENSG00000224057		EGFR antisense RNA 1	clinvar
TNPO1-DT	HGNC:40328	ENSG00000249085		TNPO1 divergent transcript	gwas
MIR4675	HGNC:41619	ENSG00000265372		microRNA 4675	gwas
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	clinvar
GRIK1	HGNC:4579	ENSG00000171189	P39086	Glutamate receptor ionotropic, kainate 1	gwas
LINC01377	HGNC:50642	ENSG00000249808		long intergenic non-protein coding RNA 1377	gwas
LINC02039	HGNC:52879	ENSG00000248107		long intergenic non-protein coding RNA 2039	gwas
SMAD3	HGNC:6769	ENSG00000166949	P84022	SMAD family member 3	clinvar
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	clinvar
SMAD9	HGNC:6774	ENSG00000120693	O15198	SMAD family member 9	clinvar
MAP7	HGNC:6869	ENSG00000135525	Q14244	Ensconsin	gwas
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	clinvar
KMT2D	HGNC:7133	ENSG00000167548	O14686	Histone-lysine N-methyltransferase 2D	clinvar
NFE2L2	HGNC:7782	ENSG00000116044	Q16236	Nuclear factor erythroid 2-related factor 2	clinvar
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar
PRKN	HGNC:8607	ENSG00000185345	O60260	E3 ubiquitin-protein ligase parkin	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar
BARD1	HGNC:952	ENSG00000138376	Q99728	BRCA1-associated RING domain protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CHRNB4	Neuronal acetylcholine receptor subunit beta-4	Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection…
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
CMTR2	Cap-specific mRNA (nucleoside-2’-O-)-methyltransferase 2	S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap2 2’-O-ribose methylation to the 5’-cap structure of mRNAs.
NQO1	NAD(P)H dehydrogenase [quinone] 1	Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors.
ETV4	ETS translocation variant 4	Transcriptional activator.
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.
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…
ARAF	Serine/threonine-protein kinase A-Raf	Involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
MAP2K7	Dual specificity mitogen-activated protein kinase kinase 7	Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway.
PDCD4	Programmed cell death protein 4	Inhibits translation initiation and cap-dependent translation.
BMP2	Bone morphogenetic protein 2	Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis.
SLC19A1	Reduced folate transporter	Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
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.
FASLG	Tumor necrosis factor ligand superfamily member 6	Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
CASP8	Caspase-8	Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood.
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.
HRH4	Histamine H4 receptor	G protein-coupled receptor primarily expressed in immune cells such as mast cells, eosinophils, basophils, dendritic cells and neutrophils that plays a key role in immune and inflammatory responses.
ZRANB1	Ubiquitin thioesterase ZRANB1	Ubiquitin thioesterase, which specifically hydrolyzes ‘Lys-29’-linked and ‘Lys-33’-linked diubiquitin.
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.
ERCC6	Chimeric ERCC6-PGBD3 protein	Involved in repair of DNA damage following UV irradiation, acting either in the absence of ERCC6 or synergistically with ERCC6.
ATP8B1	Phospholipid-transporting ATPase IC	Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of phospholipids, in particular phosphatidylcholines (PC), from the outer to the inner leaflet of the plasma membrane.
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.
GRIK1	Glutamate receptor ionotropic, kainate 1	Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid.
SMAD3	SMAD family member 3	Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases.
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
SMAD9	SMAD family member 9	Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase.
MAP7	Ensconsin	Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells.
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
KMT2D	Histone-lysine N-methyltransferase 2D	Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
NFE2L2	Nuclear factor erythroid 2-related factor 2	Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes the…
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.
PRKN	E3 ubiquitin-protein ligase parkin	Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
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.
BARD1	BRCA1-associated RING domain protein 1	E3 ubiquitin-protein ligase.

Protein-family classification

Druggable: 18 · Difficult: 9 · Unknown: 18 · Druggable fraction: 0.4

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	11	6.8×	3e-06
Complement	1	6.0×	0.457
Transcription factor	8	1.5×	0.457
Transporter	1	1.7×	0.838
Enzyme (other)	4	1.1×	0.838
Other/Unknown	18	0.7×	0.989
GPCR	1	0.5×	0.989
Scaffold/PPI	1	0.4×	0.989

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CHRNB4	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
CMTR2	Enzyme (other)	yes	2.1.1.296	RNA_MeTrfase_FtsJ_dom, Adrift-typ_MeTrfase, SAM-dependent_MTases_sf
NQO1	Enzyme (other)	yes	1.6.5.2	Flavodoxin_fold, Flavoprotein-like_sf, NAD(P)H_dehydrogenase_qn
ETV4	Other/Unknown	no		Ets_dom, ETS_PEA3_N, WH-like_DNA-bd_sf
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
ARAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
MAP2K7	Kinase	yes	2.7.12.2	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
PDCD4	Other/Unknown	no		Initiation_fac_eIF4g_MI, ARM-type_fold, PDCD4
BMP2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
SLC19A1	Transporter	yes		Folate_carrier, SLC19A1, MFS_trans_sf
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
FASLG	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
CASP8	Enzyme (other)	yes	3.4.22.61	Pept_C14_p20, DED_dom, Pept_C14_p10
CHEK2	Kinase	yes	2.7.11.1	FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
HRH4	GPCR	yes		GPCR_Rhodpsn, Histamine_H4_rcpt, GPCR_Rhodpsn_7TM
ZRANB1	Transcription factor	no		Znf_RanBP2, OTU_dom, Znf_RanBP2_sf
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
ERCC6	Other/Unknown	no		PGBD, PiggyBac_TE-derived, CC_ERCC-6_N
ATP8B1	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
EGFR-AS1	Other/Unknown	no
TNPO1-DT	Other/Unknown	no
MIR4675	Other/Unknown	no
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
GRIK1	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
LINC01377	Other/Unknown	no
LINC02039	Other/Unknown	no
SMAD3	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
SMAD9	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
MAP7	Other/Unknown	no		MAP7_fam, MAP7_domain-containing
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
KMT2D	Transcription factor	no		SET_dom, Znf_RING, Znf_PHD
NFE2L2	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
PRKN	Transcription factor	no	2.3.2.27	Ubiquitin-like_dom, IBR_dom, Parkin
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
BARD1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, Ankyrin_rpt

Expression context

Cohort genes with no expression data: 0.

38 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)	45
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	10
calcaneal tendon	7
primordial germ cell in gonad	5
buccal mucosa cell	5
sural nerve	4
ventricular zone	4
oocyte	4
secondary oocyte	4
nipple	3
tendon of biceps brachii	3
gastrocnemius	3
hindlimb stylopod muscle	3
endothelial cell	3
lower esophagus mucosa	2
ganglionic eminence	2
jejunal mucosa	2
stromal cell of endometrium	2
granulocyte	2
cartilage tissue	2
blood	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CHRNB4	125	broad	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, right testis
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
CMTR2	253	ubiquitous	yes	germinal epithelium of ovary, ileal mucosa, jejunal mucosa
NQO1	285	ubiquitous	marker	endometrium epithelium, gall bladder, stromal cell of endometrium
ETV4	171	ubiquitous	marker	primordial germ cell in gonad, type B pancreatic cell, olfactory bulb
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
ARAF	262	ubiquitous	marker	hindlimb stylopod muscle, granulocyte, gastrocnemius
MAP2K7	273	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, gastrocnemius
PDCD4	296	ubiquitous	marker	body of pancreas, skin of abdomen, skin of leg
BMP2	238	broad	marker	cartilage tissue, pancreatic ductal cell, pigmented layer of retina
SLC19A1	238	ubiquitous	marker	jejunal mucosa, blood, endothelial cell
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
FASLG	118	tissue_specific	marker	granulocyte, blood, lymph node
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
CASP8	252	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
CHEK2	183	ubiquitous	marker	primordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
HRH4	50	tissue_specific	marker	monocyte, mononuclear cell, leukocyte
ZRANB1	256		yes	tibialis anterior, endothelial cell, deltoid
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
ERCC6	257	ubiquitous	marker	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
ATP8B1	289	ubiquitous	marker	cardia of stomach, nipple, renal medulla
EGFR-AS1	112	tissue_specific	yes	primordial germ cell in gonad, bone marrow, thymus
TNPO1-DT	116		yes	male germ line stem cell (sensu Vertebrata) in testis, cortical plate, ventricular zone
MIR4675	37		yes	calcaneal tendon, gastrocnemius, kidney

Protein interactions among cohort

Intra-cohort edges: 44.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
KRAS	14,509
PRKN	10,281
ERBB2	9,659
BRCA1	9,064
BRAF	7,394
ATM	7,383
SMAD4	7,320
SMAD3	6,440

Intra-cohort edges

A	B	Sources
ALK	KRAS	string_interaction
ARAF	BRAF	biogrid_interaction, intact
ARAF	KRAS	biogrid_interaction, intact
ATM	BARD1	string_interaction
ATM	BRCA1	string_interaction
ATM	CHEK2	string_interaction
ATM	MLH1	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
BARD1	BRCA1	biogrid_interaction, intact, string_interaction
BARD1	CHEK2	string_interaction
BARD1	PALB2	string_interaction
BMP2	SMAD9	string_interaction
BRAF	EGFR	biogrid_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	MLH1	string_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
BRCA1	CHEK2	string_interaction
BRCA1	MLH1	string_interaction
BRCA1	PALB2	biogrid_interaction, intact, string_interaction
BRCA1	TP53	string_interaction
CASP8	FASLG	intact, string_interaction
CHEK2	PALB2	string_interaction
CHEK2	TP53	intact, string_interaction
CSMD1	SMAD3	intact
EGFR	ERBB2	intact, string_interaction
EGFR	PIK3CA	string_interaction
ERBB2	KRAS	string_interaction
ERBB2	PIK3CA	string_interaction
ETV4	KMT2D	biogrid_interaction
ETV4	NFE2L2	intact
KIT	PIK3CA	biogrid_interaction
KIT	TP53	biogrid_interaction
KMT2D	TP53	string_interaction
KRAS	PIK3CA	string_interaction
KRAS	SLC19A1	intact
KRAS	TP53	string_interaction
NFE2L2	NQO1	string_interaction
NQO1	TP53	biogrid_interaction, string_interaction
PDCD4	SMAD4	string_interaction
PIK3CA	SLTM	intact
SMAD3	SMAD4	biogrid_interaction, intact, string_interaction
SMAD3	SMAD9	string_interaction
SMAD4	SMAD9	biogrid_interaction, intact, string_interaction

Structural data

PDB: 38 · AlphaFold-only: 2 · No structure: 5

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
TP53	P04637	313
PIK3CA	P42336	135
BRAF	P15056	131
FGFR1	P11362	83
ALK	Q9UM73	79
ERBB2	P04626	63
KIT	P10721	52
CHEK2	O96017	38
MAP2K7	O14733	37
CASP8	Q14790	36
BRCA1	P38398	33
NQO1	P15559	28
NFE2L2	Q16236	23
BMP2	P12643	21
PRKN	O60260	21
SLC19A1	P41440	19
HRH4	Q9H3N8	15
ATM	Q13315	14
ATP8B1	O43520	13
ERCC6	P0DP91	12
SMAD3	P84022	12
SMAD4	Q13485	12
PDCD4	Q53EL6	11
GRIK1	P39086	11
KMT2D	O14686	11
BARD1	Q99728	11
MLH1	P40692	7
ARAF	P10398	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CMTR2	Q8IYT2	86.01
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 524. Enrichment computed across 45 evidence-associated genes (36 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 36 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAF/MAP kinase cascade	8	13.6×	5e-05	EGFR, ERBB2, KRAS, BRAF, FGFR1, KIT, ARAF, PIK3CA
Signaling by ERBB2 ECD mutants	4	74.6×	5e-05	EGFR, ERBB2, KRAS, PIK3CA
Diseases of DNA repair	4	63.4×	7e-05	BRCA1, MLH1, ATM, BARD1
RUNX3 regulates CDKN1A transcription	3	135.9×	7e-05	TP53, SMAD3, SMAD4
Impaired BRCA2 binding to PALB2	4	50.8×	7e-05	BRCA1, PALB2, ATM, BARD1
Signaling by ERBB2 KD Mutants	4	47.0×	7e-05	EGFR, ERBB2, KRAS, PIK3CA
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	4	47.0×	7e-05	BRCA1, PALB2, ATM, BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	4	47.0×	7e-05	BRCA1, PALB2, ATM, BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	4	47.0×	7e-05	BRCA1, PALB2, ATM, BARD1
Disease	13	4.7×	7e-05	BRAF, BRCA1, CASP8, ALK, KIT, ARAF, SMAD3, SMAD4 (+5 more)
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	4	43.8×	9e-05	BRCA1, PALB2, ATM, BARD1
Homologous DNA Pairing and Strand Exchange	4	42.3×	9e-05	BRCA1, PALB2, ATM, BARD1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	5	20.3×	2e-04	BRCA1, TP53, CHEK2, ATM, BARD1
Resolution of D-loop Structures through Holliday Junction Intermediates	4	33.4×	2e-04	BRCA1, PALB2, ATM, BARD1
Defective homologous recombination repair (HRR) due to PALB2 loss of function	3	79.3×	2e-04	BRCA1, ATM, BARD1
Defective DNA double strand break response due to BRCA1 loss of function	2	317.2×	3e-04	BRCA1, BARD1
Defective DNA double strand break response due to BARD1 loss of function	2	317.2×	3e-04	BRCA1, BARD1
Diseases of DNA Double-Strand Break Repair	3	68.0×	3e-04	BRCA1, ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	3	68.0×	3e-04	BRCA1, ATM, BARD1
Constitutive Signaling by Aberrant PI3K in Cancer	5	17.6×	3e-04	EGFR, ERBB2, FGFR1, KIT, PIK3CA
G2/M DNA damage checkpoint	5	16.7×	3e-04	BRCA1, TP53, CHEK2, ATM, BARD1
Stabilization of p53	3	63.4×	3e-04	TP53, CHEK2, ATM
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	3	63.4×	3e-04	EGFR, ERBB2, KIT
Regulation of TP53 Activity through Phosphorylation	5	16.4×	3e-04	BRCA1, TP53, CHEK2, ATM, BARD1
Constitutive Signaling by EGFRvIII	3	59.5×	3e-04	EGFR, KRAS, PIK3CA
PI3K events in ERBB2 signaling	3	56.0×	4e-04	EGFR, ERBB2, PIK3CA
RNA Polymerase II Transcription	9	5.6×	4e-04	BMP2, BRCA1, KIT, SMAD3, SMAD4, MLH1, KMT2D, ATM (+1 more)
GRB2 events in ERBB2 signaling	3	52.9×	4e-04	EGFR, ERBB2, KRAS
Resolution of D-Loop Structures	3	52.9×	4e-04	BRCA1, ATM, BARD1
Loss of Function of SMAD4 in Cancer	2	211.5×	5e-04	SMAD3, SMAD4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 40 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 gene expression	11	10.7×	3e-06	KRAS, BMP2, BRAF, BRCA1, TP53, ERCC6, SMAD3, SMAD4 (+3 more)
intrinsic apoptotic signaling pathway in response to DNA damage	5	40.5×	7e-05	BRCA1, CHEK2, ERCC6, MLH1, ATM
positive regulation of miRNA transcription	5	36.3×	8e-05	EGFR, BMP2, TP53, SMAD3, SMAD4
positive regulation of transcription by RNA polymerase II	13	4.8×	3e-04	EGFR, BMP2, BRCA1, TP53, ERCC6, ETV4, SMAD3, SMAD4 (+5 more)
somitogenesis	4	37.5×	7e-04	TP53, PALB2, SMAD3, ATM
negative regulation of protein catabolic process	4	36.6×	7e-04	EGFR, NQO1, SMAD3, SMAD4
protein K6-linked ubiquitination	3	74.3×	7e-04	BRCA1, PRKN, BARD1
replicative senescence	3	74.3×	7e-04	TP53, CHEK2, ATM
extrinsic apoptotic signaling pathway	4	30.6×	7e-04	FASLG, CASP8, SMAD3, SMAD4
MAPK cascade	5	19.1×	7e-04	KRAS, BMP2, BRAF, FGFR1, ARAF
protein autophosphorylation	5	18.2×	7e-04	CHEK2, FGFR1, ALK, KIT, ATM
positive regulation of apoptotic process	7	9.9×	7e-04	BMP2, FASLG, TP53, CASP8, ATM, PRKN, BARD1
negative regulation of reactive oxygen species metabolic process	3	70.2×	7e-04	BRCA1, TP53, PRKN
positive regulation of neuron apoptotic process	4	27.2×	9e-04	FASLG, TP53, CASP8, ATM
negative regulation of apoptotic process	8	7.0×	1e-03	EGFR, ERBB2, BRAF, TP53, PALB2, ARAF, SMAD3, BARD1
positive regulation of peptidyl-serine phosphorylation	3	57.5×	0.001	EGFR, BRAF, ARAF
epidermal growth factor receptor signaling pathway	4	24.8×	0.001	EGFR, ERBB2, BRAF, PIK3CA
SMAD protein signal transduction	3	55.0×	0.001	SMAD3, SMAD4, SMAD9
cellular response to xenobiotic stimulus	4	24.1×	0.001	BRAF, TP53, CHEK2, NFE2L2
regulation of transforming growth factor beta2 production	2	210.7×	0.002	SMAD3, SMAD4
cellular response to gamma radiation	3	45.1×	0.002	TP53, CHEK2, ATM
response to gamma radiation	3	43.6×	0.002	TP53, ERCC6, SMAD3
double-strand break repair	4	20.3×	0.002	BRCA1, TP53, CHEK2, ATM
positive regulation of cell migration	6	9.3×	0.002	EGFR, BMP2, CASP8, KIT, SMAD3, ATM
BMP signaling pathway	4	20.1×	0.002	BMP2, SMAD4, SMAD9, PDCD4
cellular response to BMP stimulus	3	42.1×	0.002	BMP2, SMAD4, SMAD9
positive regulation of DNA-templated transcription	8	5.6×	0.003	BMP2, BRCA1, TP53, CHEK2, SMAD3, SMAD4, MAP2K7, NFE2L2
chordate embryonic development	2	140.4×	0.003	BRCA1, FGFR1
myeloid progenitor cell differentiation	2	120.4×	0.004	BRAF, KIT
transforming growth factor beta receptor signaling pathway	4	15.9×	0.004	TP53, SMAD3, SMAD4, SMAD9

Therapeutics

Drug target analysis

Approved (phase 4): 23 · Phase ≥3: 24 · Phased (≥1): 24 · Undrugged: 21

Druggability breadth: 29 of 45 evidence-associated genes (64%) 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
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
KRAS	VEMURAFENIB
TP53	NITROFURANTOIN
CHRNB4	VARENICLINE
SLTM	CABOZANTINIB
NQO1	DICUMAROL
FGFR1	PONATINIB
KIT	PONATINIB
ARAF	VEMURAFENIB
MAP2K7	NERATINIB
PDCD4	SIROLIMUS
SLC19A1	PRALATREXATE
BRAF	VEMURAFENIB
BRCA1	RIBOFLAVIN
CASP8	PRIMAQUINE PHOSPHATE
CHEK2	NERATINIB
HRH4	DESLORATADINE
ALK	CERITINIB
SMAD3	FLUORESCEIN
NFE2L2	DIMETHYL FUMARATE
ATM	AMIODARONE HYDROCHLORIDE
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
KIT	99	4
FGFR1	93	4
ERBB2	83	4
PIK3CA	67	4
ALK	61	4
BRAF	48	4
ATM	35	4
CHEK2	30	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR, ERBB2, TP53
ERLOTINIB HYDROCHLORIDE	4	EGFR, ERBB2
CISPLATIN	4	EGFR
PONATINIB	4	BRAF, EGFR, ERBB2, FGFR1, KIT
AFATINIB	4	EGFR, ERBB2
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR, ERBB2
VEMURAFENIB	4	ARAF, BRAF, EGFR, KRAS
FEDRATINIB	4	ALK, BRAF, EGFR, FGFR1, KIT, PIK3CA
AXITINIB	4	EGFR, FGFR1, KIT
SORAFENIB	4	ARAF, BRAF, EGFR, ERBB2, FGFR1, KIT
DASATINIB ANHYDROUS	4	BRAF, EGFR, KIT
NICLOSAMIDE	4	EGFR, FGFR1, KIT, TP53
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	ALK, EGFR
NERATINIB	4	CHEK2, EGFR, ERBB2, MAP2K7
IBRUTINIB	4	EGFR, ERBB2
AFATINIB DIMALEATE	4	EGFR, ERBB2
CABOZANTINIB	4	EGFR, ERBB2, FGFR1, KIT, SLTM
DACOMITINIB	4	EGFR, ERBB2
DACOMITINIB ANHYDROUS	4	EGFR, ERBB2
CERITINIB	4	ALK, EGFR, KIT
VANDETANIB	4	ALK, EGFR, ERBB2, FGFR1, KIT
TRIBROMSALAN	4	EGFR, ERBB2
BOSUTINIB	4	ALK, CHEK2, EGFR, ERBB2, KIT, MAP2K7
BITHIONOL	4	EGFR, ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 19.

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
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
ALK	1,815	Binding:1801, Functional:13, ADMET:1
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
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
NFE2L2	861	Binding:812, Functional:49
CHEK2	690	Binding:687, Functional:2, ADMET:1
HRH4	483	Binding:348, Functional:133, ADMET:2
CHRNB4	407	Binding:309, Functional:96, ADMET:2
NQO1	279	Binding:227, ADMET:48, Functional:4
ATM	240	Binding:233, Functional:5, ADMET:2
MAP2K7	217	Binding:217
CASP8	116	Binding:106, Functional:10
ARAF	92	Binding:92
GRIK1	70	Binding:55, Functional:15
SMAD3	24	Binding:18, Functional:6
BMP2	22	Binding:18, Functional:4
SLC19A1	18	Binding:18
SLTM	14	Binding:14
BRCA1	13	Binding:9, Functional:4
KMT2D	11	Binding:11
PDCD4	8	Binding:8
SMAD4	6	Binding:6
FASLG	2	Binding:2
MAP7	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
CMTR2	2.1.1.296	methyltransferase cap2
NQO1	1.6.5.2	NAD(P)H dehydrogenase (quinone)
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
KIT	2.7.10.1	receptor protein-tyrosine kinase
ARAF	2.7.10.2	non-specific protein-tyrosine kinase
MAP2K7	2.7.12.2	mitogen-activated protein kinase kinase
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
CASP8	3.4.22.61	caspase-8
CHEK2	2.7.11.1	non-specific serine/threonine protein kinase
ATP8B1	7.6.2.1	P-type phospholipid transporter
ALK	2.7.10.1	receptor protein-tyrosine kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
PRKN	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase
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
BARD1	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EGFR	6,531
ERBB2	1,221
KRAS	861
TP53	869
CHRNB4	407
NQO1	279
FGFR1	1,465
KIT	2,305
MAP2K7	217
BRAF	1,442
CASP8	116
CHEK2	690
HRH4	483
ALK	1,815
NFE2L2	861
ATM	240
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 40; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

28 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)
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR, ERBB2, TP53
ERLOTINIB HYDROCHLORIDE	4	EGFR, ERBB2
PONATINIB	4	BRAF, EGFR, ERBB2, FGFR1, KIT
AFATINIB	4	EGFR, ERBB2
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR, ERBB2
VEMURAFENIB	4	ARAF, BRAF, EGFR, KRAS
FEDRATINIB	4	ALK, BRAF, EGFR, FGFR1, KIT, PIK3CA
AXITINIB	4	EGFR, FGFR1, KIT
SORAFENIB	4	ARAF, BRAF, EGFR, ERBB2, FGFR1, KIT
DASATINIB ANHYDROUS	4	BRAF, EGFR, KIT
NICLOSAMIDE	4	EGFR, FGFR1, KIT, TP53
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
NERATINIB	4	CHEK2, EGFR, ERBB2, MAP2K7
IBRUTINIB	4	EGFR, ERBB2
AFATINIB DIMALEATE	4	EGFR, ERBB2
CABOZANTINIB	4	EGFR, ERBB2, FGFR1, KIT, SLTM
DACOMITINIB	4	EGFR, ERBB2
DACOMITINIB ANHYDROUS	4	EGFR, ERBB2
CERITINIB	4	ALK, EGFR, KIT
VANDETANIB	4	ALK, EGFR, ERBB2, FGFR1, KIT
TRIBROMSALAN	4	EGFR, ERBB2
BOSUTINIB	4	ALK, CHEK2, EGFR, ERBB2, KIT, MAP2K7
BITHIONOL	4	EGFR, ERBB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	23	EGFR, ERBB2, KRAS, TP53, CHRNB4, SLTM, NQO1, FGFR1, KIT, ARAF (+13 more)
B	Phased (≥1) drug, not yet approved	1	GRIK1
C	Druggable family + PDB, no drug	1	CSMD1
D	Druggable family + AlphaFold only, no drug	1	CMTR2
E	Difficult family or no structure, no drug	19	ETV4, BMP2, FASLG, ZRANB1, PALB2, ERCC6, ATP8B1, EGFR-AS1, TNPO1-DT, MIR4675 (+9 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PALB2	0	BRCA1
CMTR2	0	—
ETV4	0	—
BMP2	22	—
FASLG	2	—
CSMD1	0	—
ZRANB1	0	—
ERCC6	0	—
ATP8B1	0	—
EGFR-AS1	0	—
TNPO1-DT	0	—
MIR4675	0	—
LINC01377	0	—
LINC02039	0	—
SMAD4	6	—
SMAD9	0	—
MAP7	1	—
MLH1	0	—
KMT2D	11	—
PRKN	0	—
BARD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3,711.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	651
PHASE3	212
PHASE1/PHASE2	170
PHASE4	37
PHASE2/PHASE3	30

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05463913	PHASE4	RECRUITING	Lung Nodule Detection Using Ultra-long FOV PET/CT
NCT05521789	PHASE4	RECRUITING	Erector Spinae Block for Thoracic Surgery
NCT05525338	PHASE4	RECRUITING	Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
NCT05663242	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Lung Tumors and Its Mechanism of Action
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06105801	PHASE4	RECRUITING	EBUS-TBNA vs Transbronchial Mediastinal Cryobiopsy for Adequacy of Next Generation Sequencing
NCT06276933	PHASE4	NOT_YET_RECRUITING	A Study of Camrelizumab Combined With Chemotherapy ± Thalidomide in First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
NCT06646471	PHASE4	RECRUITING	PROspective Master-protocol for Evaluation of Systemic THErapeutics in Elderly With Thoracic Malignancies
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00440960	PHASE4	COMPLETED	Anesthesia in Flexible Bronchoscopy for Lung Cancer Diagnostic
NCT00492843	PHASE4	TERMINATED	Loading Dose or Standard Dose of Intravenous Ibandronate in Treating Patients With Lung Cancer and Skeletal Metastasis
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00675168	PHASE4	UNKNOWN	Positron Emission Tomography (PET)/Computed Tomography (CT) and Roentgen in Lung Cancer: Evaluation of Patients in General Practice
NCT00712647	PHASE4	COMPLETED	Carotene and Retinol Efficacy Trial
NCT00747773	PHASE4	COMPLETED	Cryospray Ablation of Surgical Resection Specimens To Determine Safety And Histological Effect In The Lung
NCT01060137	PHASE4	COMPLETED	Fentanyl Matrix in Lung Cancer Pain
NCT01381627	PHASE4	UNKNOWN	Safety Evaluation of Dexmedetomidine for EBUS-TBNA
NCT01741506	PHASE4	COMPLETED	Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer
NCT02246023	PHASE4	COMPLETED	Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy
NCT02275702	PHASE4	COMPLETED	Randomized Study of Preoperative Dexamethasone for Quality of Recovery in VATS Lung Resection Patients
NCT02346318	PHASE4	UNKNOWN	The Randomized Controlled Clinical Trial of Kushen Injection
NCT02476526	PHASE4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02490059	PHASE4	COMPLETED	Ultrathin Bronchoscopy for Solitary Pulmonary Nodules
NCT02504801	PHASE4	UNKNOWN	Efficacy of Nebulized Pulmicort Respules in Primary Lung Cancer Patients With COPD
NCT02869789	PHASE4	COMPLETED	An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers
NCT03302221	PHASE4	WITHDRAWN	Regional Haemodynamic Changes in Radial Artery Assessment With Continuous Pulsed-wave Doppler Ultrasound
NCT03313544	PHASE4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03394222	PHASE4	COMPLETED	Effect of Preoperative Budesonide Inhalation on Arterial Blood Oxygenation and Intrapulmonary Shunt During OLV
NCT03570645	PHASE4	COMPLETED	Comparison of the Duration of Ropivacaine Combined With Dexmedetomidine or Dexamethasone on Paravertebral Block
NCT03571126	PHASE4	UNKNOWN	Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy of Lung Cancer
NCT03642457	PHASE4	TERMINATED	Efficacy Between Serratus Plane Block And Local Infiltration In Vats
NCT04145570	PHASE4	COMPLETED	A Single-Dose,ComparativeBioavailability Study ofTwo Formulations ofErlotinib150mgTabletsunderFastingConditions
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04613284	PHASE4	UNKNOWN	Rh-Endostatin Combined With CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC
NCT01394679	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study of 99mTC-EC-DG SPECT/CT Versus PET/CT in Lung Cancer
NCT03390686	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity of HD204 to Avastin® in Advanced Non-squamous Non-small Cell Lung Cancer Patients
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PACLITAXEL	4	132
VINORELBINE	4	34
DOCETAXEL ANHYDROUS	4	26
GEMCITABINE	4	25
CARBOPLATIN	4	24
CISPLATIN	4	18
TOPOTECAN HYDROCHLORIDE	4	15
AMIFOSTINE	4	10
ETOPOSIDE	4	10
FLUDEOXYGLUCOSE F 18	4	9
GEFITINIB	4	9
NIVOLUMAB	4	8
VINBLASTINE SULFATE	4	6
IFOSFAMIDE	4	5
MITOMYCIN	4	5
PEGFILGRASTIM	4	5
DOXORUBICIN HYDROCHLORIDE	4	4
ERLOTINIB	4	4
ISOTRETINOIN	4	4
BUPROPION HYDROCHLORIDE	4	3
DALTEPARIN SODIUM	4	3
DEXMEDETOMIDINE	4	3
EPOETIN ALFA	4	3
NICOTINE	4	3
ALECTINIB	4	2
EPIRUBICIN HYDROCHLORIDE	4	2
ETOPOSIDE PHOSPHATE	4	2
FILGRASTIM	4	2
THALIDOMIDE	4	2
VINCRISTINE SULFATE	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 31 predictive associations from 39 curated evidence items; also 10 oncogenic, 3 prognostic, 2 diagnostic, 1 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
EGFR Mutation	Gefitinib	Sensitivity/Response	CIViC B	EID2939
EGFR Mutation	Erlotinib	Sensitivity/Response	CIViC B	EID3864
KIF5B::RET Fusion	Selpercatinib	Sensitivity/Response	CIViC B	EID7067
PDCD4 EXPRESSION	Paclitaxel	Sensitivity/Response	CIViC B	EID821
KRAS G12D	Gefitinib	Resistance	CIViC B	EID2240 +4
KRAS G12D	Erlotinib	Resistance	CIViC B	EID3951 +4
KRAS G12	Gefitinib	Resistance	CIViC B	EID2938
KRAS G12A	Gefitinib	Resistance	CIViC B	EID2008
KRAS G12C	Gefitinib	Resistance	CIViC B	EID2257
KRAS G12S	Gefitinib	Resistance	CIViC B	EID2273
KRAS G12A	Erlotinib	Resistance	CIViC C	EID3712
KRAS G12V	Gefitinib	Resistance	CIViC C	EID2268
ROS1 D2033N	Crizotinib	Resistance	CIViC C	EID7685
MET Exon 14 Skipping Mutation	Capmatinib	Adverse Response	CIViC C	EID11459
ATM F858L	Selumetinib	Sensitivity/Response	CIViC D	EID5127
ATM Loss	Trametinib	Sensitivity/Response	CIViC D	EID5126
B2M High Expression	Anti-PD-L1 Monoclonal Antibody	Sensitivity/Response	CIViC D	EID12151
FGFR1 Amplification	Erdafitinib	Sensitivity/Response	CIViC D	EID7954
FGFR1 Expression	Ponatinib	Sensitivity/Response	CIViC D	EID681
FGFR1 Overexpression	Docetaxel + Rogaratinib	Sensitivity/Response	CIViC D	EID7831
NQO1 P187S	Amrubicin	Sensitivity/Response	CIViC D	EID941
CIC Loss	Trametinib	Resistance	CIViC D	EID5109
CIC Loss	Vemurafenib	Resistance	CIViC D	EID5110
CIC Loss	Selumetinib	Resistance	CIViC D	EID5116
EGFR T790M	Gefitinib + Multikinase Inhibitor AEE788	Resistance	CIViC D	EID642
ERBB2 Amplification AND YES1 Amplification	Neratinib	Resistance	CIViC D	EID12096
ETV1 Overexpression	Trametinib	Resistance	CIViC D	EID5118
ETV4 Overexpression	Trametinib	Resistance	CIViC D	EID5121
ETV5 Overexpression	Trametinib	Resistance	CIViC D	EID5122
NQO1 EXPRESSION	Amrubicin	Resistance	CIViC D	EID940

+1 more predictive associations (showing top 30 by evidence level).