Squamous cell lung carcinoma

Summary

Squamous cell lung carcinoma (MONDO:0005097) is a cancer with 75 cohort genes (385 GWAS associations across 17 studies; 17 CIViC-evidence somatic drivers; 61 ClinVar predisposition records) and 112 clinical trials. The dominant Reactome pathway is RAF/MAP kinase cascade (12 cohort genes). Molecularly, NFE2L2 Mutation confers sensitivity to Sapanisertib in Lung Squamous Cell Carcinoma (CIViC Level B); 12 further subtype–drug associations are mapped below. Top therapeutic interventions include docetaxel anhydrous, gefitinib, and carboplatin.

At a glance

• Classification: Cancer
• Cohort genes: 75
• GWAS associations: 385
• ClinVar variants: 61
• Clinical trials: 112
• Precision-medicine evidence (CIViC): 13 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	squamous cell lung carcinoma
Mondo ID	MONDO:0005097
EFO	EFO:0000708
DOID	DOID:3907
NCIT	C3493
SNOMED CT	254634000
UMLS	C0149782
MedGen	56202
Anatomy (UBERON)	UBERON:0002048
Is cancer (heuristic)	yes

Also known as: epidermoid cell carcinoma of lung · epidermoid cell carcinoma of the lung · epidermoid cell lung carcinoma · lung squamous cell carcinoma · squamous cell carcinoma of lung · squamous cell carcinoma of the lung · squamous cell lung cancer · squamous cell lung carcinoma

Data availability: 61 ClinVar variants · 385 GWAS associations (17 studies) · 200 cell lines · 77 intOGen driver records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › epithelial neoplasm › squamous cell neoplasm › squamous cell carcinoma › squamous cell lung carcinoma

Related subtypes (38): bone squamous cell carcinoma, prostate squamous cell carcinoma, trachea squamous cell carcinoma, scrotum squamous cell carcinoma, skin squamous cell carcinoma, bladder squamous cell carcinoma, urethra squamous cell carcinoma, papillary squamous carcinoma, basaloid squamous cell carcinoma, pseudoglandular squamous cell carcinoma, thymus squamous cell carcinoma, ovarian squamous cell carcinoma, renal pelvis squamous cell carcinoma, ureter squamous cell carcinoma, fallopian tube squamous cell carcinoma, squamous carcinoma in situ, keratinizing squamous cell carcinoma, esophageal squamous cell carcinoma, squamous cell breast carcinoma, adenosquamous carcinoma, cervical squamous cell carcinoma, colorectal squamous cell carcinoma, endometrial squamous cell carcinoma, gallbladder squamous cell carcinoma, gastric squamous cell carcinoma, thyroid gland squamous cell carcinoma, vaginal squamous cell carcinoma, head and neck squamous cell carcinoma, squamous cell carcinoma of the corpus uteri, squamous cell carcinoma of penis, squamous cell carcinoma of the small intestine, squamous cell carcinoma of pancreas, squamous cell carcinoma of liver and intrahepatic biliary tract, human papillomavirus-related squamous cell carcinoma, sarcomatoid squamous cell carcinoma, vulvar squamous cell carcinoma, metastatic squamous cell carcinoma, pure squamous carcinoma of the urothelial tract

Subtypes (2): lung occult squamous cell carcinoma, non-small cell squamous lung carcinoma

Genetics & variants

GWAS landscape

385 GWAS associations across 17 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs55781567	2e-74	CHRNA5	C	0.77
rs8040868	3e-41	CHRNA3	C	1.29
rs459961	1e-37	CLPTM1L	A	0.84
rs11200014	8e-35	FGFR2	A
rs31487	4e-30	CLPTM1L	?	0.19
rs9267123	5e-29	LINC01149 - HCP5	C	1.3
rs467095	2e-28	CLPTM1L	C	0.84
rs12601991	7e-28	HNF1B	T
rs11571818	4e-25	BRCA2	T	0.5
rs3131856	3e-23	SUMO2P1 - MOG	T	0.79
rs56113850	6e-21	CYP2A6	T	0.87
chr15:78618839	4e-20		C	0.26
rs3813565	3e-19	GOLGA6GP, CHRNB4	T	1.2
rs116822326	4e-19	HCP5	G	1.25
rs10757272	6e-19	CDKN2B-AS1	?	0.97
rs17879961	3e-18	CHEK2	A	2.59
rs465498	6e-18	CLPTM1L	A	1.21
rs139789464	8e-18	APOM	G	1.3
rs7953330	8e-18	WNK1	C	0.88
rs139285835	3e-17	SNHG32 - NEU1	T	1.31
rs74942078	3e-17	HLA-DQA1	T	1.27
rs62329683	3e-17	TERT - MIR4457	?	1.03
rs144433536	1e-16	TNXB	T	1.29
rs114274879	3e-16	VARS2	T	1.28
rs116725014	6e-16	MUC22	A	1.27
rs73110464	2e-15	KRT8	T
rs114665747	3e-15	NOTCH4 - TSBP1-AS1	T	1.28
rs115390513	4e-15	HCG27	C	1.26
rs114937304	6e-15	TSBP1-AS1	T	1.28
rs147680653	1e-14	HLA-F-AS1	G	1.32

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90455520	Gorman BR	2024	8,901	64,477	Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.
GCST90455523	Gorman BR	2024	8,901	64,477	Multi-ancestry GWAS meta-analyses of lung cancer reveal susceptibility loci and elucidate smoking-independent genetic risk.
GCST012200	Qin N	2020	8,350	27,355	Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma.
GCST90570630	You D	2025	7,426	162,770	A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases.
GCST90570631	You D	2025	7,426	495,288	A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases.
GCST004750	McKay JD	2017	7,426	55,627	Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.
GCST90134663	Byun J	2022	6,107	23,173	Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.
GCST003587	Fehringer G	2016	5,020	61,820	Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
GCST003588	Fehringer G	2016	5,020	61,820	Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.
GCST008835	Dai J	2019	3,860	13,328	Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	7
Tier 3: regulatory	1
Tier 4: intronic/intergenic	40

MAF distribution

Bucket	Variants
common (>=0.05)	44
low_freq (0.01-0.05)	3
rare (<0.01)	1
unknown	2

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	8
5_prime_UTR_variant	3
synonymous_variant	2
3_prime_UTR_variant	2
splice_polypyrimidine_tract_variant	1
unknown	1
splice_region_variant	1
missense_variant	1
regulatory_region_variant	1
stop_gained	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs55781567	15	78565644	C>G	0.347	5_prime_UTR_variant	CHRNA5	2e-74	Tier 2: splice/UTR
rs8040868	15	78618839	T>A,C	0.414	synonymous_variant	CHRNA3	3e-41	Tier 4: intronic/intergenic
rs459961	5	1336991	T>A	0.445	intron_variant	CLPTM1L	1e-37	Tier 4: intronic/intergenic
rs11200014	10	121575416	G>A,T	0.05	intron_variant	FGFR2	8e-35	Tier 4: intronic/intergenic
rs31487	5	1340986	G>A,C	0.05	intron_variant	CLPTM1L	4e-30	Tier 4: intronic/intergenic
rs9267123	6	31459618	G>C	0.123	intron_variant	LINC01149 - HCP5	5e-29	Tier 4: intronic/intergenic
rs467095	5	1336106	T>C	0.428	intron_variant	CLPTM1L	2e-28	Tier 4: intronic/intergenic
rs12601991	17	37741642	T>A,G	0.05	intron_variant	HNF1B	7e-28	Tier 4: intronic/intergenic
rs11571818	13	32394673	T>A,C	0.01	splice_polypyrimidine_tract_variant	BRCA2	4e-25	Tier 2: splice/UTR
rs3131856	6	29639324	T>C	0.085	intron_variant	SUMO2P1 - MOG	3e-23	Tier 4: intronic/intergenic
rs56113850	19	40847202	T>C	0.451	intron_variant	CYP2A6	6e-21	Tier 4: intronic/intergenic
chr15:78618839				0.392			4e-20	Tier 4: intronic/intergenic
rs3813565	15	78727268	G>A,T	0.397	splice_region_variant	GOLGA6GP, CHRNB4	3e-19	Tier 2: splice/UTR
rs116822326	6	31466334		0.155	intron_variant	HCP5	4e-19	Tier 4: intronic/intergenic
rs10757272	9	22088261	C>T	0.05	intron_variant	CDKN2B-AS1	6e-19	Tier 4: intronic/intergenic
rs17879961	22	28725099	A>C,G,T	0.005	missense_variant	CHEK2	3e-18	Tier 1: coding
rs465498	5	1325688	A>C,G,T	0.05	intron_variant	CLPTM1L	6e-18	Tier 4: intronic/intergenic
rs139789464	6	31657087		0.097	intron_variant	APOM	8e-18	Tier 4: intronic/intergenic
rs7953330	12	889653	G>C	0.302	intron_variant	WNK1	8e-18	Tier 4: intronic/intergenic
rs139285835	6	31850331		0.094	intergenic_variant	SNHG32 - NEU1	3e-17	Tier 4: intronic/intergenic
rs74942078	6	32638107		0.111	intron_variant	HLA-DQA1	3e-17	Tier 4: intronic/intergenic
rs62329683	5	1298972	C>T	0.05	intergenic_variant	TERT - MIR4457	3e-17	Tier 4: intronic/intergenic
rs144433536	6	32067917		0.096	synonymous_variant	TNXB	1e-16	Tier 4: intronic/intergenic
rs114274879	6	30914638		0.111	5_prime_UTR_variant	VARS2	3e-16	Tier 2: splice/UTR
rs116725014	6	31018051		0.107	intron_variant	MUC22	6e-16	Tier 4: intronic/intergenic
rs73110464	12	52918828	C>A,T	0.05	intron_variant	KRT8	2e-15	Tier 4: intronic/intergenic
rs114665747	6	32231204		0.099	intergenic_variant	NOTCH4 - TSBP1-AS1	3e-15	Tier 4: intronic/intergenic
rs115390513	6	31208169		0.105	intron_variant	HCG27	4e-15	Tier 4: intronic/intergenic
rs114937304	6	32373094		0.102	intron_variant	TSBP1-AS1	6e-15	Tier 4: intronic/intergenic
rs147680653	6	29785031		0.082	intron_variant	HLA-F-AS1	1e-14	Tier 4: intronic/intergenic

ClinVar germline variants

61 retrieved; paginated sample, class counts are floors:

27 benign, 23 uncertain significance, 5 conflicting classifications of pathogenicity, 2 pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
142061	NM_000077.5(CDKN2A):c.47_50del (p.Leu16fs)	CDKN2A	Pathogenic	criteria provided, multiple submitters, no conflicts
16339	NM_000142.5(FGFR3):c.746C>G (p.Ser249Cys)	FGFR3	Pathogenic	criteria provided, multiple submitters, no conflicts
12579	NM_004985.5(KRAS):c.34G>C (p.Gly12Arg)	KRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
873163	NM_006218.4(PIK3CA):c.452T>C (p.Val151Ala)	PIK3CA	Likely pathogenic	no assertion criteria provided
820351	NM_000077.5(CDKN2A):c.194T>C (p.Leu65Pro)	CDKN2A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
560007	NM_005228.5(EGFR):c.2492G>A (p.Arg831His)	EGFR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
873178	NM_000142.5(FGFR3):c.1266+25C>T	FGFR3	Conflicting classifications of pathogenicity	no assertion criteria provided
873182	NM_000222.3(KIT):c.2597-51T>C	KIT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
134654	NM_000245.4(MET):c.1771C>T (p.Arg591Trp)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
873171	NM_004304.5(ALK):c.4165-19del	ALK	Uncertain significance	no assertion criteria provided
873172	NM_004304.5(ALK):c.3744-53del	ALK	Uncertain significance	no assertion criteria provided
873173	NM_004304.5(ALK):c.3451-35TCC[3]	ALK	Uncertain significance	no assertion criteria provided
419560	NM_000077.5(CDKN2A):c.292C>T (p.His98Tyr)	CDKN2A	Uncertain significance	criteria provided, multiple submitters, no conflicts
873185	NM_058195.4(CDKN2A):c.194-3838A>G	CDKN2A	Uncertain significance	no assertion criteria provided
873166	NM_006182.4(DDR2):c.1099+20T>C	DDR2	Uncertain significance	no assertion criteria provided
873168	NM_006182.4(DDR2):c.2434-46TC[6]	DDR2	Uncertain significance	no assertion criteria provided
873169	NM_006182.4(DDR2):c.2434-46TC[7]	DDR2	Uncertain significance	no assertion criteria provided
873170	NM_006182.4(DDR2):c.2434-46TC[9]	DDR2	Uncertain significance	criteria provided, single submitter
873187	NM_000141.5(FGFR2):c.1986+23G>C	FGFR2	Uncertain significance	no assertion criteria provided
873179	NM_000142.5(FGFR3):c.1837-3C>T	FGFR3	Uncertain significance	no assertion criteria provided
873160	NM_003537.4(H3C2):c.*10C>T	H3C2	Uncertain significance	no assertion criteria provided
873161	NC_000006.12:g.26032121C>G	H3C2	Uncertain significance	no assertion criteria provided
873189	NM_005343.4(HRAS):c.450+38dup	HRAS	Uncertain significance	no assertion criteria provided
873190	NM_005343.4(HRAS):c.450+35A>C	HRAS	Uncertain significance	no assertion criteria provided
873191	NM_005343.4(HRAS):c.450+31A>G	HRAS	Uncertain significance	no assertion criteria provided
873192	NM_005343.4(HRAS):c.111+18G>C	HRAS	Uncertain significance	no assertion criteria provided
873193	NM_004985.5(KRAS):c.291-50A>G	KRAS	Uncertain significance	no assertion criteria provided
873183	NM_000245.4(MET):c.2265-118del	MET	Uncertain significance	no assertion criteria provided
873176	NM_006218.4(PIK3CA):c.562+40del	PIK3CA	Uncertain significance	no assertion criteria provided
873186	NM_000314.8(PTEN):c.634+14A>G	PTEN	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 133 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 4

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

Gene	HGNC	Evidence routes
FGFR2	FGFR2	GWAS, Orphanet
BRCA2	BRCA2	GWAS, Orphanet
TERT	TERT	GWAS, Orphanet
WWOX	WWOX	GWAS, Orphanet

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
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
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
PDGFRA	Act	CSCC,GB,GBM,HGGNOS,LGGNOS,LUSC,PAST	CIViC #38
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CD274	LoF	DLBCLNOS	CIViC #11335
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
NFE2L2	Act	BLCA,CESC,ESCA,HCC,HNSC,LUSC,NSCLC,PRCC,UCEC	CIViC #3878
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
STK11	LoF	ANSC,CEAD,CESC,CHOL,LUAD,NSCLC,WDTC	CIViC #5534
TERT	Act	PRCC	CIViC #79
WNK1			CIViC #14591
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
CDKN2B			CIViC #916
CHEK1			CIViC #981

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2
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
PDGFRA	Orphanet:168940	Chronic eosinophilic leukemia
PDGFRA	Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRA	Orphanet:199306	Cleft lip/palate
PDGFRA	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRA	Orphanet:44890	Gastrointestinal stromal tumor
PDGFRA	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
CCND1	Orphanet:29073	Multiple myeloma
CCND1	Orphanet:52416	Mantle cell lymphoma
CCND1	Orphanet:67038	B-cell chronic lymphocytic leukemia
CCND1	Orphanet:892	Von Hippel-Lindau disease
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome

Cohort genes → proteins

75 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	63
gwas_and_clinvar	1
civic_only	5
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	clinvar,civic_evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gwas,clinvar
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	clinvar,civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar,civic_evidence
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	clinvar,civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
CD274	HGNC:17635	ENSG00000120217	Q9NZQ7	Programmed cell death 1 ligand 1	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
NFE2L2	HGNC:7782	ENSG00000116044	Q16236	Nuclear factor erythroid 2-related factor 2	civic_evidence
XCL2	HGNC:10646	ENSG00000143185	Q9UBD3	Cytokine SCM-1 beta	gwas
SLC1A1	HGNC:10939	ENSG00000106688	P43005	Excitatory amino acid transporter 3	gwas
SLC1A6	HGNC:10944	ENSG00000105143	P48664	Excitatory amino acid transporter 4	gwas
SLC22A2	HGNC:10966	ENSG00000112499	O15244	Solute carrier family 22 member 2	gwas
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gwas
SPI1	HGNC:11241	ENSG00000066336	P17947	Transcription factor PU.1	gwas
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	clinvar
BTN3A2	HGNC:1139	ENSG00000186470	P78410	Butyrophilin subfamily 3 member A2	gwas
BTN3A3	HGNC:1140	ENSG00000111801	O00478	Butyrophilin subfamily 3 member A3	gwas
SYT4	HGNC:11512	ENSG00000132872	Q9H2B2	Synaptotagmin-4	gwas
TAC1	HGNC:11517	ENSG00000006128	P20366	Protachykinin-1	gwas
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
THRB	HGNC:11799	ENSG00000151090	P10828	Thyroid hormone receptor beta	gwas
TMEFF1	HGNC:11866	ENSG00000241697	Q8IYR6	Tomoregulin-1	gwas
TNXB	HGNC:11976	ENSG00000168477	P22105	Tenascin-X	gwas
VARS1	HGNC:12651	ENSG00000204394	P26640	Valine–tRNA ligase	gwas
VSNL1	HGNC:12722	ENSG00000163032	P62760	Visinin-like protein 1	gwas
WWOX	HGNC:12799	ENSG00000186153	Q9NZC7	WW domain-containing oxidoreductase	gwas
REXO4	HGNC:12820	ENSG00000148300	Q9GZR2	RNA exonuclease 4	gwas
XRCC4	HGNC:12831	ENSG00000152422	Q13426	DNA repair protein XRCC4	gwas
ZNF165	HGNC:12953	ENSG00000197279	P49910	Zinc finger protein 165	gwas
TRIM26	HGNC:12962	ENSG00000234127	Q12899	Tripartite motif-containing protein 26	gwas
ZNF184	HGNC:12975	ENSG00000096654	Q99676	Zinc finger protein 184	gwas
ZSCAN9	HGNC:12984	ENSG00000137185	O15535	Zinc finger and SCAN domain-containing protein 9	gwas
ZNF204P	HGNC:12995	ENSG00000204789		zinc finger protein 204, pseudogene	gwas
ZSCAN12	HGNC:13172	ENSG00000158691	O43309	Zinc finger and SCAN domain-containing protein 12	gwas
IKZF2	HGNC:13177	ENSG00000030419	Q9UKS7	Zinc finger protein Helios	gwas
POLR1H	HGNC:13182	ENSG00000066379	Q9P1U0	DNA-directed RNA polymerase I subunit RPA12	gwas
VN1R10P	HGNC:13550	ENSG00000220758		vomeronasal 1 receptor 10 pseudogene	gwas
HIVEP3	HGNC:13561	ENSG00000127124	Q5T1R4	Transcription factor HIVEP3	gwas
SNTG2	HGNC:13741	ENSG00000172554	Q9NY99	Gamma-2-syntrophin	gwas
ZNF311	HGNC:13847	ENSG00000197935	Q5JNZ3	Zinc finger protein 311	gwas
SCAND3	HGNC:13851	ENSG00000232040	Q6R2W3	SCAN domain-containing protein 3	gwas
APOM	HGNC:13916	ENSG00000204444	O95445	Apolipoprotein M	gwas
TSBP1	HGNC:13922	ENSG00000204296	Q5SRN2	Testis-expressed basic protein 1	gwas
OR2B2	HGNC:13966	ENSG00000168131	Q9GZK3	Olfactory receptor 2B2	gwas
OR14J1	HGNC:13971	ENSG00000204695	Q9UGF5	Olfactory receptor 14J1	gwas
ZNF322P1	HGNC:14003	ENSG00000188801		zinc finger protein 322 pseudogene 1	gwas
ELAC2	HGNC:14198	ENSG00000006744	Q9BQ52	Zinc phosphodiesterase ELAC protein 2	gwas

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.
FGFR2	Fibroblast growth factor receptor 2	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, migration and apoptosis, and in the regulation of embryonic de…
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.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
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.
CD274	Programmed cell death 1 ligand 1	Plays a critical role in induction and maintenance of immune tolerance to self.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
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.
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…
XCL2	Cytokine SCM-1 beta	Chemotactic activity for lymphocytes but not for monocytes or neutrophils.
SLC1A1	Excitatory amino acid transporter 3	Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.
SLC1A6	Excitatory amino acid transporter 4	Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.
SLC22A2	Solute carrier family 22 member 2	Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SPI1	Transcription factor PU.1	Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites.
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
BTN3A2	Butyrophilin subfamily 3 member A2	Plays a role in T-cell responses in the adaptive immune response.
BTN3A3	Butyrophilin subfamily 3 member A3	Plays a role in T-cell responses in the adaptive immune response.
SYT4	Synaptotagmin-4	Synaptotagmin family member which does not bind Ca(2+).
TAC1	Protachykinin-1	Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles.
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3'.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
THRB	Thyroid hormone receptor beta	Nuclear hormone receptor that can act as a repressor or activator of transcription.
TMEFF1	Tomoregulin-1	Neuron-specific restriction factor that prevents herpes simplex virus 1 (HHV-1) infection in the brain by blocking viral entry.
TNXB	Tenascin-X	Appears to mediate interactions between cells and the extracellular matrix.
VARS1	Valine–tRNA ligase	Catalyzes the attachment of valine to tRNA(Val).
VSNL1	Visinin-like protein 1	Regulates (in vitro) the inhibition of rhodopsin phosphorylation in a calcium-dependent manner.
WWOX	WW domain-containing oxidoreductase	Putative oxidoreductase.
XRCC4	DNA repair protein XRCC4	DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination.
ZNF165	Zinc finger protein 165	May be involved in transcriptional regulation.
TRIM26	Tripartite motif-containing protein 26	E3 ubiquitin-protein ligase which regulates the IFN-beta production and antiviral response downstream of various DNA-encoded pattern-recognition receptors (PRRs).
ZNF184	Zinc finger protein 184	May be involved in transcriptional regulation.
ZSCAN9	Zinc finger and SCAN domain-containing protein 9	May be involved in transcriptional regulation.
ZSCAN12	Zinc finger and SCAN domain-containing protein 12	May be involved in transcriptional regulation.
IKZF2	Zinc finger protein Helios	Transcription factor, which stabilizes the noninflammatory phenotype of regulatory T cells (Tregs).
POLR1H	DNA-directed RNA polymerase I subunit RPA12	Core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates.
HIVEP3	Transcription factor HIVEP3	Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B motif of gene such as S100A4, involved in c…
SNTG2	Gamma-2-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of proteins.
ZNF311	Zinc finger protein 311	May be involved in transcriptional regulation.
APOM	Apolipoprotein M	Probably involved in lipid transport.
OR2B2	Olfactory receptor 2B2	Odorant receptor.
OR14J1	Olfactory receptor 14J1	Odorant receptor.
ELAC2	Zinc phosphodiesterase ELAC protein 2	Zinc phosphodiesterase, which displays mitochondrial tRNA 3’-processing endonuclease activity.
WNK1	Serine/threonine-protein kinase WNK1	Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx.
IPPK	Inositol-pentakisphosphate 2-kinase	Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate).
NBAS	NBAS subunit of NRZ tethering complex	Involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER.
RALY	RNA-binding protein Raly	RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver.
RAPGEF5	Rap guanine nucleotide exchange factor 5	Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP.
ERLIN1	Erlin-1	Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs).

Protein-family classification

Druggable: 25 · Difficult: 20 · Unknown: 30 · Druggable fraction: 0.33

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	10	3.7×	0.003
Transcription factor	14	1.5×	0.324
Antibody/Immunoglobulin	5	1.9×	0.381
Nuclear receptor	1	5.2×	0.443
Scaffold/PPI	6	1.4×	0.532
Ion channel	1	1.5×	0.777
Transporter	1	1.0×	0.777
GPCR	3	1.0×	0.777
Enzyme (other)	4	0.6×	0.979
Other/Unknown	30	0.7×	0.998

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
FGFR2	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
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CD274	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
NFE2L2	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
XCL2	Other/Unknown	no		Chemokine_IL8-like_dom, Chemokine_XCL1/XCL2, Interleukin_8-like_sf
SLC1A1	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf
SLC1A6	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf
SLC22A2	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SPI1	Other/Unknown	no		Ets_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
BTN3A2	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
BTN3A3	Antibody/Immunoglobulin	yes		B30.2/SPRY, Ig_sub, SPRY_dom
SYT4	Other/Unknown	no		C2_dom, Synaptotagmin, C2_domain_sf
TAC1	Other/Unknown	no		Tachykinin_dom, Tachykinin_fam, Tachy_Neuro_lke_CS
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
THRB	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
TMEFF1	Other/Unknown	no		EGF, Kazal_dom, Kazal_dom_sf
TNXB	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
VARS1	Enzyme (other)	yes	6.1.1.9	aa-tRNA-synth_I_CS, aa-tRNA-synth_Ia, Valyl-tRNA_ligase
VSNL1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
WWOX	Scaffold/PPI	no		WW_dom, SDR_fam, WW_dom_sf
REXO4	Other/Unknown	no		RNaseH-like_sf, Ribonucl_H, RNaseH_sf
XRCC4	Other/Unknown	no		XRCC4_N_sf, DNA_repair_prot_XRCC4, XRCC4-like_C
ZNF165	Transcription factor	no		SCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
TRIM26	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
ZNF184	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZSCAN9	Transcription factor	no		SCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
ZNF204P	Other/Unknown	no
ZSCAN12	Transcription factor	no		SCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
IKZF2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
POLR1H	Transcription factor	no		Znf_TFIIS, Rpa12/Rpb9/Rpc10/TFS, DNA-dir_RNA_pol-M_15_CS
VN1R10P	Other/Unknown	no
HIVEP3	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_HIVEP, Znf_C2H2_sf
SNTG2	Scaffold/PPI	no		PDZ, Syntrophin, PDZ_sf
ZNF311	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
SCAND3	Transcription factor	no		Integrase_cat-core, SCAN_dom, RNaseH-like_sf
APOM	Other/Unknown	no		Calycin, ApoM
TSBP1	Other/Unknown	no		TSBP1
OR2B2	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
OR14J1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
ZNF322P1	Other/Unknown	no
ELAC2	Enzyme (other)	yes	3.1.26.11	tRNase_Z_dom, RibonucZ/Hydroxyglut_hydro, RNZ2-like

Expression context

Cohort genes with no expression data: 0.

62 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	2
broad (>20)	72
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	9
granulocyte	7
ventricular zone	6
left testis	6
male germ line stem cell (sensu Vertebrata) in testis	5
right testis	5
Brodmann (1909) area 23	5
stromal cell of endometrium	4
calcaneal tendon	4
cerebellar cortex	4
secondary oocyte	4
leukocyte	4
cortical plate	4
endothelial cell	4
ganglionic eminence	4
oocyte	4
corpus callosum	3
tibia	3
sural nerve	3
buccal mucosa cell	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CD274	208	ubiquitous	marker	cartilage tissue, placenta, lower lobe of lung
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
NFE2L2	295	ubiquitous	marker	epithelium of nasopharynx, pharyngeal mucosa, oral cavity
XCL2	119	tissue_specific	marker	granulocyte, spleen, blood
SLC1A1	248	ubiquitous	marker	corpus epididymis, jejunal mucosa, ileal mucosa
SLC1A6	124	broad	marker	right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere
SLC22A2	108	tissue_specific	marker	adult mammalian kidney, nephron tubule, renal medulla
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SPI1	170	broad	marker	granulocyte, monocyte, leukocyte
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
BTN3A2	266	ubiquitous	marker	granulocyte, leukocyte, monocyte
BTN3A3	282	ubiquitous	marker	granulocyte, spleen, leukocyte
SYT4	171	broad	marker	cerebellar vermis, cortical plate, cerebellum
TAC1	214	broad	marker	dorsal root ganglion, lateral globus pallidus, endothelial cell
HNF1B	74	broad	marker	metanephros cortex, adult mammalian kidney, kidney
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
THRB	267	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, tibia
TMEFF1	86	ubiquitous	marker	cortical plate, ganglionic eminence, primordial germ cell in gonad
TNXB	134	ubiquitous	marker	apex of heart, right adrenal gland cortex, right adrenal gland
VARS1	134	ubiquitous	marker	right testis, left testis, testis
VSNL1	239	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, orbitofrontal cortex
WWOX	286	ubiquitous	marker	parotid gland, cervix squamous epithelium, cranial nerve II
REXO4	134	ubiquitous	yes	sural nerve, skeletal muscle tissue, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 21.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EGFR	18,421
KRAS	14,509
CDKN2A	9,311
CCND1	8,328
WWOX	5,892
VARS1	5,848
TERT	5,717
FGFR1	5,693
PDGFRA	5,186
STK11	5,146

Intra-cohort edges

A	B	Sources
BRCA2	CCND1	intact
BRCA2	STK11	string_interaction
BTN3A2	BTN3A3	biogrid_interaction, intact
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	CDKN2B	string_interaction
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	TMEFF1	intact
EGFR	PDGFRA	intact
FGFR1	FGFR2	intact
FGFR1	SLC1A1	biogrid_interaction
KRAS	STK11	string_interaction
LRP11	PDGFRA	intact
NDFIP1	SLC1A1	biogrid_interaction, intact
OR14J1	TSBP1	string_interaction
OR14J1	ZNF311	string_interaction
RALY	RIMS1	intact
RAPGEF5	WNK1	biogrid_interaction
SCGN	TAC1	string_interaction
SPI1	XCL2	intact
TNXB	TSBP1	string_interaction

Structural data

PDB: 42 · AlphaFold-only: 29 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
EGFR	P00533	388
CHEK1	O14757	164
FGFR1	P11362	83
CD274	Q9NZQ7	76
FGFR2	P21802	63
SPI1	P17947	35
XRCC4	Q13426	35
THRB	P10828	34
NFE2L2	Q16236	23
TERT	O14746	23
SLC1A1	P43005	22
BTN3A2	P78410	18
FGFR3	P22607	15
PDGFRA	P16234	15
BRCA2	P51587	14
TAC1	P20366	13
CCND1	P24385	11
MORF4L1	Q9UBU8	11
ELAC2	Q9BQ52	10
BTN3A3	O00478	9
IKZF2	Q9UKS7	7
POLR1H	Q9P1U0	7
WNK1	Q9H4A3	5
CDKN2A	P42771	5
KHDRBS3	O75525	5
STK11	Q15831	4
NPFFR1	Q9GZQ6	4
HNF1B	P35680	3
TNXB	P22105	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABHD2	P08910	91.06
CDKN2B	P42772	90.12
IPPK	Q9H8X2	88.72
VARS1	P26640	88.12
OR14J1	Q9UGF5	87.60
VSNL1	P62760	86.68
TRIM26	Q12899	83.49
XCL2	Q9UBD3	81.47
SLC1A6	P48664	80.35
OR2B2	Q9GZK3	79.53
NBAS	A2RRP1	74.42
ZNF184	Q99676	72.56
SCAND3	Q6R2W3	72.39
REXO4	Q9GZR2	71.20
NEK10	Q6ZWH5	70.23
ZSCAN12	O43309	70.20
CATSPER2	Q96P56	69.83
TMEFF1	Q8IYR6	69.30
NRSN1	Q8IZ57	69.20
LRP11	Q86VZ4	68.15
DAB2IP	Q5VWQ8	65.74
ZNF311	Q5JNZ3	65.02
ZSCAN9	O15535	64.00
NDFIP1	Q9BT67	63.27
ZNF165	P49910	58.79
NPAS3	Q8IXF0	56.50
SLTM	Q9NWH9	52.38
TSBP1	Q5SRN2	45.58
HIVEP3	Q5T1R4	37.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 750. Enrichment computed across 198 evidence-associated genes (122 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 122 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	12	6.0×	5e-04	EGFR, FGFR2, FGFR3, KRAS, PDGFRA, FGFR1, HRAS, KIT (+4 more)
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	4	28.8×	0.001	KRAS, PDGFRA, HRAS, PIK3CA
Signaling by PDGFRA extracellular domain mutants	4	28.8×	0.001	KRAS, PDGFRA, HRAS, PIK3CA
Signaling by SCF-KIT	6	12.2×	0.001	KRAS, CHEK1, SH2B3, HRAS, KIT, PIK3CA
Constitutive Signaling by Aberrant PI3K in Cancer	8	8.3×	0.001	EGFR, FGFR2, FGFR3, PDGFRA, FGFR1, KIT, MET, PIK3CA
Constitutive Signaling by EGFRvIII	4	23.4×	0.003	EGFR, KRAS, HRAS, PIK3CA
Signaling by ERBB2 ECD mutants	4	22.0×	0.003	EGFR, KRAS, HRAS, PIK3CA
RAS signaling downstream of NF1 loss-of-function variants	3	40.1×	0.003	KRAS, HRAS, NF1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	8	6.3×	0.003	EGFR, FGFR2, FGFR3, PDGFRA, FGFR1, KIT, MET, PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	4	18.7×	0.004	EGFR, KRAS, HRAS, PIK3CA
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	4	17.0×	0.005	KRAS, HRAS, KIT, PIK3CA
Signaling by FGFR3 in disease	4	16.3×	0.006	FGFR3, KRAS, HRAS, PIK3CA
EGFR Transactivation by Gastrin	3	28.1×	0.007	EGFR, KRAS, HRAS
RUNX3 regulates p14-ARF	3	28.1×	0.007	KRAS, CCND1, CDKN2A
Endosomal/Vacuolar pathway	3	25.5×	0.008	HLA-A, HLA-C, HLA-E
MET activates RAS signaling	3	25.5×	0.008	KRAS, HRAS, MET
Signaling by ERBB2 KD Mutants	4	13.9×	0.008	EGFR, KRAS, HRAS, PIK3CA
Signaling by FGFR4 in disease	3	23.4×	0.010	KRAS, HRAS, PIK3CA
Downstream signal transduction	4	12.5×	0.011	KRAS, PDGFRA, HRAS, PIK3CA
Signaling by RAS GAP mutants	2	62.4×	0.011	KRAS, HRAS
Signaling by RAS GTPase mutants	2	62.4×	0.011	KRAS, HRAS
DAP12 signaling	4	12.1×	0.011	KRAS, HLA-E, HRAS, PIK3CA
FLT3 Signaling	4	11.3×	0.013	KRAS, SH2B3, HRAS, PIK3CA
Interferon gamma signaling	6	6.2×	0.013	TRIM26, HLA-A, HLA-C, HLA-DQA1, HLA-DQB2, HLA-E
GRB2 events in EGFR signaling	3	18.7×	0.014	EGFR, KRAS, HRAS
Signaling by FLT3 ITD and TKD mutants	3	18.7×	0.014	KRAS, HRAS, PIK3CA
PIP3 activates AKT signaling	8	4.4×	0.014	EGFR, FGFR2, FGFR3, PDGFRA, FGFR1, KIT, MET, PIK3CA
SHC1 events in EGFR signaling	3	17.6×	0.016	EGFR, KRAS, HRAS
Signaling by FGFR1 in disease	4	9.6×	0.020	KRAS, FGFR1, HRAS, PIK3CA
GRB2 events in ERBB2 signaling	3	15.6×	0.021	EGFR, KRAS, HRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 160 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 phospholipase activity	3	63.2×	0.008	FGFR2, FGFR3, FGFR1
peptide antigen assembly with MHC class II protein complex	4	26.3×	0.008	HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DQB2
positive regulation of dendrite development	4	24.8×	0.008	DAB2IP, COBL, EZH2, ALK
oncogene-induced cell senescence	3	45.1×	0.011	SPI1, CDKN2A, HRAS
positive regulation of CD8-positive, alpha-beta T cell activation	2	105.3×	0.018	HLA-A, HLA-E
endochondral bone growth	3	31.6×	0.018	FGFR2, FGFR3, DDR2
T cell receptor signaling pathway	7	6.6×	0.018	STK11, BTN3A2, BTN3A3, WNK1, HLA-A, HRAS, PIK3CA
positive regulation of cell population proliferation	15	3.1×	0.018	EGFR, FGFR2, FGFR3, PDGFRA, TNXB, CDCA7L, EDN2, ESM1 (+7 more)
protein autophosphorylation	7	6.4×	0.020	FGFR2, PDGFRA, STK11, DDR2, FGFR1, ALK, KIT
forebrain astrocyte development	2	70.2×	0.024	KRAS, NF1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	2	70.2×	0.024	FGFR2, FGFR1
positive regulation of CD8-positive, alpha-beta T cell proliferation	2	70.2×	0.024	HLA-A, HLA-E
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	3	24.3×	0.024	HLA-A, HLA-C, HLA-E
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	3	24.3×	0.024	HLA-A, HLA-C, HLA-E
antigen processing and presentation of exogenous peptide antigen via MHC class II	4	13.6×	0.024	HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DQB2
digestive tract development	4	13.2×	0.024	FGFR2, COBL, KIT, NFE2L2
cellular senescence	5	9.2×	0.024	BRCA2, CDKN2A, CDKN2B, HRAS, MAP2K1
ventricular zone neuroblast division	2	52.7×	0.025	FGFR2, FGFR1
CD8-positive, alpha-beta T cell activation	2	52.7×	0.025	HLA-A, HLA-E
synaptic transmission involved in micturition	2	52.7×	0.025	CHRNA3, CHRNB4
response to UV-A	2	52.7×	0.025	EGFR, CCND1
negative regulation of hydrogen peroxide-mediated programmed cell death	2	52.7×	0.025	DDR2, MET
vasculature development	3	21.1×	0.025	STK11, NOTCH4, PIK3CA
maternal behavior	3	21.1×	0.025	DBH, HCN1, PTEN
Schwann cell development	3	19.8×	0.025	HRAS, MAP2K1, NF1
T cell mediated immunity	3	18.6×	0.025	BTN3A2, BTN3A3, GNL1
regulation of long-term neuronal synaptic plasticity	3	18.6×	0.025	KRAS, HRAS, NF1
replicative senescence	3	18.6×	0.025	TERT, CDKN2A, CHEK1
positive regulation of immune response	4	12.0×	0.025	HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DQB2
adult behavior	4	11.7×	0.025	SLC1A1, SLITRK1, ALK, PTEN

Therapeutics

Drugs indicated for this disease

2 approved, 15 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cetuximab	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Camrelizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Gefitinib	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Iniparib	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
Palbociclib	Phase 3 (in late-stage trials)
Pelareorep	Phase 3 (in late-stage trials)
Penpulimab	Phase 3 (in late-stage trials)
Tremelimumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bevacizumab, Clarithromycin, Dasatinib Anhydrous, Dexamethasone, Erdafitinib, Icotinib, Necitumumab, Nintedanib, Pemetrexed, Pioglitazone, Ramucirumab, Rigosertib, Rilotumumab, Selinexor, Selumetinib, Sintilimab, Talazoparib, Taselisib, Telisotuzumab Vedotin, Tislelizumab, Treosulfan.

Drug target analysis

Approved (phase 4): 15 · Phase ≥3: 18 · Phased (≥1): 18 · Undrugged: 57

Druggability breadth: 73 of 198 evidence-associated genes (37%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

Symbol	Example approved molecule
EGFR	LEVODOPA
FGFR2	PONATINIB
FGFR3	PONATINIB
KRAS	VEMURAFENIB
PDGFRA	PONATINIB
CCND1	PALBOCICLIB
CD274	MOCLOBEMIDE
SLTM	CABOZANTINIB
FGFR1	PONATINIB
NFE2L2	DIMETHYL FUMARATE
SLC22A2	PROGESTERONE
STK11	FEDRATINIB
TERT	BERBERINE
THRB	AMINOCAPROIC ACID
CHEK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EGFR	175	4
THRB	117	4
FGFR1	93	4
PDGFRA	77	4
FGFR3	64	4
FGFR2	59	4
SLC22A2	47	4
CHEK1	36	4
CCND1	35	4
STK11	17	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR
ERLOTINIB HYDROCHLORIDE	4	EGFR
CISPLATIN	4	EGFR
PONATINIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
AFATINIB	4	EGFR
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR
VEMURAFENIB	4	EGFR, KRAS
FEDRATINIB	4	CHEK1, EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
AXITINIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
SORAFENIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR, FGFR1
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	EGFR
NERATINIB	4	CHEK1, EGFR
IBRUTINIB	4	EGFR, FGFR2
AFATINIB DIMALEATE	4	EGFR
CABOZANTINIB	4	EGFR, FGFR1, SLTM
DACOMITINIB	4	EGFR
DACOMITINIB ANHYDROUS	4	EGFR
CERITINIB	4	EGFR, FGFR2, FGFR3, PDGFRA
VANDETANIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
TRIBROMSALAN	4	EGFR
BOSUTINIB	4	CHEK1, EGFR, PDGFRA
BITHIONOL	4	EGFR, SLC22A2, THRB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
CHEK1	1,086	Binding:1039, Functional:44, ADMET:3
FGFR3	975	Binding:948, Functional:18, ADMET:9
FGFR2	966	Binding:940, Functional:22, ADMET:4
KRAS	861	Binding:829, Functional:32
NFE2L2	861	Binding:812, Functional:49
CCND1	576	Binding:574, Functional:1, ADMET:1
CD274	525	Binding:520, Functional:5
TERT	391	Binding:389, Functional:2
STK11	244	Binding:244
THRB	169	Binding:129, Functional:40
WNK1	165	Binding:165
NPFFR1	114	Functional:68, Binding:46
SLC22A2	101	Functional:62, ADMET:21, Binding:18
SLC1A1	50	Binding:43, Functional:7
MASTL	44	Binding:44
NEK10	40	Binding:40
IKZF2	26	Binding:26
SLTM	14	Binding:14
DAB2IP	8	Binding:8
VARS1	7	Binding:7
MORF4L1	2	Binding:2
CDKN2A	2	Binding:2
XRCC4	1	Binding:1
NBAS	1	Binding:1
ERLIN1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
VARS1	6.1.1.9	valine-tRNA ligase
ELAC2	3.1.26.11	tRNase Z
IPPK	2.7.1.158	inositol-pentakisphosphate 2-kinase
CHEK1	2.7.11.1	non-specific serine/threonine protein kinase

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
FGFR2	966
FGFR3	975
KRAS	861
PDGFRA	1,172
CCND1	576
CD274	525
FGFR1	1,465
NFE2L2	861
SLC22A2	101
STK11	244
TERT	391
THRB	169
WNK1	165
NPFFR1	114
CHEK1	1,086

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

27 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR
CISPLATIN	4	EGFR
PONATINIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR
VEMURAFENIB	4	EGFR, KRAS
FEDRATINIB	4	CHEK1, EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
AXITINIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
SORAFENIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR, FGFR1
TERFENADINE	4	EGFR
ALECTINIB	4	EGFR
NERATINIB	4	CHEK1, EGFR
IBRUTINIB	4	EGFR, FGFR2
AFATINIB DIMALEATE	4	EGFR
CABOZANTINIB	4	EGFR, FGFR1, SLTM
DACOMITINIB	4	EGFR
DACOMITINIB ANHYDROUS	4	EGFR
CERITINIB	4	EGFR, FGFR2, FGFR3, PDGFRA
VANDETANIB	4	EGFR, FGFR1, FGFR2, FGFR3, PDGFRA
TRIBROMSALAN	4	EGFR
BOSUTINIB	4	CHEK1, EGFR, PDGFRA
BITHIONOL	4	EGFR, SLC22A2, THRB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	15	EGFR, FGFR2, FGFR3, KRAS, PDGFRA, CCND1, CD274, SLTM, FGFR1, NFE2L2 (+5 more)
B	Phased (≥1) drug, not yet approved	3	SLC1A1, NPFFR1, NEK10
C	Druggable family + PDB, no drug	6	BTN3A2, BTN3A3, TNXB, ELAC2, WNK1, MASTL
D	Druggable family + AlphaFold only, no drug	6	VARS1, OR2B2, OR14J1, IPPK, LRP11, CATSPER2
E	Difficult family or no structure, no drug	45	XCL2, SLC1A6, BRCA2, SPI1, SYT4, TAC1, HNF1B, TMEFF1, VSNL1, WWOX (+35 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WNK1	165	—
XCL2	0	—
SLC1A6	0	—
BRCA2	0	—
SPI1	0	—
BTN3A2	0	—
BTN3A3	0	—
SYT4	0	—
TAC1	0	—
HNF1B	0	—
TMEFF1	0	—
TNXB	0	—
VARS1	7	—
VSNL1	0	—
WWOX	0	—
REXO4	0	—
XRCC4	1	—
ZNF165	0	—
TRIM26	0	—
ZNF184	0	—
ZSCAN9	0	—
ZNF204P	0	—
ZSCAN12	0	—
IKZF2	26	—
POLR1H	0	—
VN1R10P	0	—
HIVEP3	0	—
SNTG2	0	—
ZNF311	0	—
SCAND3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 112.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	40
Not specified	25
PHASE1	18
PHASE3	10
PHASE1/PHASE2	10
PHASE2/PHASE3	5
PHASE4	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07567313	PHASE4	NOT_YET_RECRUITING	Stage IV Lung Squamous Cell Carcinoma Treated With or Without Bronchial Artery Chemoembolization After First-line Chemotherapy and Immunotherapy
NCT03725423	PHASE4	UNKNOWN	Apatinib for Advanced Lung Squmamous Carcinoma
NCT04132102	PHASE4	UNKNOWN	To Evaluate the Efficacy of Afatinib in Advanced Lung Squamous Cell Carcinoma With EGFR Sensitive Mutation
NCT05782764	PHASE4	UNKNOWN	A Study of Endostar Combined With Chemotherapy and Immunotherapy in Lung Squamous Cell Carcinom
NCT02785952	PHASE3	ACTIVE_NOT_RECRUITING	Lung-MAP: Nivolumab With or Without Ipilimumab as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01082549	PHASE3	COMPLETED	Trial of Gemcitabine/Carboplatin With or Without Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects With Previously Untreated Stage IV Squamous Non-Small-Cell Lung Cancer (NSCLC)
NCT01947062	PHASE3	UNKNOWN	Metronomic Cyclophosphamide in Combination With Standard Chemotherapy for Squamous Cell Lung Carcinoma
NCT02766335	PHASE2/PHASE3	COMPLETED	Lung-MAP: Durvalumab as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers
NCT02785939	PHASE2/PHASE3	COMPLETED	Lung-MAP: Palbociclib as Second-Line Therapy in Treating Cell Cycle Gene Alteration Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer
NCT02926638	PHASE2/PHASE3	TERMINATED	Lung-MAP: Rilotumumab and Erlotinib Hydrochloride or Erlotinib Hydrochloride Alone as Second-Line Therapy in Treating Patients With Recurrent Stage IV Squamous Cell Lung Cancer and Positive Biomarker Matches
NCT02965378	PHASE2/PHASE3	COMPLETED	Lung-MAP: AZD4547 as Second-Line Therapy in Treating FGFR Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer
NCT03346304	PHASE2/PHASE3	WITHDRAWN	Photodynamic Therapy for the Prevention of Lung Cancer
NCT03866993	PHASE3	COMPLETED	A Study of Anti-PD-1 AK105 in Patients With Metastatic Squamous Non-small Cell Lung Cancer
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT01386385	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Veliparib With or Without Radiation Therapy, Carboplatin, and Paclitaxel in Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT04802876	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients with PD1-high MRNA Expressing Tumors
NCT05120271	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	BOXR1030 T Cells in Subjects With Advanced GPC3-Positive Solid Tumors
NCT05607108	PHASE2	RECRUITING	A Study of ZEN003694 in People With Squamous Cell Lung Cancer
NCT06121505	PHASE2	RECRUITING	Phase II Trial: Low-Dose Radiation + SBRT + Sintilimab + Chemotherapy vs. Sintilimab + Chemotherapy in Locally Advanced or Metastatic Squamous Cell Lung Cancer
NCT07009925	PHASE2	NOT_YET_RECRUITING	Phase II Study of Platinum (Cisplatin/Carboplatin)and Polymeric Micelles Paclitaxel(Pm-Pac) With Ivonescimab in First Line Metastatic Squamous NSCLC.
NCT07109726	PHASE1/PHASE2	RECRUITING	A Phase 1/2 Trial of TER-2013 in Patients With Solid Tumors Harboring AKT/PI3K/PTEN Pathway Alterations
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00368992	PHASE2	COMPLETED	S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
NCT00387374	PHASE2	COMPLETED	Radiation Therapy, Bevacizumab, Paclitaxel, and Carboplatin in Treating Patients With Unresectable Stage IIIB or Stage IV Non-Small Cell Lung Cancer at High Risk for Hemoptysis Caused by Bevacizumab
NCT01294306	PHASE2	COMPLETED	MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy
NCT01491633	PHASE2	TERMINATED	Dasatinib in Advanced Squamous Cell Lung Cancer
NCT01557959	PHASE2	COMPLETED	Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
NCT01660399	PHASE2	UNKNOWN	Clinical Trial of Boanmycin Hydrochloride With Docetaxel for Patients With Lung Squamous Cell Cancer as Chemotherapy
NCT01737502	PHASE1/PHASE2	COMPLETED	Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer
NCT01795768	PHASE2	UNKNOWN	Proof-of-Concept Study of AZD4547 in Patients With FGFR1 or FGFR2 Amplified Tumours
NCT01807546	PHASE2	COMPLETED	Oral Rigosertib for Squamous Cell Carcinoma
NCT01824901	PHASE1/PHASE2	COMPLETED	Docetaxel With or Without FGFR Inhibitor AZD4547 in Treating Patients With Recurrent Non-Small Cell Lung Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DOCETAXEL ANHYDROUS	4	3
GEFITINIB	4	3
CARBOPLATIN	4	2
ERLOTINIB HYDROCHLORIDE	4	2
PACLITAXEL	4	2
AFATINIB	4	1
AURANOFIN	4	1
CETUXIMAB	4	1
DURVALUMAB	4	1
ERDAFITINIB	4	1
ETOPOSIDE	4	1
GEMCITABINE	4	1
IPILIMUMAB	4	1
NINTEDANIB	4	1
NIVOLUMAB	4	1
PALBOCICLIB	4	1
PEGFILGRASTIM	4	1
PIRFENIDONE	4	1
RAMUCIRUMAB	4	1
SELINEXOR	4	1
SELUMETINIB	4	1
TREMELIMUMAB	4	1
TREOSULFAN	4	1
VALACYCLOVIR	4	1
VINORELBINE TARTRATE	4	1
ICOTINIB	3	2
IVONESCIMAB	3	2
RIGOSERTIB	3	2
RILOTUMUMAB	3	2
RIVOCERANIB	3	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 13 predictive associations from 14 curated evidence items; also 5 oncogenic, 4 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
NFE2L2 Mutation	Sapanisertib	Sensitivity/Response	CIViC B	EID7425 +1
CCND1 Amplification	Palbociclib	Sensitivity/Response	CIViC B	EID7405
CCND2 Amplification	Palbociclib	Sensitivity/Response	CIViC B	EID7406
CCND3 Amplification	Palbociclib	Sensitivity/Response	CIViC B	EID7407
FGFR1 Amplification	Infigratinib	Sensitivity/Response	CIViC B	EID1908
TMB Low on-treatment bTMB	Camrelizumab + Carboplatin/Paclitaxel Regimen	Sensitivity/Response	CIViC B	EID12919
EGFR T790M	Osimertinib	Sensitivity/Response	CIViC C	EID12066
MET Amplification	Crizotinib	Sensitivity/Response	CIViC C	EID890
MET D1010N	Crizotinib	Sensitivity/Response	CIViC C	EID4781
FGFR1 Amplification	PD173074	Sensitivity/Response	CIViC D	EID680
KMT2D Loss	SHP2 Inhibitor + Afatinib	Sensitivity/Response	CIViC D	EID12776
PDGFRA Amplification	Imatinib + Sunitinib	Sensitivity/Response	CIViC D	EID7989
KRAS G12S	Dasatinib	Resistance	CIViC D	EID4020