Small cell lung carcinoma

Summary

Small cell lung carcinoma (MONDO:0008433) is a cancer with 75 cohort genes (56 GWAS associations across 4 studies; 15 CIViC-evidence somatic drivers; 32 ClinVar predisposition records) and 762 clinical trials. The dominant Reactome pathway is Endosomal/Vacuolar pathway (3 cohort genes). Molecularly, DLL3 Expression confers sensitivity to Rovalpituzumab Tesirine in Lung Small Cell Carcinoma (CIViC Level B); 9 further subtype–drug associations are mapped below. Top therapeutic interventions include cisplatin, topotecan, and irinotecan.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 75
• GWAS associations: 56
• ClinVar variants: 32
• Clinical trials: 762
• Precision-medicine evidence (CIViC): 10 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	12	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	small cell lung carcinoma
Mondo ID	MONDO:0008433
EFO	EFO:0000702
MeSH	D055752
OMIM	182280
Orphanet	70573
DOID	DOID:5409, DOID:5411
ICD-11	1800431439
NCIT	C4917
SNOMED CT	254632001
UMLS	C0149925
MedGen	57450
GARD	0009344
Anatomy (UBERON)	UBERON:0002048
Is cancer (heuristic)	yes

Also known as: lung oat cell carcinoma · lung small cell carcinoma · lung small cell neuroendocrine carcinoma · oat cell carcinoma · oat cell carcinoma (morphologic abnormality) · oat cell carcinoma of lung · oat cell carcinoma of the lung · oat cell lung carcinoma · poorly differentiated endocrine neoplasm · SCLC · SCLC1 · small cell cancer of the lung, somatic · small cell carcinoma of lung · small cell carcinoma of the lung · Small cell lung cancer · small cell lung cancer · small cell neuroendocrine carcinoma of lung · small cell neuroendocrine carcinoma of the lung · small-cell cancer of lung

Data availability: 32 ClinVar variants · 56 GWAS associations (4 studies) · 556 cell lines · 27 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 › cancer › carcinoma › neuroendocrine carcinoma › small cell carcinoma › small cell lung carcinoma

Related subtypes (17): extrahepatic bile duct small cell adenocarcinoma, ovarian small cell carcinoma, colon small cell neuroendocrine carcinoma, urinary bladder small cell neuroendocrine carcinoma, esophageal small cell neuroendocrine carcinoma, ampulla of vater small cell neuroendocrine carcinoma, Bartholin gland small cell carcinoma, thymus small cell carcinoma, cervical small cell carcinoma, endometrial small cell carcinoma, gallbladder small cell neuroendocrine carcinoma, gastric small cell neuroendocrine carcinoma, laryngeal small cell carcinoma, pancreatic small cell neuroendocrine carcinoma, prostate small cell carcinoma, salivary gland small cell carcinoma, ureter small cell carcinoma

Subtypes (2): occult small cell lung carcinoma, combined small cell lung carcinoma

Genetics & variants

GWAS landscape

56 GWAS associations across 4 studies. Top hits map to 36 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs16969968	1e-23	CHRNA5	?	0.26
rs55853698	5e-21	CHRNA5	G	1.33
rs141174940	5e-10	VPS13B	C	8.24
rs3813565	1e-09	GOLGA6GP, CHRNB4	T	1.21
rs141178913	1e-09	IL17RC	G	2.43
rs191133092	7e-09	LINC01556 - KRT18P1	T	1.8
rs11571833	3e-08	BRCA2	T	2.19
rs116427960	5e-08	LINC02571 - HLA-B	T	1.25
rs716274	9e-08	DYNC2H1 - PDGFDDN	G	1.83
rs114033761	1e-07	RNU6-1133P - C6orf15	C	1.27
rs12981718	2e-07	VSTM1 - TARM1	A	1.36
rs181801863	2e-07	COX6C - RGS22	A	6.66
rs74501188	3e-07	ADGRV1	G	1.2
rs10118776	4e-07	IL33	G	1.34
rs9308062	5e-07	TMA16	T	1.17
rs117729306	7e-07	STK33	C	2.31
rs17185553	9e-07	ADAMTSL1	C	1.29
rs141670911	1e-06	HMGN4 - ABT1	A	1.29
rs140013431	1e-06	BMP6	C	1.66
rs141877527	1e-06	NRP1 - LINC02628	G	1.94
rs3134425	1e-06	CRTAM	C	1.16
rs12200782	1e-06	BTN3A1	C	1.28
rs8049634	1e-06	ADAD2	G	1.18
rs112037939	2e-06	HLA-DRB1 - HLA-DQA1	T	1.18
rs116877011	2e-06	SCIN	T	1.67
rs6463739	2e-06	UMAD1	G	1.16
rs138600791	2e-06	EPHB1 - SDHBP1	C	1.81
rs1703426	2e-06	FSTL4 - WSPAR	C	1.2
rs847245	2e-06	RGS6	G	1.51
rs140394255	2e-06	UBE2G1 - SPNS3	A	1.31

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004746	McKay JD	2017	2,664	21,444	Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.
GCST90134664	Byun J	2022	2,267	23,173	Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.
GCST000896	Wu C	2010	245	0	Genome-wide interrogation identifies YAP1 variants associated with survival of small-cell lung cancer patients.
GCST90624810	Betti MJ	2025	157	3,590	Genetic analysis in African ancestry populations reveals genetic contributors to lung cancer susceptibility.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	4
Tier 3: regulatory	1
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	32
low_freq (0.01-0.05)	13
rare (<0.01)	1
unknown	4

Functional consequences

Consequence	Count
intron_variant	26
intergenic_variant	16
missense_variant	2
3_prime_UTR_variant	2
5_prime_UTR_variant	1
splice_region_variant	1
stop_gained	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs16969968	15	78590583	G>A	0.05	missense_variant	CHRNA5	1e-23	Tier 1: coding
rs55853698	15	78565597	T>G	0.36	5_prime_UTR_variant	CHRNA5	5e-21	Tier 2: splice/UTR
rs141174940	8	99869228	T>C		intron_variant	VPS13B	5e-10	Tier 4: intronic/intergenic
rs3813565	15	78727268	G>A,T	0.401	splice_region_variant	GOLGA6GP, CHRNB4	1e-09	Tier 2: splice/UTR
rs141178913	3	9928389	C>G,T		missense_variant	IL17RC	1e-09	Tier 1: coding
rs191133092	6	28965208	A>T		intergenic_variant	LINC01556 - KRT18P1	7e-09	Tier 4: intronic/intergenic
rs11571833	13	32398489	A>T	0.01	stop_gained	BRCA2	3e-08	Tier 1: coding
rs116427960	6	31351449		0.156	intron_variant	LINC02571 - HLA-B	5e-08	Tier 4: intronic/intergenic
rs716274	11	103547430	A>G	0.05	intergenic_variant	DYNC2H1 - PDGFDDN	9e-08	Tier 4: intronic/intergenic
rs114033761	6	31093784		0.12	intergenic_variant	RNU6-1133P - C6orf15	1e-07	Tier 4: intronic/intergenic
rs12981718	19	54064604	G>A,T	0.072	intergenic_variant	VSTM1 - TARM1	2e-07	Tier 4: intronic/intergenic
rs181801863	8	99943454	G>A		intergenic_variant	COX6C - RGS22	2e-07	Tier 4: intronic/intergenic
rs74501188	5	90931162	G>A	0.224	intron_variant	ADGRV1	3e-07	Tier 4: intronic/intergenic
rs10118776	9	6227418	G>A,C,T	0.063	intron_variant	IL33	4e-07	Tier 4: intronic/intergenic
rs9308062	4	163517048	T>A,C	0.417	intron_variant	TMA16	5e-07	Tier 4: intronic/intergenic
rs117729306	11	8465623	T>C	0.011	intron_variant	STK33	7e-07	Tier 4: intronic/intergenic
rs17185553	9	17934122	G>C	0.081	intergenic_variant	ADAMTSL1	9e-07	Tier 4: intronic/intergenic
rs141670911	6	26581030	A>T	0.095	intergenic_variant	HMGN4 - ABT1	1e-06	Tier 4: intronic/intergenic
rs140013431	6	7770278	T>C	0.021	intron_variant	BMP6	1e-06	Tier 4: intronic/intergenic
rs141877527	10	33497992	A>C,G	0.013	intergenic_variant	NRP1 - LINC02628	1e-06	Tier 4: intronic/intergenic
rs3134425	11	122838470	T>C,G	0.381	intron_variant	CRTAM	1e-06	Tier 4: intronic/intergenic
rs12200782	6	26402808	C>G	0.097	intron_variant	BTN3A1	1e-06	Tier 4: intronic/intergenic
rs8049634	16	84192073	A>G	0.248	intron_variant	ADAD2	1e-06	Tier 4: intronic/intergenic
rs112037939	6	32623699		0.251	regulatory_region_variant	HLA-DRB1 - HLA-DQA1	2e-06	Tier 3: regulatory
rs116877011	7	12613434	C>T	0.02	intron_variant	SCIN	2e-06	Tier 4: intronic/intergenic
rs6463739	7	7867093	G>C,T	0.403	intron_variant	UMAD1	2e-06	Tier 4: intronic/intergenic
rs138600791	3	135461153	G>C	0.012	intergenic_variant	EPHB1 - SDHBP1	2e-06	Tier 4: intronic/intergenic
rs1703426	5	133849844	C>T	0.175	intergenic_variant	FSTL4 - WSPAR	2e-06	Tier 4: intronic/intergenic
rs847245	14	72249978	G>A,C,T	0.041	intron_variant	RGS6	2e-06	Tier 4: intronic/intergenic
rs140394255	17	4424688	G>A,C	0.075	intergenic_variant	UBE2G1 - SPNS3	2e-06	Tier 4: intronic/intergenic

ClinVar germline variants

32 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 10 conflicting classifications of pathogenicity, 9 pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
487484	t(2;2)(p23;p21)(hg19 chr2:g.42552694::ochr2:g.29446394)	ALK	Pathogenic	no assertion criteria provided
126820	NM_000321.3(RB1):c.763C>T (p.Arg255Ter)	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts
126832	NM_000321.3(RB1):c.1215+1G>A	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts
13071	NM_000321.3(RB1):c.1333C>T (p.Arg445Ter)	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts
13073	NM_000321.3(RB1):c.2359C>T (p.Arg787Ter)	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts
13078	NM_000321.3(RB1):c.2242G>T (p.Glu748Ter)	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts
13087	NM_000321.3(RB1):c.1981C>T (p.Arg661Trp)	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts
13093	NM_000321.3(RB1):c.607+1G>T	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts
3892259	NM_000321.3(RB1):c.460A>T (p.Lys154Ter)	RB1	Pathogenic	criteria provided, single submitter
458119	NM_000321.3(RB1):c.1174G>A (p.Ala392Thr)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
458158	NM_000321.3(RB1):c.269G>T (p.Gly90Val)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
458185	NM_000321.3(RB1):c.850A>G (p.Asn284Asp)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
458187	NM_000321.3(RB1):c.905C>A (p.Ser302Tyr)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
575378	NM_000321.3(RB1):c.752G>A (p.Arg251Gln)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
575576	NM_000321.3(RB1):c.536G>T (p.Ser179Ile)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
656058	NM_000321.3(RB1):c.897T>A (p.Phe299Leu)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
664139	NM_000321.3(RB1):c.339G>A (p.Met113Ile)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
818687	NM_000321.3(RB1):c.1240A>C (p.Ser414Arg)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
995890	NM_000321.3(RB1):c.1206C>T (p.Ser402=)	RB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001246	NM_000321.3(RB1):c.45_53dup (p.Ala16_Ala18dup)	RB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1038511	NM_000321.3(RB1):c.644C>T (p.Ser215Leu)	RB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2145424	NM_000321.3(RB1):c.2678G>T (p.Gly893Val)	RB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2960455	NM_000321.3(RB1):c.2017C>T (p.His673Tyr)	RB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3576262	NM_000321.3(RB1):c.1264A>G (p.Ile422Val)	RB1	Uncertain significance	criteria provided, single submitter
3576264	NM_000321.3(RB1):c.1285A>C (p.Lys429Gln)	RB1	Uncertain significance	criteria provided, single submitter
3576265	NM_000321.3(RB1):c.2482A>G (p.Arg828Gly)	RB1	Uncertain significance	criteria provided, single submitter
458162	NM_000321.3(RB1):c.276T>G (p.Ile92Met)	RB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
664716	NM_000321.3(RB1):c.1376C>T (p.Ser459Phe)	RB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
854366	NM_000321.3(RB1):c.352A>T (p.Thr118Ser)	RB1	Uncertain significance	criteria provided, multiple submitters, no conflicts
41684	NM_000321.3(RB1):c.411A>T (p.Glu137Asp)	RB1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 70 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

Gene	HGNC	Evidence routes
BRCA2	BRCA2	GWAS, Orphanet
HLA-B	HLA-B	GWAS, Orphanet
HLA-DRB1	HLA-DRB1	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RB1	LoF	ACC,BLADDER,BLCA,BRCA,CESC,ESCA,GB,GBM,GIST,HCC,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MEL,MT,NSCLC,OS,OVT,PANCREAS,PCM,PRAD,PROSTATE,RBL,SCLC,SKCM,SOFT_TISSUE,STAD,STOMACH,UCEC,UCS	CIViC #4795
CHEK1			CIViC #981
SLFN11			CIViC #16872
RICTOR			CIViC #20480
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
MYC	Act	AML,BL,MLYM,NHL	CIViC #3737
BMP6	Act	PRAD
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
ALDH1A2			CIViC #7024
IL33			CIViC #16802
ALK	Act	BRCA,HCC,NBL,NSCLC,PROSTATE,SCLC	CIViC #1
HLA-B	LoF	CESC,DLBCLNOS,ESCA,HNSC,MLYM	CIViC #2607
HLA-C	LoF	DLBCLNOS	CIViC #2608
HLA-DQA1	Act	PLMESO

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RB1	Orphanet:1587	Monosomy 13q14 syndrome
RB1	Orphanet:357027	Hereditary retinoblastoma
RB1	Orphanet:357034	Non-hereditary retinoblastoma
RB1	Orphanet:668	Osteosarcoma
RB1	Orphanet:70573	Small cell lung cancer
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
MYC	Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
MYC	Orphanet:543	Burkitt lymphoma
MYC	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
BMP6	Orphanet:465508	Symptomatic form of HFE-related hemochromatosis
DST	Orphanet:314381	Hereditary sensory and autonomic neuropathy type 6
DST	Orphanet:412181	Epidermolysis bullosa simplex due to BP230 deficiency
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
ADAMTSL1	Orphanet:521445	Microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome
ADGRV1	Orphanet:231178	Usher syndrome type 2
ADGRV1	Orphanet:36387	Genetic epilepsy with febrile seizure plus
DYNC2H1	Orphanet:474	Jeune syndrome
DYNC2H1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
DYNC2H1	Orphanet:93270	Short rib-polydactyly syndrome, Saldino-Noonan type
DYNC2H1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
PHC1	Orphanet:2512	Autosomal recessive primary microcephaly
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus
ALK	Orphanet:635	Neuroblastoma
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome

Cohort genes → proteins

75 cohort genes, 61 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	67
civic_only	6
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	clinvar,civic_evidence
CHEK1	HGNC:1925	ENSG00000149554	O14757	Serine/threonine-protein kinase Chk1	civic_evidence
SLFN11	HGNC:26633	ENSG00000172716	Q7Z7L1	Schlafen family member 11	civic_evidence
RICTOR	HGNC:28611	ENSG00000164327	Q6R327	Rapamycin-insensitive companion of mTOR	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
ERBB2	HGNC:3430	ENSG00000141736	P04626	Receptor tyrosine-protein kinase erbB-2	civic_evidence
MYC	HGNC:7553	ENSG00000136997	P01106	Myc proto-oncogene protein	civic_evidence
RGS6	HGNC:10002	ENSG00000182732	P49758	Regulator of G-protein signaling 6	gwas
BMP6	HGNC:1073	ENSG00000153162	P22004	Bone morphogenetic protein 6	gwas
SH3GL2	HGNC:10831	ENSG00000107295	Q99962	Endophilin-A1	gwas
DST	HGNC:1090	ENSG00000151914	Q03001	Dystonin	gwas
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	gwas
BTN3A1	HGNC:1138	ENSG00000026950	O00481	Butyrophilin subfamily 3 member A1	gwas
UBE2G1	HGNC:12482	ENSG00000132388	P62253	Ubiquitin-conjugating enzyme E2 G1	gwas
BAG6	HGNC:13919	ENSG00000204463	P46379	Large proline-rich protein BAG6	gwas
C6orf15	HGNC:13927	ENSG00000204542	Q6UXA7	Uncharacterized protein C6orf15	gwas
ZNF322P1	HGNC:14003	ENSG00000188801		zinc finger protein 322 pseudogene 1	gwas
SGCZ	HGNC:14075	ENSG00000185053	Q96LD1	Zeta-sarcoglycan	gwas
BBX	HGNC:14422	ENSG00000114439	Q8WY36	HMG box transcription factor BBX	gwas
STK33	HGNC:14568	ENSG00000130413	Q9BYT3	Serine/threonine-protein kinase 33	gwas
ADAMTSL1	HGNC:14632	ENSG00000178031	Q8N6G6	ADAMTS-like protein 1	gwas
ALDH1A2	HGNC:15472	ENSG00000128918	O94788	Retinal dehydrogenase 2	gwas
FAM167A-AS1	HGNC:15548	ENSG00000184608	Q96KT0	Uncharacterized protein FAM167A-AS1	gwas
SKAP2	HGNC:15687	ENSG00000005020	O75563	Src kinase-associated phosphoprotein 2	gwas
IL33	HGNC:16028	ENSG00000137033	O95760	Interleukin-33	gwas
COL21A1	HGNC:17025	ENSG00000124749	Q96P44	Collagen alpha-1(XXI) chain	gwas
ABT1	HGNC:17369	ENSG00000146109	Q9ULW3	Activator of basal transcription 1	gwas
ADGRV1	HGNC:17416	ENSG00000164199	Q8WXG9	Adhesion G-protein coupled receptor V1	gwas
SFTA2	HGNC:18386	ENSG00000196260	Q6UW10	Surfactant-associated protein 2	gwas
PIWIL4	HGNC:18444	ENSG00000134627	Q7Z3Z4	Piwi-like protein 4	gwas
GUSBP2	HGNC:18792	ENSG00000241549		GUSB pseudogene 2	gwas
FOXN3	HGNC:1928	ENSG00000053254	O00409	Forkhead box protein N3	gwas
CHRNA5	HGNC:1959	ENSG00000169684	P30532	Neuronal acetylcholine receptor subunit alpha-5	gwas
CHRNB4	HGNC:1964	ENSG00000117971	P30926	Neuronal acetylcholine receptor subunit beta-4	gwas
TMEM179	HGNC:20137	ENSG00000258986	Q6ZVK1	Transmembrane protein 179	gwas
HCG4	HGNC:21241	ENSG00000176998		HLA complex group 4	gwas
FSTL4	HGNC:21389	ENSG00000053108	Q6MZW2	Follistatin-related protein 4	gwas
IFITM4P	HGNC:21669	ENSG00000235821		interferon induced transmembrane protein 4 pseudogene	gwas
SCIN	HGNC:21695	ENSG00000006747	Q9Y6U3	Scinderin	gwas
A2ML1	HGNC:23336	ENSG00000166535	A8K2U0	Alpha-2-macroglobulin-like protein 1	gwas
CRTAM	HGNC:24313	ENSG00000109943	O95727	Cytotoxic and regulatory T-cell molecule	gwas
FCHO2	HGNC:25180	ENSG00000157107	Q0JRZ9	F-BAR domain only protein 2	gwas
TMA16	HGNC:25638	ENSG00000198498	Q96EY4	Translation machinery-associated protein 16	gwas
MARCHF1	HGNC:26077	ENSG00000145416	Q8TCQ1	E3 ubiquitin-protein ligase MARCHF1	gwas
LINC00615	HGNC:26343	ENSG00000196243	Q96LM1	Putative uncharacterized protein encoded by LINC00615	gwas
C8orf48	HGNC:26345	ENSG00000164743	Q96LL4	Uncharacterized protein C8orf48	gwas
HCG22	HGNC:27780	ENSG00000228789	E2RYF7	Protein PBMUCL2	gwas
ATP2B1-AS1	HGNC:27883	ENSG00000271614		ATP2B1 antisense RNA 1	gwas
SPNS3	HGNC:28433	ENSG00000182557	Q6ZMD2	Protein spinster homolog 3	gwas
VSTM1	HGNC:29455	ENSG00000189068	Q6UX27	V-set and transmembrane domain-containing protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.
CHEK1	Serine/threonine-protein kinase Chk1	Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA.
SLFN11	Schlafen family member 11	Inhibitor of DNA replication that promotes cell death in response to DNA damage.
RICTOR	Rapamycin-insensitive companion of mTOR	Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output.
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.
MYC	Myc proto-oncogene protein	Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5’-CAC[GA]TG-3'.
RGS6	Regulator of G-protein signaling 6	Regulates G protein-coupled receptor signaling cascades.
BMP6	Bone morphogenetic protein 6	Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation.
SH3GL2	Endophilin-A1	Implicated in synaptic vesicle endocytosis.
DST	Dystonin	Cytoskeletal linker protein.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
BTN3A1	Butyrophilin subfamily 3 member A1	Plays a role in T-cell activation and in the adaptive immune response.
UBE2G1	Ubiquitin-conjugating enzyme E2 G1	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
BAG6	Large proline-rich protein BAG6	ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins.
SGCZ	Zeta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
BBX	HMG box transcription factor BBX	Transcription factor that is necessary for cell cycle progression from G1 to S phase.
STK33	Serine/threonine-protein kinase 33	Serine/threonine protein kinase required for spermatid differentiation and male fertility.
ALDH1A2	Retinal dehydrogenase 2	Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
SKAP2	Src kinase-associated phosphoprotein 2	May be involved in B-cell and macrophage adhesion processes.
IL33	Interleukin-33	Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.
ABT1	Activator of basal transcription 1	Could be a novel TATA-binding protein (TBP) which can function as a basal transcription activator.
ADGRV1	Adhesion G-protein coupled receptor V1	G-protein coupled receptor which has an essential role in the development of hearing and vision.
SFTA2	Surfactant-associated protein 2	Putative surfactant protein.
PIWIL4	Piwi-like protein 4	Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity.
FOXN3	Forkhead box protein N3	Acts as a transcriptional repressor.
CHRNA5	Neuronal acetylcholine receptor subunit alpha-5	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…
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…
SCIN	Scinderin	Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane.
A2ML1	Alpha-2-macroglobulin-like protein 1	Is able to inhibit all four classes of proteinases by a unique ’trapping’ mechanism.
CRTAM	Cytotoxic and regulatory T-cell molecule	Mediates heterophilic cell-cell adhesion which regulates the activation, differentiation and tissue retention of various T-cell subsets.
FCHO2	F-BAR domain only protein 2	Functions in an early step of clathrin-mediated endocytosis.
TMA16	Translation machinery-associated protein 16	Involved in the biogenesis of the 60S ribosomal subunit in the nucleus.
MARCHF1	E3 ubiquitin-protein ligase MARCHF1	E3 ubiquitin-protein ligase that mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies.
SPNS3	Protein spinster homolog 3	Sphingolipid transporter.
VSTM1	V-set and transmembrane domain-containing protein 1	Behaves as a cytokine, promoting IL17A secretion by CD4+ T-cells, and differentiation and activation of IL17 producing helper T-cells (TH17).
DYNC2H1	Cytoplasmic dynein 2 heavy chain 1	May function as a motor for intraflagellar retrograde transport.
ADAD2	Adenosine deaminase domain-containing protein 2	Required for male fertility and normal male germ cell differentiation.
PHC1	Polyhomeotic-like protein 1	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
EPHB1	Ephrin type-B receptor 1	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
FUT4	Alpha-(1,3)-fucosyltransferase 4	Catalyzes alpha(1->3) linkage of fucosyl moiety transferred from GDP-beta-L-fucose to N-acetyl glucosamine (GlcNAc) within type 2 lactosamine (LacNAc, Gal-beta(1->4)GlcNAc) glycan attached to N- or O-linked glycoproteins.
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.
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
HLA-C	HLA class I histocompatibility antigen, C alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-E	HLA class I histocompatibility antigen, alpha chain E	Non-classical major histocompatibility class Ib molecule involved in immune self-nonself discrimination.
HOXA1	Homeobox protein Hox-A1	Sequence-specific transcription factor.
IER3	Radiation-inducible immediate-early gene IEX-1	May play a role in the ERK signaling pathway by inhibiting the dephosphorylation of ERK by phosphatase PP2A-PPP2R5C holoenzyme.
AQP7	Aquaporin-7	Aquaglyceroporins form homotetrameric transmembrane channels, with each monomer independently mediating glycerol and water transport across the plasma membrane along their osmotic gradient.

Protein-family classification

Druggable: 22 · Difficult: 10 · Unknown: 43 · Druggable fraction: 0.29

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
Antibody/Immunoglobulin	10	3.9×	0.002
Kinase	6	2.2×	0.240
Complement	1	3.6×	0.735
Transporter	1	1.0×	0.956
Other/Unknown	43	1.0×	0.956
Scaffold/PPI	4	0.9×	0.956
Transcription factor	6	0.7×	0.960
Enzyme (other)	3	0.5×	0.960
GPCR	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom
CHEK1	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SLFN11	Other/Unknown	no		Schlafen_AlbA_2_dom, SLFN_3-like_DNA/RNA_helicase, P-loop_NTPase
RICTOR	Other/Unknown	no		ARM-type_fold, Pianissimo_N, Pianissimo_fam
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
MYC	Transcription factor	no		Tscrpt_reg_Myc, Myc-LZ, bHLH_dom
RGS6	Other/Unknown	no		DEP_dom, G-protein_gamma-like_dom, RGS
BMP6	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
SH3GL2	Scaffold/PPI	no		SH3_domain, BAR_dom, AH/BAR_dom_sf
DST	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
BTN3A1	Antibody/Immunoglobulin	yes		B30.2/SPRY, Ig_sub, SPRY_dom
UBE2G1	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
BAG6	Other/Unknown	no		Ubiquitin-like_dom, Ubiquitin_CS, BAG6
C6orf15	Other/Unknown	no		C6orf15
ZNF322P1	Other/Unknown	no
SGCZ	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
BBX	Transcription factor	no		HMG_box_dom, TF_HMG_box_BBX_DUF2028, HMG_box_dom_sf
STK33	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ADAMTSL1	Antibody/Immunoglobulin	yes		TSP1_rpt, Ig_sub2, Ig_sub
ALDH1A2	Enzyme (other)	yes	1.2.1.36	Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
FAM167A-AS1	Other/Unknown	no
SKAP2	Scaffold/PPI	no		SH3_domain, PH_domain, PH-like_dom_sf
IL33	Other/Unknown	no		IL-33, IL33_C
COL21A1	Other/Unknown	no		VWF_A, Collagen, ConA-like_dom_sf
ABT1	Other/Unknown	no		Nucleotide-bd_a/b_plait_sf, ABT1/ESF2_RRM, RBD_domain_sf
ADGRV1	GPCR	yes		GPCR_2_secretin-like, Calx_beta, EPTP
SFTA2	Other/Unknown	no		SFTA2
PIWIL4	Other/Unknown	no		PAZ_dom, Piwi, RNaseH-like_sf
GUSBP2	Other/Unknown	no
FOXN3	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
CHRNA5	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
CHRNB4	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
TMEM179	Other/Unknown	no		TMEM179, TMEM179-179B
HCG4	Other/Unknown	no
FSTL4	Antibody/Immunoglobulin	yes		EF_hand_dom, Kazal_dom, Ig_sub2
IFITM4P	Other/Unknown	no
SCIN	Other/Unknown	no		Villin/Gelsolin, Gelsolin-like_dom, ADF-H/Gelsolin-like_dom_sf
A2ML1	Complement	yes		Macroglobln_a2, MG2, Terpenoid_cyclase/PrenylTrfase
CRTAM	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
FCHO2	Scaffold/PPI	no		FCH_dom, Muniscin_C, AH/BAR_dom_sf
TMA16	Other/Unknown	no		Tma16, Tma16_sf
MARCHF1	Transcription factor	no		Znf_RING, Znf_RING-CH, Znf_RING/FYVE/PHD
LINC00615	Other/Unknown	no
C8orf48	Other/Unknown	no		DUF4606
HCG22	Other/Unknown	no		EZH_Inhibitor
ATP2B1-AS1	Other/Unknown	no
SPNS3	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
VSTM1	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig-like_fold

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	1
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	16
primordial germ cell in gonad	10
secondary oocyte	10
granulocyte	8
calcaneal tendon	7
sural nerve	7
monocyte	6
lower esophagus mucosa	5
right uterine tube	5
sperm	5
right lung	5
blood	5
oocyte	4
leukocyte	4
testis	4
corpus callosum	3
endothelial cell	3
ventricular zone	3
spleen	3
right testis	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura
CHEK1	210	ubiquitous	marker	secondary oocyte, oocyte, primordial germ cell in gonad
SLFN11	215	ubiquitous	marker	monocyte, leukocyte, calcaneal tendon
RICTOR	263	ubiquitous	marker	kidney epithelium, corpus callosum, tibialis anterior
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ERBB2	276	ubiquitous	marker	lower esophagus mucosa, right uterine tube, sural nerve
MYC	256	ubiquitous	marker	upper leg skin, vena cava, left uterine tube
RGS6	185	broad	marker	cortical plate, sural nerve, middle temporal gyrus
BMP6	197	ubiquitous	marker	secondary oocyte, cartilage tissue, oocyte
SH3GL2	193	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell
DST	305	ubiquitous	marker	corpus callosum, calcaneal tendon, medial globus pallidus
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
BTN3A1	272	ubiquitous	marker	granulocyte, spleen, pancreatic ductal cell
UBE2G1	294	ubiquitous	marker	sperm, secondary oocyte, biceps brachii
BAG6	144	ubiquitous	marker	right testis, left testis, testis
C6orf15	31	tissue_specific	yes	skin of leg, zone of skin, skin of abdomen
ZNF322P1	32	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, corpus callosum, bone marrow cell
SGCZ	70	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, oocyte, secondary oocyte
BBX	292	ubiquitous	marker	corpus epididymis, cauda epididymis, caput epididymis
STK33	181	broad	marker	right uterine tube, adenohypophysis, bronchial epithelial cell
ADAMTSL1	182	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, sural nerve
ALDH1A2	226	broad	marker	germinal epithelium of ovary, decidua, sperm
FAM167A-AS1	101	tissue_specific	yes	right uterine tube, fallopian tube, body of pancreas
SKAP2	287	ubiquitous	marker	sperm, secondary oocyte, pericardium
IL33	239	broad	marker	calcaneal tendon, right coronary artery, olfactory segment of nasal mucosa
COL21A1	239	broad	marker	blood vessel layer, bronchial epithelial cell, sural nerve
ABT1	243	ubiquitous	marker	granulocyte, leukocyte, monocyte
ADGRV1	196	broad	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
SFTA2	121	tissue_specific	marker	right lung, upper lobe of left lung, lower esophagus mucosa
PIWIL4	211	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, bone marrow

Protein interactions among cohort

Intra-cohort edges: 14.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYC	20,608
EGFR	18,421
ERBB2	9,659
CHEK1	4,939
BRCA2	4,839
ALK	4,792
RB1	4,374
ALDH1A2	4,289
RICTOR	4,055
HLA-DRB1	3,448

Intra-cohort edges

A	B	Sources
A2ML1	DST	string_interaction
ABT1	BBX	intact
ABT1	HMGN4	string_interaction
BAG6	IER3	intact
C8orf48	SGCZ	string_interaction
CHRNA5	CHRNB4	intact
EGFR	ERBB2	intact, string_interaction
EGFR	SH3GL2	biogrid_interaction
EGFR	SKAP2	intact
FCHO2	SH3GL2	string_interaction
HLA-B	HLA-C	biogrid_interaction, intact
HLA-B	HLA-E	biogrid_interaction, intact
HLA-C	HLA-E	biogrid_interaction, intact
HLA-DQA1	SH3GL2	intact

Structural data

PDB: 36 · AlphaFold-only: 25 · No structure: 14

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EGFR	P00533	388
HLA-B	P01889	237
CHEK1	O14757	164
HLA-DRB1	P01911	108
ALK	Q9UM73	79
ERBB2	P04626	63
BTN3A1	O00481	44
HLA-E	P13747	34
HLA-DQA1	P01909	28
MYC	P01106	25
RB1	P06400	19
RICTOR	Q6R327	16
BRCA2	P51587	14
HLA-C	P10321	13
BAG6	P46379	10
TMA16	Q96EY4	9
SLFN11	Q7Z7L1	8
EPHB1	P54762	8
AQP7	O14520	8
ALDH1A2	O94788	7
FCHO2	Q0JRZ9	7
BMP6	P22004	5
IL33	O95760	5
A2ML1	A8K2U0	5
SH3GL2	Q99962	4
CHRNB4	P30926	4
DYNC2H1	Q8NCM8	4
SCIN	Q9Y6U3	3
DST	Q03001	2
UBE2G1	P62253	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMEM179	Q6ZVK1	88.99
PIWIL4	Q7Z3Z4	85.84
SPNS3	Q6ZMD2	85.21
CHRNA5	P30532	82.04
FSTL4	Q6MZW2	81.18
SGCZ	Q96LD1	80.59
ABT1	Q9ULW3	78.08
VSTM1	Q6UX27	77.00
ADAD2	Q8NCV1	76.35
FUT4	P22083	74.21
ADAMTSL1	Q8N6G6	71.26
MARCHF1	Q8TCQ1	70.17
HCG22	E2RYF7	69.41
COL21A1	Q96P44	68.41
SFTA2	Q6UW10	67.28
IER3	P46695	66.00
C8orf48	Q96LL4	65.98
HMGN4	O00479	65.41
UMAD1	C9J7I0	61.63
HOXA1	P49639	59.15
FAM167A-AS1	Q96KT0	52.95
BBX	Q8WY36	50.79
C6orf15	Q6UXA7	43.65
LINC00615	Q96LM1	34.77
ADGRV1	Q8WXG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 301. Enrichment computed across 80 evidence-associated genes (41 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 41 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Endosomal/Vacuolar pathway	3	76.0×	0.002	HLA-B, HLA-C, HLA-E
Interferon gamma signaling	5	15.3×	0.003	HLA-B, HLA-C, HLA-DQA1, HLA-DRB1, HLA-E
PLCG1 events in ERBB2 signaling	2	139.3×	0.006	EGFR, ERBB2
DAP12 interactions	3	34.8×	0.006	HLA-B, HLA-C, HLA-E
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	3	28.8×	0.009	HLA-B, HLA-C, HLA-E
Highly calcium permeable nicotinic acetylcholine receptors	2	61.9×	0.022	CHRNA5, CHRNB4
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors	2	50.6×	0.026	CHRNA5, CHRNB4
Presynaptic nicotinic acetylcholine receptors	2	46.4×	0.026	CHRNA5, CHRNB4
HDR through MMEJ (alt-NHEJ)	2	42.9×	0.026	BRCA2, RAD52
Acetylcholine binding and downstream events	2	39.8×	0.026	CHRNA5, CHRNB4
Postsynaptic nicotinic acetylcholine receptors	2	39.8×	0.026	CHRNA5, CHRNB4
ERBB2 Activates PTK6 Signaling	2	39.8×	0.026	EGFR, ERBB2
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	37.1×	0.026	EGFR, ERBB2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	4	9.4×	0.026	IL33, EGFR, ERBB2, IER3
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	4	8.5×	0.026	CRTAM, HLA-B, HLA-C, HLA-E
ERBB2 Regulates Cell Motility	2	34.8×	0.028	EGFR, ERBB2
PI3K events in ERBB2 signaling	2	32.8×	0.028	EGFR, ERBB2
Signaling by ERBB2 ECD mutants	2	32.8×	0.028	EGFR, ERBB2
GRB2 events in ERBB2 signaling	2	30.9×	0.028	EGFR, ERBB2
Translocation of ZAP-70 to Immunological synapse	2	30.9×	0.028	HLA-DQA1, HLA-DRB1
Defective translocation of RB1 mutants to the nucleus	1	278.5×	0.028	RB1
Drug resistance of ALK mutants	1	278.5×	0.028	ALK
ASP-3026-resistant ALK mutants	1	278.5×	0.028	ALK
NVP-TAE684-resistant ALK mutants	1	278.5×	0.028	ALK
alectinib-resistant ALK mutants	1	278.5×	0.028	ALK
brigatinib-resistant ALK mutants	1	278.5×	0.028	ALK
ceritinib-resistant ALK mutants	1	278.5×	0.028	ALK
crizotinib-resistant ALK mutants	1	278.5×	0.028	ALK
lorlatinib-resistant ALK mutants	1	278.5×	0.028	ALK
Signaling by ALK	2	27.9×	0.028	ALK, MYC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 58 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	3	67.0×	0.003	HLA-B, HLA-C, HLA-E
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	3	67.0×	0.003	HLA-B, HLA-C, HLA-E
positive regulation of T cell mediated cytotoxicity	4	35.2×	0.003	HLA-B, HLA-C, HLA-DRB1, HLA-E
adaptive immune response	6	8.7×	0.011	BTN3A1, CRTAM, HLA-B, HLA-C, HLA-DQA1, HLA-E
positive regulation of epithelial cell proliferation	4	16.8×	0.013	BMP6, EGFR, ERBB2, MYC
positive regulation of natural killer cell mediated cytotoxicity	3	29.1×	0.017	CRTAM, HLA-C, HLA-E
protection from natural killer cell mediated cytotoxicity	2	96.8×	0.018	HLA-B, HLA-E
immune response	7	5.7×	0.019	BMP6, MARCHF1, HLA-B, HLA-C, HLA-DQA1, HLA-DRB1, HLA-E
mitotic G2 DNA damage checkpoint signaling	3	22.9×	0.024	CHEK1, FOXN3, IER3
behavioral response to nicotine	2	64.6×	0.027	CHRNA5, CHRNB4
lymphocyte migration into lymphoid organs	2	64.6×	0.027	CRTAM, NEDD9
ERBB2-EGFR signaling pathway	2	58.1×	0.031	EGFR, ERBB2
detection of bacterium	2	48.4×	0.039	HLA-B, HLA-DRB1
kidney development	4	9.7×	0.039	BMP6, BAG6, ALDH1A2, DYNC2H1
positive regulation of antibody-dependent cellular cytotoxicity	1	290.6×	0.050	HLA-E
regulation of natural killer cell mediated immunity	1	290.6×	0.050	HLA-E
determination of bilateral symmetry	1	290.6×	0.050	ALDH1A2
positive regulation of cellular defense response	1	290.6×	0.050	IL33
negative regulation of brain-derived neurotrophic factor receptor signaling pathway	1	290.6×	0.050	FSTL4
regulation of interleukin-4 production	1	290.6×	0.050	HLA-DRB1
double-strand break repair via single-strand annealing	1	290.6×	0.050	RAD52
regulation of endopeptidase activity	1	290.6×	0.050	A2ML1
semicircular canal formation	1	290.6×	0.050	HOXA1
positive regulation of metanephric cap mesenchymal cell proliferation	1	290.6×	0.050	MYC
negative regulation of macrophage proliferation	1	290.6×	0.050	IL33
positive regulation of lymphocyte chemotaxis	1	290.6×	0.050	NEDD9
basal dendrite development	1	290.6×	0.050	NRP1
positive regulation of acinar cell proliferation	1	290.6×	0.050	MYC
negative regulation of cardiocyte differentiation	1	290.6×	0.050	EGFR
acinar cell proliferation	1	290.6×	0.050	MYC

Therapeutics

Drugs indicated for this disease

5 approved, 37 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Atezolizumab	Approved (phase 4)
Durvalumab	Approved (phase 4)
Etoposide	Approved (phase 4)
Lurbinectedin	Approved (phase 4)
Tarlatamab	Approved (phase 4)
Adebrelimab	Phase 3 (in late-stage trials)
Amrubicin	Phase 3 (in late-stage trials)
Belotecan	Phase 3 (in late-stage trials)
Benmelstobart	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Catequentinib	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Darbepoetin Alfa	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Ibcasertib	Phase 3 (in late-stage trials)
Ifinatamab Deruxtecan	Phase 3 (in late-stage trials)
Ifosfamide	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Mitumomab	Phase 3 (in late-stage trials)
Nibrozetone	Phase 3 (in late-stage trials)
Niraparib	Phase 3 (in late-stage trials)
Olaparib	Phase 3 (in late-stage trials)
Palifosfamide	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Pemetrexed	Phase 3 (in late-stage trials)
Picoplatin	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Rovalpituzumab Tesirine	Phase 3 (in late-stage trials)
Serplulimab	Phase 3 (in late-stage trials)
Socazolimab	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Tiragolumab	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)
Topotecan	Phase 3 (in late-stage trials)
Toripalimab	Phase 3 (in late-stage trials)
Tremelimumab	Phase 3 (in late-stage trials)
Trilaciclib	Phase 3 (in late-stage trials)
Vibostolimab	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Afatinib, Aflibercept, Aldoxorubicin, Alisertib, Arsenic Trioxide, Avelumab, Becatecarin, Beclomethasone Dipropionate, Bemiparin, Bendamustine, Bevacizumab, CM-082, Cabazitaxel, Cediranib, Ceralasertib, Dasatinib Anhydrous, Dextrin, Dinutuximab, Dostarlimab, Endostatin, N-Terminal-Mggshhhhh, Enoxaparin Sodium, Enzastaurin, Epacadostat, Epirubicin, Everolimus, Famitinib, Figitumumab, Filgrastim, Ganetespib, Gefitinib, Gemcitabine, Gimeracil, Glufosfamide, Guadecitabine, Hydroxychloroquine, Ivonescimab, Lamivudine, Lenvatinib, Linsitinib, Lobaplatin, Metformin, Monalizumab, Navtemadlin, Nintedanib, Nivolumab, Oblimersen Sodium, Ociperlimab, Oteracil, Oxaliplatin, Paclitaxel, Pamiparib, Pasireotide, Pazopanib, Pegargiminase, Pegfilgrastim, Penpulimab, Platinum, Plinabulin, Ponatinib, Reminertant, Romidepsin, Selinexor, Simvastatin, Sintilimab, Sitravatinib, Sorafenib, Sugemalimab, Sunitinib, Surufatinib, Talazoparib, Tegafur, Temozolomide, Temsirolimus, Thymalfasin, Tirapazamine, Tivantinib, Tretinoin, Valproic Acid, Vandetanib, Veliparib, Vindesine, Vinflunine, Vismodegib, Vosaroxin.

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 10 · Phased (≥1): 13 · Undrugged: 62

Druggability breadth: 25 of 80 evidence-associated genes (31%) 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
CHEK1	FEDRATINIB
EGFR	LEVODOPA
ERBB2	CLOTRIMAZOLE
BTN3A1	ZOLEDRONIC ACID
STK33	FEDRATINIB
CHRNA5	VARENICLINE
CHRNB4	VARENICLINE
EPHB1	FEDRATINIB
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EGFR	175	4
ERBB2	83	4
ALK	61	4
CHEK1	36	4
EPHB1	28	4
STK33	22	4
CHRNB4	20	4
RICTOR	5	2
MYC	3	3
BTN3A1	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	ALK, CHEK1, EGFR, EPHB1, STK33
NERATINIB	4	CHEK1, EGFR, ERBB2, STK33
PALBOCICLIB	4	ALK, CHEK1
BOSUTINIB	4	ALK, CHEK1, EGFR, EPHB1, ERBB2, STK33
BRIGATINIB	4	ALK, CHEK1, EGFR, ERBB2
NINTEDANIB	4	ALK, CHEK1, EPHB1, STK33
SUNITINIB	4	ALK, CHEK1, EGFR, EPHB1, STK33
MIDOSTAURIN	4	ALK, CHEK1, EGFR, STK33
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR, ERBB2
ERLOTINIB HYDROCHLORIDE	4	EGFR, ERBB2
CISPLATIN	4	EGFR
PONATINIB	4	EGFR, ERBB2
AFATINIB	4	EGFR, ERBB2
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR, ERBB2
VEMURAFENIB	4	EGFR
AXITINIB	4	EGFR
SORAFENIB	4	EGFR, EPHB1, ERBB2, STK33
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	ALK, EGFR
IBRUTINIB	4	EGFR, ERBB2
AFATINIB DIMALEATE	4	EGFR, ERBB2
CABOZANTINIB	4	EGFR, ERBB2
DACOMITINIB	4	EGFR, ERBB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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
ALK	1,815	Binding:1801, Functional:13, ADMET:1
ERBB2	1,221	Binding:1136, Functional:79, ADMET:6
CHEK1	1,086	Binding:1039, Functional:44, ADMET:3
CHRNB4	407	Binding:309, Functional:96, ADMET:2
EPHB1	273	Binding:273
STK33	214	Binding:213, Functional:1
MYC	202	Binding:202
RICTOR	99	Binding:99
BTN3A1	75	Binding:75
RB1	59	Binding:59
ALDH1A2	32	Binding:32
CHRNA5	21	Binding:16, Functional:4, ADMET:1
HLA-DRB1	17	Binding:17
SLFN11	6	Binding:6
FUT4	6	Binding:6
HLA-DQA1	2	Binding:2
BMP6	1	Binding:1
BAG6	1	Binding:1
IL33	1	Binding:1
HLA-B	1	Binding:1
HLA-C	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHEK1	2.7.11.1	non-specific serine/threonine protein kinase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ERBB2	2.7.10.1	receptor protein-tyrosine kinase
UBE2G1	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
ALDH1A2	1.2.1.36	retinal dehydrogenase
EPHB1	2.7.10.1	receptor protein-tyrosine kinase
FUT4	2.4.1.152	4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase
ALK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CHEK1	1,086
EGFR	6,531
ERBB2	1,221
MYC	202
STK33	214
CHRNB4	407
EPHB1	273
ALK	1,815

Pharmacogenomics

Cohort genes with a PharmGKB record: 64; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

Drug repurposing candidates

29 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)
FEDRATINIB	4	ALK, CHEK1, EGFR, EPHB1, STK33
NERATINIB	4	CHEK1, EGFR, ERBB2, STK33
PALBOCICLIB	4	ALK, CHEK1
BOSUTINIB	4	ALK, CHEK1, EGFR, EPHB1, ERBB2, STK33
BRIGATINIB	4	ALK, CHEK1, EGFR, ERBB2
NINTEDANIB	4	ALK, CHEK1, EPHB1, STK33
SUNITINIB	4	ALK, CHEK1, EGFR, EPHB1, STK33
MIDOSTAURIN	4	ALK, CHEK1, EGFR, STK33
LEVODOPA	4	EGFR
CLOTRIMAZOLE	4	EGFR, ERBB2
ERLOTINIB HYDROCHLORIDE	4	EGFR, ERBB2
PONATINIB	4	EGFR, ERBB2
AFATINIB	4	EGFR, ERBB2
CHROMIC CHLORIDE	4	EGFR
BACITRACIN	4	EGFR
ZINC CHLORIDE	4	EGFR
LAPATINIB DITOSYLATE	4	EGFR, ERBB2
VEMURAFENIB	4	EGFR
AXITINIB	4	EGFR
SORAFENIB	4	EGFR, EPHB1, ERBB2, STK33
DASATINIB ANHYDROUS	4	EGFR
NICLOSAMIDE	4	EGFR
SELUMETINIB	4	EGFR
TERFENADINE	4	EGFR
ALECTINIB	4	ALK, EGFR
IBRUTINIB	4	EGFR, ERBB2
AFATINIB DIMALEATE	4	EGFR, ERBB2
CABOZANTINIB	4	EGFR, ERBB2
DACOMITINIB	4	EGFR, ERBB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	9	CHEK1, EGFR, ERBB2, BTN3A1, STK33, CHRNA5, CHRNB4, EPHB1, ALK
B	Phased (≥1) drug, not yet approved	4	RB1, RICTOR, MYC, FUT4
C	Druggable family + PDB, no drug	9	UBE2G1, ALDH1A2, A2ML1, CRTAM, HLA-B, HLA-C, HLA-DQA1, HLA-DRB1, HLA-E
D	Druggable family + AlphaFold only, no drug	5	ADAMTSL1, ADGRV1, FSTL4, SPNS3, VSTM1
E	Difficult family or no structure, no drug	48	SLFN11, RGS6, BMP6, SH3GL2, DST, BRCA2, BAG6, C6orf15, ZNF322P1, SGCZ (+38 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLFN11	6	—
RGS6	0	—
BMP6	1	—
SH3GL2	0	—
DST	0	—
BRCA2	0	—
UBE2G1	0	—
BAG6	1	—
C6orf15	0	—
ZNF322P1	0	—
SGCZ	0	—
BBX	0	—
ADAMTSL1	0	—
ALDH1A2	32	—
FAM167A-AS1	0	—
SKAP2	0	—
IL33	1	—
COL21A1	0	—
ABT1	0	—
ADGRV1	0	—
SFTA2	0	—
PIWIL4	0	—
GUSBP2	0	—
FOXN3	0	—
TMEM179	0	—
HCG4	0	—
FSTL4	0	—
IFITM4P	0	—
SCIN	0	—
A2ML1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 762.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	264
PHASE1	149
Not specified	143
PHASE1/PHASE2	115
PHASE3	70
PHASE2/PHASE3	10
EARLY_PHASE1	7
PHASE4	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06467786	PHASE4	RECRUITING	Study on the Therapeutic Effect of Irinotecan Liposomes in Small Cell Lung Cancer
NCT06951841	PHASE4	NOT_YET_RECRUITING	Prospective, Single-arm, Phase II Clinical Study of Irinotecan Hydrochloride Liposome Injection Combined With Platinum and Immune Checkpoint Inhibitors Combined With Anlotinib for the Maintenance of Extensive Small Cell Lung Cancer After First-line Induction
NCT02348450	PHASE4	UNKNOWN	Irinotecan Plus Cisplatin Compared With Etoposide Plus Cisplatin for Extensive Stage Small-cell Lung Cancer
NCT03890055	PHASE4	UNKNOWN	Clinical Study of First-line Treatment of Small Cell Lung Cancer (SCLC) With Anlotinib Hydrochloride
NCT01064466	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Pharmacogenomics ANDA SNP Clinical Study - Etoposide and Single Nucleotide Polymorphisms
NCT03703297	PHASE3	ACTIVE_NOT_RECRUITING	Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy
NCT04155034	PHASE3	RECRUITING	S1827 (MAVERICK) Testing Whether the Use of Brain Scans Alone Instead of Brain Scans Plus Preventive Brain Radiation Affects Lifespan in Patients With Small Cell Lung Cancer
NCT04624204	PHASE3	ACTIVE_NOT_RECRUITING	Placebo-controlled, Study of Concurrent Chemoradiation Therapy With Pembrolizumab Followed by Pembrolizumab and Olaparib in Newly Diagnosed Treatment-Naïve Limited-Stage Small Cell Lung Cancer (LS-SCLC) (MK 7339-013/KEYLYNK-013)
NCT04665856	PHASE3	ACTIVE_NOT_RECRUITING	Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer
NCT04804644	PHASE3	RECRUITING	Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability
NCT05091567	PHASE3	ACTIVE_NOT_RECRUITING	A Phase III, Open-Label Study of Maintenance Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab in Participants With Extensive-Stage Small-Cell Lung Cancer
NCT05224141	PHASE3	ACTIVE_NOT_RECRUITING	Pembrolizumab/Vibostolimab (MK-7684A) or Atezolizumab in Combination With Chemotherapy in First Line Treatment of Extensive-Stage Small Cell Lung Cancer (MK-7684A-008/KEYVIBE-008)
NCT05740566	PHASE3	ACTIVE_NOT_RECRUITING	Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer
NCT06117774	PHASE3	ACTIVE_NOT_RECRUITING	Study Evaluating Tarlatamab After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer (LS-SCLC)
NCT06203210	PHASE3	RECRUITING	A Study of Ifinatamab Deruxtecan Versus Treatment of Physician’s Choice in Subjects With Relapsed Small Cell Lung Cancer
NCT06211036	PHASE3	ACTIVE_NOT_RECRUITING	Study Comparing Tarlatamab and Durvalumab Versus Durvalumab Alone in First-Line Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) Following Platinum, Etoposide and Durvalumab
NCT06247605	PHASE3	RECRUITING	A Phase IIII Study of AL8326 in Small Cell Lung Cancer
NCT06441344	PHASE3	NOT_YET_RECRUITING	Toripalimab Plus Anlotinib for the Maintenance of Extensive Stage Small Cell
NCT06457906	PHASE3	RECRUITING	SRS/SRT/Hypo-RT Versus HA-WBRT for No More Than 10 Brain Metastases in SCLC
NCT06498479	PHASE3	RECRUITING	ARTEMIS-008：HS-20093 Compared With Topotecan in Subjects With Relapsed Small Cell Lung Cancer
NCT06500026	PHASE3	ACTIVE_NOT_RECRUITING	A Study Comparing BL-B01D1 With Topotecan in Patients With Recurrent Small Cell Lung Cancer(PANKU-Lung03)
NCT06581380	PHASE3	NOT_YET_RECRUITING	JK-1201I Compared with Topotecan in Patients with Relapsed Extensive Stage Small Cell Lung Cancer
NCT06612151	PHASE3	ACTIVE_NOT_RECRUITING	A Phase III Study of YL201 in Relapsed Small Cell Lung Cancer
NCT06616532	PHASE3	ACTIVE_NOT_RECRUITING	PM8002 in Combination With Paclitaxel Compared With Chemotherapy as Second-line Treatment in Small Cell Lung Cancer
NCT06789796	PHASE3	NOT_YET_RECRUITING	a Study of QL1706 or QL1604 in Patients With Limited-stage Small Cell Lung Cancer After Chemoradiotherapy.
NCT06840704	PHASE3	RECRUITING	Immunonutrition Reduces Acute Esophagitis After Thoracic Radiotherapy in Lung Cancer
NCT06992609	PHASE3	RECRUITING	Durvalumab After Chemoradiotherapy in Limited Stage Small Cell Lung Cancer.
NCT07005128	PHASE3	RECRUITING	A Study Comparing Tarlatamab, Durvalumab, Carboplatin, and Etoposide Versus Durvalumab, Carboplatin, and Etoposide in First-line Extensive Stage Small-Cell Lung Cancer (ES-SCLC)
NCT07010263	PHASE3	RECRUITING	A Study of AK112 as Consolidation Treatment for Patients With Limited Stage Small-cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy
NCT07015892	PHASE3	RECRUITING	Dose-Escalation Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized Trial
NCT07106528	PHASE2/PHASE3	NOT_YET_RECRUITING	Organoid-guided vs Topotecan Therapy in Relapsed Extensive-Stage Small Cell Lung Cancer
NCT07145333	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Pharmacogenomics ANDA SNP Clinical Study - Topotecan and Single Nucleotide Polymorphisms
NCT07189455	PHASE3	RECRUITING	Study Comparing ZG006 With Investigator-Selected Chemotherapy in Participants With Relapsed Small Cell Lung Cancer
NCT07218146	PHASE3	RECRUITING	A Study of ZL-1310 Versus Investigator’s Choice of Therapy in Participants With Relapsed Small Cell Lung Cancer (DLLEVATE)
NCT07226999	PHASE2/PHASE3	RECRUITING	Symbiotic-Lung-04: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Extensive-Stage Small Cell Lung Cancer
NCT07365241	PHASE3	NOT_YET_RECRUITING	A Study to Evaluate Adverse Events and Change in Disease Activity of Intravenous ABBV-706 Versus Standard of Care in Adult Participants With Relapsed/Refractory Small Cell Lung Cancer
NCT07472517	PHASE3	RECRUITING	DAREON ® -Lung-1: A Study in People With Advanced Small Cell Lung Cancer to Compare Obrixtamig Plus Atezolizumab, Carboplatin, and Etoposide Treatment With Standard Chemotherapy
NCT00043927	PHASE3	COMPLETED	Extensive Small Cell Lung Cancer Treatment Using An Investigational Drug Plus Chemotherapy In Chemotherapy-Naive Adults
NCT00119613	PHASE3	COMPLETED	A Study of Subjects With Previously Untreated Extensive-Stage Small-Cell Lung Cancer (SCLC) Treated With Platinum Plus Etoposide Chemotherapy With or Without Darbepoetin Alfa
NCT00143455	PHASE3	COMPLETED	Study Of Irinotecan Hydrochloride (Campto(R)) And Cisplatin Versus Etoposide And Cisplatin In Small Cell Lung Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CISPLATIN	4	50
TOPOTECAN	4	27
IRINOTECAN	4	20
LURBINECTEDIN	4	17
TARLATAMAB	4	12
ATEZOLIZUMAB	4	6
DURVALUMAB	4	4
TISLELIZUMAB	4	4
MEMANTINE	4	3
TORIPALIMAB	4	3
IPILIMUMAB	4	2
PEMETREXED	4	2
TREMELIMUMAB	4	2
DARBEPOETIN ALFA	4	1
DINUTUXIMAB	4	1
ETOPOSIDE	4	1
PEMBROLIZUMAB	4	1
VINCRISTINE	4	1
CATEQUENTINIB	3	24
AMRUBICIN	3	17
ROVALPITUZUMAB TESIRINE	3	11
PLATINUM	3	8
IBCASERTIB	3	4
RIVOCERANIB	3	4
IFINATAMAB DERUXTECAN	3	2
PICOPLATIN	3	2
TIRAGOLUMAB	3	2
REMINERTANT	3	1
CHEMBL5397028	0	17
CHEMBL5412235	0	6

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 10 predictive associations from 11 curated evidence items; also 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
DLL3 Expression	Rovalpituzumab Tesirine	Sensitivity/Response	CIViC B	EID5919 +1
RB1 Mutation	Chemotherapy	Sensitivity/Response	CIViC B	EID1866
ERBB2 Amplification	Irinotecan + Trastuzumab	Sensitivity/Response	CIViC C	EID1044
RICTOR Amplification	Vistusertib	Sensitivity/Response	CIViC C	EID7449
CHEK1 Overexpression	Prexasertib + Cisplatin + Olaparib	Sensitivity/Response	CIViC D	EID4874
EGFR L858R	Erlotinib	Sensitivity/Response	CIViC D	EID4293
MYC Overexpression	Olaparib + Cisplatin + Prexasertib	Sensitivity/Response	CIViC D	EID3003
RICTOR Amplification	Vistusertib + MTOR Kinase Inhibitor AZD8055 + Sapanisertib	Sensitivity/Response	CIViC D	EID1916
SLFN11 EXPRESSION	Temozolomide + Talazoparib	Sensitivity/Response	CIViC D	EID5883
YES1 Overexpression OR YES1 Amplification	CH6953755 + Dasatinib	Sensitivity/Response	CIViC D	EID12556