Nonpapillary renal cell carcinoma

Summary

Nonpapillary renal cell carcinoma (MONDO:0007763) is a cancer with 24 cohort genes (19 CIViC-evidence somatic drivers; 578 ClinVar predisposition records) and 1,139 clinical trials. Molecularly, TSC1 Loss-of-function confers sensitivity to MTOR Inhibitor in Renal Cell Carcinoma (CIViC Level B); 33 further subtype–drug associations are mapped below. Top therapeutic interventions include sunitinib, sorafenib, and cabozantinib.

At a glance

• Classification: Cancer
• Cohort genes: 24
• ClinVar variants: 578
• Clinical trials: 1,139
• Precision-medicine evidence (CIViC): 34 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nonpapillary renal cell carcinoma
Mondo ID	MONDO:0007763
OMIM	144700
DOID	DOID:0050387
GARD	0024575
Is cancer (heuristic)	yes

Also known as: CCRCC · clear cell renal cell adenocarcinoma · clear cell renal cell carcinoma · RCC · renal carcinoma, chromophobe, somatic · renal cell carcinoma · renal cell carcinoma, clear cell · renal cell carcinoma, clear cell, somatic · renal cell carcinoma, nonpapillary · renal cell carcinoma, somatic

Data availability: 578 ClinVar variants · 4 GenCC gene-disease records · 529 cell lines · 23 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 › adenocarcinoma › renal cell carcinoma › nonpapillary renal cell carcinoma

Related subtypes (10): mucinous tubular and spindle renal cell carcinoma, renal pelvis adenocarcinoma, Wolffian duct adenocarcinoma, collecting duct carcinoma, renal cell adenocarcinoma, cystic renal cell carcinoma, kidney medullary carcinoma, adrenal cortex carcinoma, MIT family translocation renal cell carcinoma, acquired cystic disease-associated renal cell carcinoma

Subtypes (2): clear cell renal carcinoma, clear cell papillary renal cell carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

578 retrieved; paginated sample, class counts are floors:

241 uncertain significance, 161 conflicting classifications of pathogenicity, 55 benign/likely benign, 29 pathogenic/likely pathogenic, 28 pathogenic, 23 likely pathogenic, 17 likely benign, 17 benign, 7 uncertain significance/uncertain risk allele

ClinVar	Variant (HGVS)	Gene	Classification	Review
1381774	NM_144997.7(FLCN):c.970C>T (p.Gln324Ter)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141865	NM_144997.7(FLCN):c.499C>T (p.Gln167Ter)	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
186785	NM_144997.7(FLCN):c.466TTC[1] (p.Phe157del)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
231274	NM_144997.7(FLCN):c.779+1G>T	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
233744	NM_144997.7(FLCN):c.189del (p.Ala64fs)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
241922	NM_144997.7(FLCN):c.347dup (p.Leu117fs)	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
253251	NM_144997.7(FLCN):c.1429C>T (p.Arg477Ter)	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
253252	NM_144997.7(FLCN):c.1432+1G>A	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253259	NM_144997.7(FLCN):c.1579_1580insA (p.Arg527fs)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265154	NM_144997.7(FLCN):c.1062+2T>G	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
265155	NM_144997.7(FLCN):c.1601del (p.Lys534fs)	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
3363	NM_144997.7(FLCN):c.1285dup (p.His429fs)	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
3364	NM_144997.7(FLCN):c.1285del (p.His429fs)	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
3382013	NM_144997.7(FLCN):c.636del (p.Gln212fs)	FLCN	Pathogenic	criteria provided, single submitter
3581694	NM_144997.7(FLCN):c.1372dup (p.Gln458fs)	FLCN	Pathogenic	criteria provided, single submitter
428647	NM_144997.7(FLCN):c.1657T>C (p.Trp553Arg)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428656	NM_144997.7(FLCN):c.44dup (p.Arg17fs)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428658	NM_144997.7(FLCN):c.1357_1363del (p.Gly453fs)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
96478	NM_144997.7(FLCN):c.1533G>A (p.Trp511Ter)	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
96481	NM_144997.7(FLCN):c.250-2A>G	FLCN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
96482	NM_144997.7(FLCN):c.296del (p.Asp99fs)	FLCN	Pathogenic	criteria provided, multiple submitters, no conflicts
14928	NM_000545.8(HNF1A):c.1340C>T (p.Pro447Leu)	HNF1A	Pathogenic	reviewed by expert panel
1693221	NM_000545.8(HNF1A):c.1556C>T (p.Pro519Leu)	HNF1A	Pathogenic	reviewed by expert panel
3574303	NM_000545.8(HNF1A):c.1456C>T (p.Gln486Ter)	HNF1A	Pathogenic	criteria provided, single submitter
36824	NM_000545.5(HNF1A):c.598C>T (p.Arg200Trp)	HNF1A	Pathogenic	reviewed by expert panel
372380	NM_000545.8(HNF1A):c.526C>T (p.Gln176Ter)	HNF1A	Pathogenic	reviewed by expert panel
379138	NM_000545.8(HNF1A):c.788G>A (p.Arg263His)	HNF1A	Pathogenic	reviewed by expert panel
420064	NM_000545.8(HNF1A):c.685C>T (p.Arg229Ter)	HNF1A	Pathogenic	reviewed by expert panel
447503	NM_000545.8(HNF1A):c.814C>T (p.Arg272Cys)	HNF1A	Pathogenic	reviewed by expert panel
562373	NM_000545.8(HNF1A):c.392G>A (p.Arg131Gln)	HNF1A	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 75 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
HNF1A	LoF	HCC,PRCC
VHL	LoF	CCRCC,PGNG,RCC	CIViC #58
FLCN	LoF	LUAD	CIViC #19959
PBRM1	LoF	CCRCC,CEAD,CHOL,COADREAD,ESCA,GBC,LUAD,MEL,NSCLC,PLMESO,PRCC,RCC,SKCM,STAD,UCEC	CIViC #62
RNF2	LoF	BRCA,CCRCC,CESC,CHOL,ESCA,HCC,PANCREAS,PLMESO,PRCC,RCC,SACA,SKCM,STAD,UM	CIViC #70
ARID1A	LoF	BL,BLCA,BRCA,CCRCC,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,GBC,GBM,HCC,LGGNOS,LUAD,LUNG,LUSC,MBL,MLYM,MT,NHL,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PRAD,RCC,SCLC,SKIN,STAD,UCEC,UCS,UTUC	CIViC #6559
TSC1	LoF	BLCA,BRCA,COADREAD,HCC,LUAD,RCC,SKCM,STAD,UTUC	CIViC #46
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
FBXW7	LoF	ANSC,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HNSC,LUAD,LUSC,MBL,NETNOS,NPC,PAAD,PAST,READ,STAD,UCEC,UCS	CIViC #12903
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
EPAS1	Act	PGNG	CIViC #1705
KLLN			CIViC #32083
FLT3	Act	ALL,AML	CIViC #24
MTOR	Act	BLCA,BRCA,CCRCC,CHRCC,CLLSLL,COADREAD,HCC,LGGNOS,PANET,RCC,UCEC	CIViC #2073
GNAS	Act	BRCA,COADREAD,ESCA,HCC,LUAD,MBL,PAAD,PANCREAS	CIViC #2319
HIF1A	Act	WDTC	CIViC #2596
HMOX1			CIViC #2657
B4GALT1			CIViC #2239

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
OGG1	Limited	Autosomal dominant	nonpapillary renal cell carcinoma
RNF139	Limited	Autosomal dominant	nonpapillary renal cell carcinoma	2
HNF1A	No Known Disease Relationship	Unknown	nonpapillary renal cell carcinoma	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HNF1A	Orphanet:319303	Chromophobe renal cell carcinoma
HNF1A	Orphanet:324575	Hyperinsulinism due to HNF1A deficiency
HNF1A	Orphanet:404511	Clear cell papillary renal cell carcinoma
HNF1A	Orphanet:552	MODY
VHL	Orphanet:238557	Chuvash erythrocytosis
VHL	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
VHL	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
VHL	Orphanet:892	Von Hippel-Lindau disease
RNF139	Orphanet:422526	Hereditary clear cell renal cell carcinoma
FLCN	Orphanet:122	Birt-Hogg-Dubé syndrome
FLCN	Orphanet:2903	Familial spontaneous pneumothorax
FLCN	Orphanet:422526	Hereditary clear cell renal cell carcinoma
PBRM1	Orphanet:404511	Clear cell papillary renal cell carcinoma
RNF2	Orphanet:528084	Non-specific syndromic intellectual disability
ARID1A	Orphanet:1465	Coffin-Siris syndrome
TSC1	Orphanet:210159	Adult hepatocellular carcinoma
TSC1	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC1	Orphanet:538	Lymphangioleiomyomatosis
TSC1	Orphanet:805	Tuberous sclerosis complex
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
FBXW7	Orphanet:528084	Non-specific syndromic intellectual disability
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
CDKN2B	Orphanet:618	Familial melanoma
CDKN2B	Orphanet:652	Multiple endocrine neoplasia type 1
EPAS1	Orphanet:247511	Autosomal dominant secondary polycythemia
EPAS1	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
EPAS1	Orphanet:324299	Multiple paragangliomas associated with polycythemia
KLLN	Orphanet:201	Cowden syndrome
KLLN	Orphanet:227535	Hereditary breast cancer
FLT3	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
FLT3	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
FLT3	Orphanet:589534	Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2)
FLT3	Orphanet:589595	Mixed phenotype acute leukemia with t(v;11q23.3)
FLT3	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
FLT3	Orphanet:98832	Acute myeloid leukemia with minimal differentiation
FLT3	Orphanet:98833	Acute myeloblastic leukemia without maturation
FLT3	Orphanet:98834	Acute myeloblastic leukemia with maturation
FLT3	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
MTOR	Orphanet:269001	Isolated focal cortical dysplasia type IIa
MTOR	Orphanet:269008	Isolated focal cortical dysplasia type IIb

Cohort genes → proteins

24 cohort genes, 24 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	15
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	gencc,clinvar
VHL	HGNC:12687	ENSG00000134086	P40337	von Hippel-Lindau disease tumor suppressor	clinvar,civic_evidence
RNF139	HGNC:17023	ENSG00000170881	Q8WU17	E3 ubiquitin-protein ligase RNF139	gencc,clinvar
FLCN	HGNC:27310	ENSG00000154803	Q8NFG4	Folliculin	clinvar,civic_evidence
PBRM1	HGNC:30064	ENSG00000163939	Q86U86	Protein polybromo-1	clinvar,civic_evidence
RNF2	HGNC:10061	ENSG00000121481	Q99496	E3 ubiquitin-protein ligase RING2	civic_evidence
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	civic_evidence
TSC1	HGNC:12362	ENSG00000165699	Q92574	Hamartin	civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
FBXW7	HGNC:16712	ENSG00000109670	Q969H0	F-box/WD repeat-containing protein 7	civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	civic_evidence
EPAS1	HGNC:3374	ENSG00000116016	Q99814	Endothelial PAS domain-containing protein 1	civic_evidence
KLLN	HGNC:37212	ENSG00000227268	B2CW77	Killin	civic_evidence
FLT3	HGNC:3765	ENSG00000122025	P36888	Receptor-type tyrosine-protein kinase FLT3	civic_evidence
MTOR	HGNC:3942	ENSG00000198793	P42345	Serine/threonine-protein kinase mTOR	civic_evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence
HIF1A	HGNC:4910	ENSG00000100644	Q16665	Hypoxia-inducible factor 1-alpha	civic_evidence
HMOX1	HGNC:5013	ENSG00000100292	P09601	Heme oxygenase 1	civic_evidence
OGG1	HGNC:8125	ENSG00000114026	O15527	N-glycosylase/DNA lyase	gencc
B4GALT1	HGNC:924	ENSG00000086062	P15291	Beta-1,4-galactosyltransferase 1	civic_evidence
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	clinvar
CAMK1	HGNC:1459	ENSG00000134072	Q14012	Calcium/calmodulin-dependent protein kinase type 1	clinvar
C12orf43	HGNC:25719	ENSG00000157895	Q96C57	Protein CUSTOS	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
VHL	von Hippel-Lindau disease tumor suppressor	Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
RNF139	E3 ubiquitin-protein ligase RNF139	E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death.
FLCN	Folliculin	Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis.
PBRM1	Protein polybromo-1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
RNF2	E3 ubiquitin-protein ligase RING2	E3 ubiquitin-protein ligase that mediates monoubiquitination of ‘Lys-119’ of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation.
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
TSC1	Hamartin	Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
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.
FBXW7	F-box/WD repeat-containing protein 7	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
EPAS1	Endothelial PAS domain-containing protein 1	Transcription factor involved in the induction of oxygen regulated genes.
KLLN	Killin	DNA-binding protein involved in S phase checkpoint control-coupled apoptosis by mediating p53/TP53-induced apoptosis.
FLT3	Receptor-type tyrosine-protein kinase FLT3	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells.
MTOR	Serine/threonine-protein kinase mTOR	Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
HIF1A	Hypoxia-inducible factor 1-alpha	Functions as a master transcriptional regulator of the adaptive response to hypoxia.
HMOX1	Heme oxygenase 1	Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.
OGG1	N-glycosylase/DNA lyase	DNA repair enzyme that incises DNA at 8-oxoG residues.
B4GALT1	Beta-1,4-galactosyltransferase 1	Galactosyltransferase acting in the Golgi stacks.
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3’.
CAMK1	Calcium/calmodulin-dependent protein kinase type 1	Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, a…
C12orf43	Protein CUSTOS	Plays a role in the regulation of Wnt signaling pathway during early development.

Protein-family classification

Druggable: 7 · Difficult: 9 · Unknown: 8 · 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
Kinase	3	3.5×	0.155
Transcription factor	6	2.1×	0.155
Scaffold/PPI	3	2.2×	0.199
Enzyme (other)	4	2.0×	0.199
Other/Unknown	8	0.6×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
VHL	Enzyme (other)	yes	2.3.2.B13	VHL_tumour_suppress_b/a_dom, VHL_alpha_dom, VHL_beta_dom
RNF139	Transcription factor	no		Znf_RING, Znf_RING-CH, Znf_RING/FYVE/PHD
FLCN	Other/Unknown	no		Folliculin, Folliculin_DENN, Folliculin/SMCR8_longin
PBRM1	Other/Unknown	no		BAH_dom, Bromodomain, HMG_box_dom
RNF2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold
TSC1	Other/Unknown	no		Hamartin
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
FBXW7	Scaffold/PPI	no		WD40_rpt, F-box_dom, WD40/YVTN_repeat-like_dom_sf
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
EPAS1	Transcription factor	no		PAS, Nuc_translocat, PAC
KLLN	Other/Unknown	no
FLT3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
MTOR	Kinase	yes		PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
HIF1A	Transcription factor	no		PAS, HIF-1_alpha, PAC
HMOX1	Enzyme (other)	yes	1.14.14.18	Haem_Oase, Haem_Oase-like, Haem_Oase-like_multi-hlx
OGG1	Enzyme (other)	yes	3.2.2.23	HhH-GPD_domain, Ogg1, DNA_glycosylase
B4GALT1	Enzyme (other)	yes	2.4.1.133	Galactosyl_T, Galactosyl_T_C, Galactosyl_T_N
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
CAMK1	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
C12orf43	Other/Unknown	no		CUSTOS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	24
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	4
cerebellar hemisphere	3
ganglionic eminence	3
monocyte	2
buccal mucosa cell	2
right hemisphere of cerebellum	2
primordial germ cell in gonad	2
ventricular zone	2
stromal cell of endometrium	2
male germ line stem cell (sensu Vertebrata) in testis	2
pancreatic ductal cell	2
liver	1
mucosa of transverse colon	1
right lobe of liver	1
mononuclear cell	1
left testis	1
male germ cell	1
sperm	1
amniotic fluid	1
bone marrow cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HNF1A	81	tissue_specific	yes	right lobe of liver, mucosa of transverse colon, liver
VHL	186	ubiquitous	marker	cortical plate, monocyte, mononuclear cell
RNF139	294	ubiquitous	marker	sperm, male germ cell, left testis
FLCN	261	ubiquitous	marker	buccal mucosa cell, right hemisphere of cerebellum, cerebellar hemisphere
PBRM1	289	ubiquitous	marker	cortical plate, ganglionic eminence, amniotic fluid
RNF2	178	ubiquitous	marker	primordial germ cell in gonad, cortical plate, ganglionic eminence
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo
TSC1	297	ubiquitous	marker	substantia nigra pars compacta, gluteal muscle, lateral globus pallidus
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
FBXW7	290	ubiquitous	marker	Brodmann (1909) area 23, calcaneal tendon, colonic epithelium
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
EPAS1	298	ubiquitous	marker	right lung, lower lobe of lung, adult organism
KLLN	149		marker	tibialis anterior, male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell
FLT3	166	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex
MTOR	207	ubiquitous	marker	primordial germ cell in gonad, right hemisphere of cerebellum, cerebellar hemisphere
GNAS	312	ubiquitous	marker	type B pancreatic cell, postcentral gyrus, Brodmann (1909) area 46
HIF1A	295	ubiquitous	marker	pancreatic ductal cell, epithelial cell of pancreas, corpus epididymis
HMOX1	230	ubiquitous	marker	cartilage tissue, spleen, monocyte
OGG1	288	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
B4GALT1	276	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, left uterine tube
HNF1B	74	broad	marker	metanephros cortex, adult mammalian kidney, kidney
CAMK1	208	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland cortex
C12orf43	266	ubiquitous	marker	secondary oocyte, oocyte, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 17.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HIF1A	9,734
MTOR	9,490
CDKN2A	9,311
CCND1	8,328
FBXW7	7,956
TSC1	5,445
EPAS1	4,652
HMOX1	4,054
RNF2	3,814
FLT3	3,570

Intra-cohort edges

A	B	Sources
ARID1A	PBRM1	string_interaction
B4GALT1	TSC1	biogrid_interaction
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	CDKN2B	string_interaction
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	HIF1A	string_interaction
EPAS1	HIF1A	string_interaction
EPAS1	VHL	biogrid_interaction, intact, string_interaction
FLCN	KLLN	string_interaction
FLCN	MTOR	string_interaction
FLT3	VHL	biogrid_interaction
HIF1A	VHL	biogrid_interaction, intact, string_interaction
HNF1A	HNF1B	biogrid_interaction, intact, string_interaction
MTOR	TSC1	string_interaction
PBRM1	VHL	biogrid_interaction
RNF139	VHL	intact
TSC1	VHL	biogrid_interaction

Structural data

PDB: 20 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAS	O95467	490
VHL	P40337	142
MTOR	P42345	70
OGG1	O15527	47
EPAS1	Q99814	43
PBRM1	Q86U86	30
HMOX1	P09601	26
HIF1A	Q16665	25
B4GALT1	P15291	19
RNF2	Q99496	15
CCND1	P24385	11
FLT3	P36888	11
ARID1A	O14497	7
FBXW7	Q969H0	7
HNF1A	P20823	6
TSC1	Q92574	5
CDKN2A	P42771	5
FLCN	Q8NFG4	4
CAMK1	Q14012	4
HNF1B	P35680	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDKN2B	P42772	90.12
RNF139	Q8WU17	79.88
C12orf43	Q96C57	64.08
KLLN	B2CW77	51.20

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 261. Enrichment computed across 24 evidence-associated genes (22 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 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PTK6 Expression	2	173.0×	0.005	EPAS1, HIF1A
G1 Phase	3	53.7×	0.005	CCND1, CDKN2A, CDKN2B
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	3	41.0×	0.005	PBRM1, RNF2, ARID1A
RUNX3 regulates p14-ARF	2	103.8×	0.007	CCND1, CDKN2A
Regulation of gene expression by Hypoxia-inducible Factor	2	86.5×	0.007	EPAS1, HIF1A
Cyclin D associated events in G1	3	31.8×	0.007	CCND1, CDKN2A, CDKN2B
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	3	26.9×	0.007	VHL, EPAS1, HIF1A
Mitotic G1 phase and G1/S transition	3	25.1×	0.007	CCND1, CDKN2A, CDKN2B
MITF-M-dependent gene expression	3	24.7×	0.007	ARID1A, CCND1, CDKN2A
Cellular response to hypoxia	2	79.9×	0.007	EPAS1, HIF1A
RMTs methylate histone arginines	3	20.0×	0.010	PBRM1, ARID1A, CCND1
Defective B4GALT1 causes CDG-2d	1	519.1×	0.012	B4GALT1
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	519.1×	0.012	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	519.1×	0.012	CDKN2A
Defective OGG1 Substrate Binding	1	519.1×	0.012	OGG1
Defective OGG1 Substrate Processing	1	519.1×	0.012	OGG1
Defective OGG1 Localization	1	519.1×	0.012	OGG1
FLT3 mutants bind TKIs	1	519.1×	0.012	FLT3
KW2449-resistant FLT3 mutants	1	519.1×	0.012	FLT3
semaxanib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
crenolanib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
gilteritinib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
lestaurtinib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
midostaurin-resistant FLT3 mutants	1	519.1×	0.012	FLT3
pexidartinib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
ponatinib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
quizartinib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
sorafenib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
sunitinib-resistant FLT3 mutants	1	519.1×	0.012	FLT3
tandutinib-resistant FLT3 mutants	1	519.1×	0.012	FLT3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of macroautophagy	3	140.4×	2e-04	TSC1, MTOR, HMOX1
regulation of G1/S transition of mitotic cell cycle	4	51.1×	2e-04	PBRM1, ARID1A, CDKN2A, CDKN2B
cellular response to hypoxia	5	25.3×	2e-04	VHL, CCND1, EPAS1, MTOR, HIF1A
TOR signaling	3	95.8×	5e-04	FLCN, MTOR, HIF1A
regulation of G0 to G1 transition	3	84.3×	6e-04	PBRM1, ARID1A, CDKN2B
negative regulation of TOR signaling	3	70.2×	7e-04	FLCN, TSC1, HIF1A
positive regulation of ubiquitin-dependent protein catabolic process	3	70.2×	7e-04	RNF139, FBXW7, MTOR
negative regulation of lysosome organization	2	351.1×	7e-04	FLCN, MTOR
negative regulation of cell population proliferation	6	10.5×	9e-04	VHL, RNF139, PBRM1, TSC1, CDKN2A, CDKN2B
protein stabilization	5	13.9×	0.001	VHL, TSC1, FBXW7, CDKN2A, MTOR
cellular response to nutrient	2	175.5×	0.002	CDKN2B, MTOR
epithelial cell proliferation	3	39.0×	0.003	FLCN, HNF1B, B4GALT1
protein destabilization	3	36.3×	0.003	RNF139, CDKN2A, MTOR
negative regulation of epithelial cell proliferation	3	36.3×	0.003	FLCN, CDKN2B, B4GALT1
negative regulation of cell size	2	140.4×	0.003	TSC1, MTOR
intracellular oxygen homeostasis	2	127.7×	0.003	EPAS1, HIF1A
mammary gland epithelial cell proliferation	2	127.7×	0.003	CCND1, CDKN2A
positive regulation of cell differentiation	3	33.4×	0.003	VHL, PBRM1, ARID1A
positive regulation of DNA-templated transcription	6	7.0×	0.004	HNF1A, VHL, ARID1A, HNF1B, CDKN2A, HIF1A
cellular response to starvation	3	24.2×	0.006	FLCN, TSC1, MTOR
response to iron ion	2	78.0×	0.007	CCND1, HIF1A
regulation of protein neddylation	2	78.0×	0.007	EPAS1, HIF1A
obsolete D-glucose import	2	70.2×	0.008	HNF1A, TSC1
embryonic placenta development	2	63.8×	0.009	EPAS1, HIF1A
vascular endothelial cell response to laminar fluid shear stress	2	61.1×	0.010	MTOR, GNAS
pancreas development	2	56.2×	0.011	HNF1A, HNF1B
positive regulation of glycolytic process	2	56.2×	0.011	MTOR, HIF1A
amyloid fibril formation	2	50.1×	0.012	VHL, CDKN2A
regulation of nucleotide-excision repair	2	50.1×	0.012	PBRM1, ARID1A
intracellular glucose homeostasis	2	48.4×	0.012	GNAS, HIF1A

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 16

Druggability breadth: 16 of 24 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

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

Symbol	Example approved molecule
VHL	OSIMERTINIB
CCND1	PALBOCICLIB
EPAS1	BELZUTIFAN
FLT3	PONATINIB
MTOR	SALMETEROL XINAFOATE
HIF1A	EMETINE
CAMK1	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HIF1A	255	4
MTOR	164	4
FLT3	143	4
CCND1	35	4
CAMK1	19	4
VHL	7	4
EPAS1	7	4
PBRM1	2	2
HNF1A	0	0
RNF139	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OSIMERTINIB	4	VHL
BRIGATINIB	4	FLT3, VHL
CRIZOTINIB	4	FLT3, VHL
ADAGRASIB	4	VHL
PALBOCICLIB	4	CCND1, FLT3
ABEMACICLIB	4	CCND1, FLT3
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
BELZUTIFAN	4	EPAS1
EMETINE	4	EPAS1, HIF1A, MTOR
DOXORUBICIN	4	EPAS1, HIF1A
TOPOTECAN	4	EPAS1, HIF1A
PONATINIB	4	FLT3
AFATINIB	4	FLT3
FEDRATINIB	4	CAMK1, FLT3
TIVOZANIB	4	FLT3
AXITINIB	4	FLT3
SORAFENIB	4	FLT3
NERATINIB	4	FLT3
INFIGRATINIB PHOSPHATE	4	FLT3
INFIGRATINIB	4	FLT3
IBRUTINIB	4	FLT3
REGORAFENIB	4	FLT3
ENTRECTINIB	4	FLT3
PACRITINIB	4	FLT3
FOSTAMATINIB	4	FLT3
QUIZARTINIB DIHYDROCHLORIDE	4	FLT3
CABOZANTINIB	4	FLT3
CERITINIB	4	FLT3
VANDETANIB	4	FLT3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
VHL	3,575	Binding:3482, Functional:54, ADMET:39
FLT3	3,132	Binding:3096, Functional:24, ADMET:8, Toxicity:4
MTOR	1,375	Binding:1335, Functional:37, ADMET:2, Toxicity:1
CCND1	576	Binding:574, Functional:1, ADMET:1
HIF1A	427	Binding:411, Functional:16
CAMK1	324	Binding:322, Functional:2
EPAS1	241	Binding:233, Functional:8
PBRM1	193	Binding:193
HMOX1	23	Binding:22, ADMET:1
OGG1	19	Binding:18, Functional:1
RNF2	16	Binding:16
B4GALT1	9	Binding:9
ARID1A	6	Binding:6
CDKN2A	2	Binding:2
HNF1A	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
VHL	2.3.2.B13
RNF2	2.3.2.27	RING-type E3 ubiquitin transferase
FLT3	2.7.10.1	receptor protein-tyrosine kinase
HMOX1	1.14.14.18	heme oxygenase (biliverdin-producing)
OGG1	3.2.2.23, 4.2.99.18	DNA-formamidopyrimidine glycosylase, DNA-(apurinic or apyrimidinic site) lyase
B4GALT1	2.4.1.133, 2.4.1.22, 2.4.1.38, 2.4.1.90	xylosylprotein 4-beta-galactosyltransferase, lactose synthase, beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase, N-acetyllactosamine synthase
CAMK1	2.7.11.17	Ca2+/calmodulin-dependent protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
VHL	3,575
PBRM1	193
CCND1	576
EPAS1	241
FLT3	3,132
MTOR	1,375
HIF1A	427
CAMK1	324

Pharmacogenomics

Cohort genes with a PharmGKB record: 24; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

25 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)
OSIMERTINIB	4	VHL
BRIGATINIB	4	FLT3, VHL
CRIZOTINIB	4	FLT3, VHL
ADAGRASIB	4	VHL
PALBOCICLIB	4	CCND1, FLT3
ABEMACICLIB	4	CCND1, FLT3
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
EMETINE	4	EPAS1, HIF1A, MTOR
DOXORUBICIN	4	EPAS1, HIF1A
TOPOTECAN	4	EPAS1, HIF1A
PONATINIB	4	FLT3
AFATINIB	4	FLT3
FEDRATINIB	4	CAMK1, FLT3
NERATINIB	4	FLT3
INFIGRATINIB PHOSPHATE	4	FLT3
INFIGRATINIB	4	FLT3
IBRUTINIB	4	FLT3
REGORAFENIB	4	FLT3
ENTRECTINIB	4	FLT3
PACRITINIB	4	FLT3
FOSTAMATINIB	4	FLT3
QUIZARTINIB DIHYDROCHLORIDE	4	FLT3
CERITINIB	4	FLT3
VANDETANIB	4	FLT3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	VHL, CCND1, EPAS1, FLT3, MTOR, HIF1A, CAMK1
B	Phased (≥1) drug, not yet approved	1	PBRM1
C	Druggable family + PDB, no drug	3	HMOX1, OGG1, B4GALT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	13	HNF1A, RNF139, FLCN, RNF2, ARID1A, TSC1, FBXW7, CDKN2A, CDKN2B, KLLN (+3 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FLCN	0	MTOR
ARID1A	6	PBRM1
TSC1	0	MTOR
HNF1A	1	—
RNF139	0	—
RNF2	16	—
FBXW7	0	—
CDKN2A	2	—
CDKN2B	0	—
KLLN	0	—
GNAS	0	—
HMOX1	23	—
OGG1	19	—
B4GALT1	9	—
HNF1B	0	—
C12orf43	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,139.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	338
Not specified	291
PHASE1	235
PHASE1/PHASE2	132
PHASE3	65
EARLY_PHASE1	20
PHASE4	12
PHASE2/PHASE3	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07028125	PHASE4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00414765	PHASE4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	PHASE4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	PHASE4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	PHASE4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	PHASE4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	PHASE4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	PHASE4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	PHASE4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT01224288	PHASE3	ACTIVE_NOT_RECRUITING	Dynamic Contrast Enhancement Computed Tomography for Evaluating Tumor Perfusion in Patients With Metastatic Renal Cell Carcinoma Receiving Targeted Therapies: Renal Cell Carcinoma (RCC) Scramble
NCT01575548	PHASE3	ACTIVE_NOT_RECRUITING	Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer Who Have No Evidence of Disease After Surgery
NCT02811861	PHASE3	ACTIVE_NOT_RECRUITING	Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
NCT03055013	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
NCT03141177	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
NCT03288532	PHASE3	RECRUITING	Renal Adjuvant MultiPle Arm Randomised Trial
NCT03592472	PHASE3	RECRUITING	A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV)
NCT03793166	PHASE3	ACTIVE_NOT_RECRUITING	Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study
NCT03873402	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Participants With Advanced Kidney Cancer
NCT03937219	PHASE3	ACTIVE_NOT_RECRUITING	Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
NCT04510597	PHASE3	RECRUITING	Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial
NCT04810078	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread
NCT05078047	PHASE3	RECRUITING	Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO
NCT05219318	PHASE3	ACTIVE_NOT_RECRUITING	Treatment Pause Versus Treatment Continuation in IMDC Good or Intermediate Risk With Only One Adverse Prognostic Factor in mRCC Patients With an Objective Response at 12 Months of Treatment With PD1/ PDL1 ICIs + VEGFR-Tyrosine Kinase Inhibitors
NCT05522231	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Fruquintinib in Combination With Sintilimab in Advanced Renal Cell Carcinoma (FRUSICA-2)
NCT05738694	PHASE3	RECRUITING	Neoadjuvant of Axitinib Plus PD-1 to Improve Disease Free Survival of Patients With Renal Cell Carcinoma
NCT05770037	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 01: Alectinib in Adult, Paediatric and Teenage/Young Adult Patients With ALK Positive Cancers
NCT05796973	PHASE3	RECRUITING	Measuring Oncological Value of Exercise and Statin
NCT05863351	PHASE3	ACTIVE_NOT_RECRUITING	Focused Radiation Versus Systemic Therapy for Kidney Cancer Patients With Limited Metastasis, SOAR Study
NCT06500455	PHASE3	RECRUITING	Testing Longer Duration Radiation Therapy Versus the Usual Radiation Therapy in Patients With Cancer That Has Spread to the Brain
NCT06661720	PHASE3	RECRUITING	Testing the Addition of the Anti-Cancer Drug Tivozanib to Immunotherapy (Pembrolizumab) After Surgery to Remove All Known Sites of Kidney Cancer
NCT06726421	PHASE3	RECRUITING	Systemic Therapy Alone or With Stereotactic Body Radiotherapy for Oligometastatic Kidney Cancer (STROKER Study)
NCT06750419	PHASE3	RECRUITING	89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP Study
NCT07000149	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Investigate the Efficacy and Safety of Volrustomig ± Casdatifan vs Nivolumab + Ipilimumab as 1L Treatment for Advanced ccRCC
NCT07011719	PHASE3	RECRUITING	Study of Casdatifan and Cabozantinib Versus Placebo and Cabozantinib in Patients With Advanced Clear Cell Renal Cell Carcinoma
NCT07165418	PHASE3	NOT_YET_RECRUITING	A Comparison of Vorolanib Tablets Combined With Everolimus Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma Who Have Progressed After Treatment With Immunotherapy Monotherapy or in Combination With TKI
NCT07197580	PHASE3	RECRUITING	Phase 3 Study to Assess Safety and Efficacy of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC
NCT07227402	PHASE3	RECRUITING	A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SUNITINIB	4	34
SORAFENIB	4	30
CABOZANTINIB	4	27
PAZOPANIB	4	22
AXITINIB	4	20
TIVOZANIB	4	19
ALDESLEUKIN	4	13
BELZUTIFAN	4	12
NIVOLUMAB	4	10
IPILIMUMAB	4	8
TEMSIROLIMUS	4	8
EVEROLIMUS	4	5
LENVATINIB	4	5
TREMELIMUMAB	4	5
PEMBROLIZUMAB	4	4
ATEZOLIZUMAB	4	3
AVELUMAB	4	3
IXABEPILONE	4	3
PERFLUTREN	4	3
CEMIPLIMAB	4	2
FLUDEOXYGLUCOSE F 18	4	2
INTERFERON ALFA-2B	4	2
MAVORIXAFOR	4	2
NIRAPARIB	4	2
PANITUMUMAB	4	2
PANOBINOSTAT	4	2
RAMUCIRUMAB	4	2
VORINOSTAT	4	2
ALECTINIB	4	1
BORTEZOMIB D-MANNITOL	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 34 predictive associations from 35 curated evidence items; also 53 oncogenic, 40 predisposing, 12 prognostic, 2 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
TSC1 Loss-of-function	MTOR Inhibitor	Sensitivity/Response	CIViC B	EID5837 +1
EPAS1 Overexpression	Pazopanib	Sensitivity/Response	CIViC B	EID1673
HDAC2 Expression	Pazopanib + Abexinostat	Sensitivity/Response	CIViC B	EID7057
HIF1A EXPRESSION	Pazopanib	Sensitivity/Response	CIViC B	EID1674
KDM5C Mutation	Sunitinib + Everolimus	Sensitivity/Response	CIViC B	EID5997
MTOR Gain-of-Function	MTOR Inhibitor	Sensitivity/Response	CIViC B	EID5839
PBRM1 Loss-of-function	Ipilimumab	Sensitivity/Response	CIViC B	EID7301
PBRM1 Loss-of-function	Nivolumab + Pembrolizumab	Sensitivity/Response	CIViC B	EID7536
PBRM1 Loss-of-function	Atezolizumab + Durvalumab	Sensitivity/Response	CIViC B	EID7537
PBRM1 Loss-of-function	Nivolumab	Sensitivity/Response	CIViC B	EID7584
PBRM1 Mutation	Sunitinib + Everolimus	Sensitivity/Response	CIViC B	EID5996
PBRM1 Mutation	CTLA-4 Inhibitor + Anti-PD-L1 Monoclonal Antibody	Sensitivity/Response	CIViC B	EID7247
TSC2 Loss-of-function	MTOR Inhibitor	Sensitivity/Response	CIViC B	EID5838
VHL Mutation	Pazopanib	Sensitivity/Response	CIViC B	EID1672
VHL Mutation	Anti-VEGF Monoclonal Antibody	Sensitivity/Response	CIViC B	EID4832
VHL Mutation	Everolimus	Sensitivity/Response	CIViC B	EID5323
BAP1 Mutation	Everolimus + Sunitinib	Resistance	CIViC B	EID5339
HMOX1 EXPRESSION	Sorafenib + Sunitinib	Resistance	CIViC B	EID829
VHL Loss	Pazopanib	Resistance	CIViC B	EID4829
FLT3 T227M	Sunitinib	Adverse Response	CIViC B	EID1317
BAP1 Q267fs	Niraparib	Sensitivity/Response	CIViC C	EID11199
FLCN c.1285dupC	Everolimus	Sensitivity/Response	CIViC C	EID10137
BRD4 Overexpression	JQ1	Sensitivity/Response	CIViC D	EID2957
CCND1 Amplification	Palbociclib	Sensitivity/Response	CIViC D	EID1560
CDKN2A Loss	Palbociclib	Sensitivity/Response	CIViC D	EID1373
CDKN2B Loss	Palbociclib	Sensitivity/Response	CIViC D	EID1374
MTOR E1799K	Sirolimus	Sensitivity/Response	CIViC D	EID1321
MTOR Q2223K	Temsirolimus	Sensitivity/Response	CIViC D	EID4522
SETD2 Loss	ATR Inhibitor + Anti-PD1 Monoclonal Antibody	Sensitivity/Response	CIViC D	EID12580
SETD2 Loss	Akt Inhibitor MK2206 + TGX221 + PI3Kbeta Inhibitor AZD8186	Sensitivity/Response	CIViC D	EID12581

+4 more predictive associations (showing top 30 by evidence level).