Renal cell carcinoma

disease

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Also known as kidney adenocarcinomaRCCrenal cell adenocarcinomarenal cell carcinoma (disease)

Summary

Renal cell carcinoma (MONDO:0005086) is a cancer (an umbrella term covering 11 Mondo subtypes) caused by variants in BAP1, SDHB, and VHL, with 47 cohort genes (201 GWAS associations across 13 studies; 23 CIViC-evidence somatic drivers; 3,322 ClinVar predisposition records) and 973 clinical trials. The dominant Reactome pathway is Regulation of MITF-M-dependent genes involved in cell cycle and proliferation (4 cohort genes). Molecularly, TSC1 Loss-of-function confers sensitivity to MTOR Inhibitor in Renal Cell Carcinoma (CIViC Level B); 25 further subtype–drug associations are mapped below. Top therapeutic interventions include sunitinib, cabozantinib, and tivozanib.

At a glance

Classification: Cancer
Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
Causal genes: BAP1 (GenCC Strong), SDHB (GenCC Strong), VHL (GenCC Strong)
Umbrella term: 11 Mondo subtypes
Cohort genes: 47
GWAS associations: 201
ClinVar variants: 3,322
Clinical trials: 973
Precision-medicine evidence (CIViC): 26 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	8.35	Europe	Validated
Point prevalence	1-5 / 10 000	42	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	renal cell carcinoma
Mondo ID	MONDO:0005086
EFO	EFO:0000681
MeSH	D002292
Orphanet	217071
DOID	DOID:4450
SNOMED CT	702391001
UMLS	C0007134
MedGen	766
GARD	0013215
MedDRA	10067946
NORD	1657
Anatomy (UBERON)	UBERON:0002113
Is cancer (heuristic)	yes

Also known as: kidney adenocarcinoma · RCC · renal cell adenocarcinoma · renal cell carcinoma · renal cell carcinoma (disease)

Data availability: 3,322 ClinVar variants · 201 GWAS associations (13 studies) · 9 GenCC gene-disease records · 1 HPO phenotype · 294 cell lines · 23 intOGen driver records.

Disease family

An umbrella term covering 11 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

Related subtypes (63): epididymal adenocarcinoma, rete testis adenocarcinoma, seminal vesicle adenocarcinoma, ethmoid sinus adenocarcinoma, lacrimal gland adenocarcinoma, papillary adenocarcinoma, fallopian tube adenocarcinoma, bladder adenocarcinoma, ovarian adenocarcinoma, trabecular adenocarcinoma, middle ear adenocarcinoma, bile duct adenocarcinoma, granular cell carcinoma, small intestine adenocarcinoma, urethra adenocarcinoma, villous adenocarcinoma, thymus gland adenocarcinoma, nasal cavity adenocarcinoma, ureter adenocarcinoma, adenocarcinoma in situ, gastroesophageal junction adenocarcinoma, maxillary sinus adenocarcinoma, mucinous adenocarcinoma, acinar cell carcinoma, adenoid cystic carcinoma, breast adenocarcinoma, clear cell adenocarcinoma, colorectal adenocarcinoma, endometrioid adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, prostate adenocarcinoma, signet ring cell carcinoma, cervical adenocarcinoma, serous adenocarcinoma, endometrium adenocarcinoma, sweat gland carcinoma, cystadenocarcinoma, tubular adenocarcinoma, mesonephric adenocarcinoma, scirrhous adenocarcinoma, pancreatic adenocarcinoma, follicular variant thyroid gland papillary carcinoma, gallbladder adenocarcinoma, hepatoid adenocarcinoma, intestinal type adenocarcinoma, micropapillary serous carcinoma, minor salivary gland adenocarcinoma, poorly differentiated thyroid gland carcinoma, salivary gland basal cell adenocarcinoma, submandibular gland adenocarcinoma, sebaceous adenocarcinoma, hepatocellular carcinoma, parathyroid gland carcinoma, pituitary adenocarcinoma, vaginal adenocarcinoma, Paget disease, diffuse type adenocarcinoma, vulvar adenocarcinoma, thyroid gland adenocarcinoma, gastroesophageal adenocarcinoma, adenoacanthoma

Subtypes (11): 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, nonpapillary renal cell carcinoma, MIT family translocation renal cell carcinoma, acquired cystic disease-associated renal cell carcinoma

Genetics & variants

GWAS landscape

201 GWAS associations across 13 studies. Top hits map to 33 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs4903064	1e-65	DPF3	T	0.83
rs4980785	7e-46	LINC02956 - LINC02953	T	0.87
rs6470588	1e-44	PVT1	A	0.87
rs12814794	3e-41	SSPN-AS1, SSPN	A	0.86
rs10846749	2e-30	SCARB1	C	1.12
rs11263432	2e-30	LINC02953 - LINC02952	T	1.13
rs11125068	4e-30	EPAS1	A	1.12
rs4980572	4e-30	MYEOV - LINC02956	A	0.89
rs12637184	2e-24	ACTRT3	A	0.89
rs55735727	2e-23	ACTRT3 - MYNN	A	1.13
rs179784	2e-22	KCNQ1	A	0.91
rs7105934	5e-22	LINC02956 - LINC02953	?	1.43
rs10792035	2e-21	MYEOV	A	1.1
rs73073561	6e-19	ENTPD3-AS1	T	0.91
rs1990443	1e-18	DPF3	T	1.1
rs3807306	3e-18	IRF5	T	0.92
rs4140952	3e-17	DPF3	A	0.92
rs33925946	1e-16	ZBTB42 - VESTAR	T	0.91
rs718314	2e-16	SSPN-AS1	?	1.18
rs7697932	5e-16	H2AZ1-DT	A	1.09
rs2034327	6e-16	EPAS1	C	0.92
rs7734992	2e-15	TERT	T	0.92
rs8033122	2e-15	ZWILCH	A	1.1
rs11894252	3e-15	EPAS1	?	1.16
rs8042593	3e-15	TIPIN	A	0.92
rs7579899	5e-15	EPAS1	?	1.15
rs762624	6e-15	CDKN1A, DINOL	A	0.92
rs1052067	1e-14	PMF1-BGLAP, PMF1	A	1.09
rs7103831	3e-14	LINC02952 - LINC02747	C	1.08
rs57109480	4e-14	DNAJC16	A	0.92

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004710	Scelo G	2017	10,784	20,406	Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
GCST90838662	Dai H	2026	5,313	96,912	Genetic landscape and functional exploration of kidney cancer predisposition in cross-ancestral populations.
GCST90451675	Dai H	2026	4,692	10,116	Genetic landscape and functional exploration of kidney cancer predisposition in cross-ancestral populations.
GCST000907	Purdue MP	2010	3,772	8,505	Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.
GCST008224	Laskar RS	2019	3,227	4,916	Sex specific associations in genome wide association analysis of renal cell carcinoma.
GCST008226	Laskar RS	2019	3,227	4,916	Sex specific associations in genome wide association analysis of renal cell carcinoma.
GCST002835	Henrion MY	2015	2,215	8,566	Common variation at 1q24.1 (ALDH9A1) is a potential risk factor for renal cancer.
GCST001750	Henrion M	2012	2,215	8,566	Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer.
GCST008225	Laskar RS	2019	1,992	3,095	Sex specific associations in genome wide association analysis of renal cell carcinoma.
GCST002273	Gudmundsson J	2013	1,505	67,725	A common variant at 8q24.21 is associated with renal cell cancer.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	2
Tier 3: regulatory	3
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	50
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	37
intergenic_variant	5
regulatory_region_variant	3
5_prime_UTR_variant	1
non_coding_transcript_exon_variant	1
missense_variant	1
3_prime_UTR_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4903064	14	72812712	T>C	0.289	intron_variant	DPF3	1e-65	Tier 4: intronic/intergenic
rs4980785	11	69419726	C>T	0.435	intron_variant	LINC02956 - LINC02953	7e-46	Tier 4: intronic/intergenic
rs6470588	8	127877125	A>C,G,T	0.464	intron_variant	PVT1	1e-44	Tier 4: intronic/intergenic
rs12814794	12	26287765	G>A	0.338	intron_variant	SSPN-AS1, SSPN	3e-41	Tier 4: intronic/intergenic
rs10846749	12	124833902	G>A,C,T	0.363	intron_variant	SCARB1	2e-30	Tier 4: intronic/intergenic
rs11263432	11	69432586	T>A,C,G	0.407	regulatory_region_variant	LINC02953 - LINC02952	2e-30	Tier 3: regulatory
rs11125068	2	46300677	A>G,T	0.446	intron_variant	EPAS1	4e-30	Tier 4: intronic/intergenic
rs4980572	11	69379851	G>A,C,T	0.436	intergenic_variant	MYEOV - LINC02956	4e-30	Tier 4: intronic/intergenic
rs12637184	3	169769649	G>A	0.306	5_prime_UTR_variant	ACTRT3	2e-24	Tier 2: splice/UTR
rs55735727	3	169770360	A>C,G,T	0.305	intron_variant	ACTRT3 - MYNN	2e-23	Tier 4: intronic/intergenic
rs179784	11	2760594	G>A	0.484	intron_variant	KCNQ1	2e-22	Tier 4: intronic/intergenic
rs7105934	11	69424973	G>A,C,T	0.18	intergenic_variant	LINC02956 - LINC02953	5e-22	Tier 4: intronic/intergenic
rs10792035	11	69306340	A>C,G,T	0.415	intron_variant	MYEOV	2e-21	Tier 4: intronic/intergenic
rs73073561	3	40315807	G>T	0.361	intergenic_variant	ENTPD3-AS1	6e-19	Tier 4: intronic/intergenic
rs1990443	14	72806207	C>T	0.246	intron_variant	DPF3	1e-18	Tier 4: intronic/intergenic
rs3807306	7	128940626	G>A,C,T	0.458	intron_variant	IRF5	3e-18	Tier 4: intronic/intergenic
rs4140952	14	72828118	A>G	0.4	intron_variant	DPF3	3e-17	Tier 4: intronic/intergenic
rs33925946	14	104805499	G>T	0.27	regulatory_region_variant	ZBTB42 - VESTAR	1e-16	Tier 3: regulatory
rs718314	12	26300350	A>C,G,T	0.26	intron_variant	SSPN-AS1	2e-16	Tier 4: intronic/intergenic
rs7697932	4	100084161	A>G,T	0.326	intron_variant	H2AZ1-DT	5e-16	Tier 4: intronic/intergenic
rs2034327	2	46321901	G>C	0.464	intron_variant	EPAS1	6e-16	Tier 4: intronic/intergenic
rs7734992	5	1280013	T>A,C	0.426	intron_variant	TERT	2e-15	Tier 4: intronic/intergenic
rs8033122	15	66528117	T>A,G	0.245	intron_variant	ZWILCH	2e-15	Tier 4: intronic/intergenic
rs11894252	2	46306237	T>A,C,G	0.49	intron_variant	EPAS1	3e-15	Tier 4: intronic/intergenic
rs8042593	15	66338231	G>A,C	0.353	intron_variant	TIPIN	3e-15	Tier 4: intronic/intergenic
rs7579899	2	46310465	A>G,T	0.49	intron_variant	EPAS1	5e-15	Tier 4: intronic/intergenic
rs762624	6	36677811	A>C,G,T	0.333	non_coding_transcript_exon_variant	CDKN1A, DINOL	6e-15	Tier 4: intronic/intergenic
rs1052067	1	156236330	G>A	0.268	missense_variant	PMF1-BGLAP, PMF1	1e-14	Tier 1: coding
rs7103831	11	69449829	C>A,G,T	0.394	regulatory_region_variant	LINC02952 - LINC02747	3e-14	Tier 3: regulatory
rs57109480	1	15585981	G>A	0.347	intergenic_variant	DNAJC16	4e-14	Tier 4: intronic/intergenic

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

332 uncertain significance, 102 likely benign, 91 benign/likely benign, 71 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13881	NM_000245.4(MET):c.3392T>C (p.Met1131Thr)	MET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13883	NM_000245.4(MET):c.3658G>A (p.Val1220Ile)	MET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13887	NM_000245.4(MET):c.3281A>G (p.His1094Arg)	MET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1000490	NM_000245.4(MET):c.2102+5T>G	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007762	NM_000245.4(MET):c.462A>G (p.Ile154Met)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009066	NM_000245.4(MET):c.1477G>A (p.Glu493Lys)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1013952	NM_000245.4(MET):c.625C>T (p.His209Tyr)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1021217	NM_000245.4(MET):c.1483A>C (p.Thr495Pro)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1021858	NM_000245.4(MET):c.3403A>T (p.Ser1135Cys)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1023078	NM_000245.4(MET):c.2806G>T (p.Ala936Ser)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1026935	NM_000245.4(MET):c.1235G>A (p.Arg412His)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1035944	NM_000245.4(MET):c.166A>G (p.Ile56Val)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1036057	NM_000245.4(MET):c.841T>G (p.Phe281Val)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1036459	NM_000245.4(MET):c.914A>G (p.Lys305Arg)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1039810	NM_000245.4(MET):c.2965G>A (p.Val989Ile)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1041854	NM_000245.4(MET):c.1303A>G (p.Ser435Gly)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1051943	NM_000245.4(MET):c.1972G>C (p.Val658Leu)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1053567	NM_000245.4(MET):c.287T>G (p.Phe96Cys)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1055914	NM_000245.4(MET):c.3287C>G (p.Thr1096Ser)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1057320	NM_000245.4(MET):c.4136T>G (p.Val1379Gly)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1109633	NM_000245.4(MET):c.1863-5T>C	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1115115	NM_000245.4(MET):c.255G>A (p.Lys85=)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1131068	NM_000245.4(MET):c.1953A>G (p.Thr651=)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1208570	NM_000245.4(MET):c.3936-13_3936-10del	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1315624	NM_000245.4(MET):c.1490A>G (p.Asn497Ser)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1316166	NM_000245.4(MET):c.2365-11T>A	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1317318	NM_000245.4(MET):c.1890G>T (p.Met630Ile)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1320342	NM_000245.4(MET):c.617T>C (p.Phe206Ser)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1323275	NM_000245.4(MET):c.4068T>A (p.Tyr1356Ter)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
132694	NM_000245.4(MET):c.1039G>A (p.Ala347Thr)	MET	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 117 · Orphanet: 132 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

Gene	HGNC	Evidence routes
TNFRSF10B	TNFRSF10B	GWAS, Orphanet
MYC	MYC	GWAS, Orphanet
ATM	ATM	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SDHB			CIViC #5177
VHL	LoF	CCRCC,PGNG,RCC	CIViC #58
CDKN2B			CIViC #916
EPAS1	Act	PGNG	CIViC #1705
MITF			CIViC #3527
RNF2	LoF	BRCA,CCRCC,CESC,CHOL,ESCA,HCC,PANCREAS,PLMESO,PRCC,RCC,SACA,SKCM,STAD,UM	CIViC #70
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
FLCN	LoF	LUAD	CIViC #19959
PBRM1	LoF	CCRCC,CEAD,CHOL,COADREAD,ESCA,GBC,LUAD,MEL,NSCLC,PLMESO,PRCC,RCC,SKCM,STAD,UCEC	CIViC #62
KLLN			CIViC #32083
FLT3	Act	ALL,AML	CIViC #24
HIF1A	Act	WDTC	CIViC #2596
HMOX1			CIViC #2657
B4GALT1			CIViC #2239
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41
TFE3			CIViC #5734
RBFOX1	LoF	PRAD
PDZD2	LoF	PLMESO
MYC	Act	AML,BL,MLYM,NHL	CIViC #3737
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69

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
BAP1	Strong	Autosomal dominant	renal cell carcinoma	9
MAGI1	Strong	Autosomal dominant	renal cell carcinoma	9
SDHB	Strong	Autosomal dominant	renal cell carcinoma	16
VHL	Strong	Autosomal dominant	renal cell carcinoma	12
CDKN2B	Moderate	Autosomal dominant	renal cell carcinoma	3
MITF	Moderate	Autosomal dominant	renal cell carcinoma	19
PTEN	Moderate	Autosomal dominant	renal cell carcinoma	17
SDHC	Moderate	Autosomal dominant	renal cell carcinoma	11
SDHD	Moderate	Autosomal dominant	renal cell carcinoma	16
TMEM127	Moderate	Autosomal dominant	renal cell carcinoma	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDHB	Orphanet:139411	Carney triad
SDHB	Orphanet:201	Cowden syndrome
SDHB	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
SDHB	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHB	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHB	Orphanet:44890	Gastrointestinal stromal tumor
SDHB	Orphanet:97286	Carney-Stratakis syndrome
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
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
MITF	Orphanet:293822	MITF-related melanoma and renal cell carcinoma predisposition syndrome
MITF	Orphanet:319298	Papillary renal cell carcinoma
MITF	Orphanet:404511	Clear cell papillary renal cell carcinoma
MITF	Orphanet:42665	Tietz syndrome
MITF	Orphanet:618	Familial melanoma
MITF	Orphanet:895	Waardenburg syndrome type 2
MITF	Orphanet:897	Waardenburg-Shah syndrome
RNF2	Orphanet:528084	Non-specific syndromic intellectual disability
SDHC	Orphanet:139411	Carney triad
SDHC	Orphanet:201	Cowden syndrome
SDHC	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHC	Orphanet:44890	Gastrointestinal stromal tumor
SDHC	Orphanet:97286	Carney-Stratakis syndrome
SDHD	Orphanet:100093	Carcinoid syndrome
SDHD	Orphanet:201	Cowden syndrome
SDHD	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
SDHD	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHD	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHD	Orphanet:97286	Carney-Stratakis 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)

Cohort genes → proteins

47 cohort genes, 45 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	19
civic_only	12
multi_evidence	16

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDHB	HGNC:10681	ENSG00000117118	P21912	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	gencc,clinvar
VHL	HGNC:12687	ENSG00000134086	P40337	von Hippel-Lindau disease tumor suppressor	gencc,civic_evidence
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gencc,civic_evidence
EPAS1	HGNC:3374	ENSG00000116016	Q99814	Endothelial PAS domain-containing protein 1	gwas,civic_evidence
MITF	HGNC:7105	ENSG00000187098	O75030	Microphthalmia-associated transcription factor	gencc,clinvar
RNF2	HGNC:10061	ENSG00000121481	Q99496	E3 ubiquitin-protein ligase RING2	civic_evidence
SDHC	HGNC:10682	ENSG00000143252	Q99643	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	gencc
SDHD	HGNC:10683	ENSG00000204370	O14521	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	gencc
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
TMEM127	HGNC:26038	ENSG00000135956	O75204	Transmembrane protein 127	gencc
FLCN	HGNC:27310	ENSG00000154803	Q8NFG4	Folliculin	civic_evidence
PBRM1	HGNC:30064	ENSG00000163939	Q86U86	Protein polybromo-1	civic_evidence
KLLN	HGNC:37212	ENSG00000227268	B2CW77	Killin	civic_evidence
FLT3	HGNC:3765	ENSG00000122025	P36888	Receptor-type tyrosine-protein kinase FLT3	civic_evidence
HIF1A	HGNC:4910	ENSG00000100644	Q16665	Hypoxia-inducible factor 1-alpha	civic_evidence
HMOX1	HGNC:5013	ENSG00000100292	P09601	Heme oxygenase 1	civic_evidence
B4GALT1	HGNC:924	ENSG00000086062	P15291	Beta-1,4-galactosyltransferase 1	civic_evidence
MAGI1	HGNC:946	ENSG00000151276	Q96QZ7	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1	gencc
BAP1	HGNC:950	ENSG00000163930	Q92560	Ubiquitin carboxyl-terminal hydrolase BAP1	gencc
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	gencc
TFE3	HGNC:11752	ENSG00000068323	P19532	Transcription factor E3	clinvar
TNFRSF10B	HGNC:11905	ENSG00000120889	O14763	Tumor necrosis factor receptor superfamily member 10B	gwas
WNT2	HGNC:12780	ENSG00000105989	P09544	Protein Wnt-2	clinvar
ZEB2	HGNC:14881	ENSG00000169554	O60315	Zinc finger E-box-binding homeobox 2	gwas
CAV1	HGNC:1527	ENSG00000105974	Q03135	Caveolin-1	clinvar
SCARB1	HGNC:1664	ENSG00000073060	Q8WTV0	Scavenger receptor class B member 1	gwas
DPF3	HGNC:17427	ENSG00000205683	Q92784	Zinc finger protein DPF3	gwas
RBFOX1	HGNC:18222	ENSG00000078328	Q9NWB1	RNA binding protein fox-1 homolog 1	gwas
PDZD2	HGNC:18486	ENSG00000133401	O15018	PDZ domain-containing protein 2	gwas
RHOBTB2	HGNC:18756	ENSG00000008853	Q9BYZ6	Rho-related BTB domain-containing protein 2	gwas
SAMD5	HGNC:21180	ENSG00000203727	Q5TGI4	Sterile alpha motif domain-containing protein 5	gwas
ABTB3	HGNC:23844	ENSG00000151136	A6QL63	Ankyrin repeat- and BTB/POZ domain-containing protein 3	gwas
STEAP3	HGNC:24592	ENSG00000115107	Q658P3	Metalloreductase STEAP3	gwas
STN1	HGNC:26200	ENSG00000107960	Q9H668	CST complex subunit STN1	gwas
SLC6A18	HGNC:26441	ENSG00000164363	Q96N87	Inactive sodium-dependent neutral amino acid transporter B(0)AT3	gwas
POGLUT3	HGNC:28496	ENSG00000178202	Q7Z4H8	Protein O-glucosyltransferase 3	gwas
LRRIQ4	HGNC:34298	ENSG00000188306	A6NIV6	Leucine-rich repeat and IQ domain-containing protein 4	gwas
FAF1	HGNC:3578	ENSG00000185104	Q9UNN5	FAS-associated factor 1	gwas
COMETT	HGNC:51196	ENSG00000231210		cytosolic oncogenic antisense to MET transcript	clinvar
ITPR2	HGNC:6181	ENSG00000123104	Q14571	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2	gwas
MET	HGNC:7029	ENSG00000105976	P08581	Hepatocyte growth factor receptor	clinvar
MYC	HGNC:7553	ENSG00000136997	P01106	Myc proto-oncogene protein	gwas
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	gwas
PVT1	HGNC:9709	ENSG00000249859		Pvt1 oncogene	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDHB	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
VHL	von Hippel-Lindau disease tumor suppressor	Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
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.
MITF	Microphthalmia-associated transcription factor	Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis.
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.
SDHC	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
SDHD	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
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.
TMEM127	Transmembrane protein 127	Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1.
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).
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.
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.
B4GALT1	Beta-1,4-galactosyltransferase 1	Galactosyltransferase acting in the Golgi stacks.
MAGI1	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1	Plays a role in coupling actin fibers to cell junctions in endothelial cells, via its interaction with AMOTL2 and CDH5.
BAP1	Ubiquitin carboxyl-terminal hydrolase BAP1	Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
TFE3	Transcription factor E3	Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response.
TNFRSF10B	Tumor necrosis factor receptor superfamily member 10B	Receptor for the cytotoxic ligand TNFSF10/TRAIL.
WNT2	Protein Wnt-2	Ligand for members of the frizzled family of seven transmembrane receptors.
ZEB2	Zinc finger E-box-binding homeobox 2	Transcriptional inhibitor that binds to DNA sequence 5’-CACCT-3’ in different promoters.
CAV1	Caveolin-1	May act as a scaffolding protein within caveolar membranes.
SCARB1	Scavenger receptor class B member 1	Receptor for different ligands such as phospholipids, cholesterol ester, lipoproteins, phosphatidylserine and apoptotic cells.
DPF3	Zinc finger protein DPF3	Belongs to the neuron-specific chromatin remodeling complex (nBAF complex).
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
RHOBTB2	Rho-related BTB domain-containing protein 2	Regulator of cell proliferation and apoptosis.
ABTB3	Ankyrin repeat- and BTB/POZ domain-containing protein 3	Cortical and hippocampal inhibitory interneuron-specific protein localized at glutamatergic (excitatory) synapses, where it supports cell type-specific synaptic function.
STEAP3	Metalloreductase STEAP3	Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane.
STN1	CST complex subunit STN1	Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex.
SLC6A18	Inactive sodium-dependent neutral amino acid transporter B(0)AT3	Does not show neutral amino acid transporter activity.
POGLUT3	Protein O-glucosyltransferase 3	Protein glucosyltransferase that catalyzes the transfer of glucose from UDP-glucose to a serine residue within the consensus sequence peptide C-X-N-T-X-G-S-F-X-C.
FAF1	FAS-associated factor 1	Ubiquitin-binding protein.
ITPR2	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2	Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm.
MET	Hepatocyte growth factor receptor	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.
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’.
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.

Protein-family classification

Druggable: 13 · Difficult: 14 · Unknown: 20 · Druggable fraction: 0.28

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	4	2.4×	0.399
Scaffold/PPI	6	2.2×	0.399
Transcription factor	8	1.4×	0.610
Ion channel	1	2.4×	0.638
Enzyme (other)	5	1.3×	0.638
Phosphatase	1	1.8×	0.647
Protease	1	0.8×	0.907
Antibody/Immunoglobulin	1	0.6×	0.907
Other/Unknown	20	0.8×	0.976

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDHB	Enzyme (other)	yes	1.3.5.1	2Fe-2S_ferredoxin-type, Succ_DH/fum_Rdtase_Fe-S, 2Fe2S_fd_BS
VHL	Enzyme (other)	yes	2.3.2.B13	VHL_tumour_suppress_b/a_dom, VHL_alpha_dom, VHL_beta_dom
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
EPAS1	Transcription factor	no		PAS, Nuc_translocat, PAC
MITF	Transcription factor	no		bHLH_dom, MiT/TFE_C, MiT/TFE_N
RNF2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
SDHC	Enzyme (other)	yes	1.3.5.1	SuccDH_FuR_B_TM-su, Succ_DH_cytb556, Succ_DH_cyt_bsu_CS
SDHD	Other/Unknown	no		CybS, SQR/QFR_C/D
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
TMEM127	Other/Unknown	no		TMEM127, TMEM127_TM
FLCN	Other/Unknown	no		Folliculin, Folliculin_DENN, Folliculin/SMCR8_longin
PBRM1	Other/Unknown	no		BAH_dom, Bromodomain, HMG_box_dom
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
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
B4GALT1	Enzyme (other)	yes	2.4.1.133	Galactosyl_T, Galactosyl_T_C, Galactosyl_T_N
MAGI1	Kinase	yes		WW_dom, PDZ, Guanylate_kin-like_dom
BAP1	Protease	yes	3.4.19.12	Peptidase_C12_UCH, Peptidase_C12_UCH_sf, Papain-like_cys_pep_sf
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
TFE3	Transcription factor	no		bHLH_dom, MiT/TFE_C, bHLHzip_TFE3
TNFRSF10B	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
WNT2	Other/Unknown	no		Wnt, Wnt2, Wnt_CS
ZEB2	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
CAV1	Other/Unknown	no		Caveolin, Caveolin_CS
SCARB1	Other/Unknown	no		CD36_fam, CD36/SCARB1/SNMP1
DPF3	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
RBFOX1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
PDZD2	Scaffold/PPI	no		PDZ, PDZ_sf
RHOBTB2	Other/Unknown	no		BTB/POZ_dom, Small_GTPase, Small_GTPase_Rho
SAMD5	Scaffold/PPI	no		SAM, SAM/pointed_sf, SAM-SH3_domain_protein
ABTB3	Scaffold/PPI	no		BTB/POZ_dom, Ankyrin_rpt, Histone-fold
STEAP3	Other/Unknown	no		Fe3_Rdtase_TM_dom, P5C_Rdtase_cat_N, NAD(P)-bd_dom_sf
STN1	Other/Unknown	no		NA-bd_OB_tRNA, NA-bd_OB-fold, Stn1
SLC6A18	Other/Unknown	no		Na/ntran_symport, Neutral_aa_SLC6, SNS_sf
POGLUT3	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, CAP10, Ig-like_fold
LRRIQ4	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf
FAF1	Other/Unknown	no		UBX_dom, UAS, Ubiquitin-like_domsf
COMETT	Other/Unknown	no
ITPR2	Ion channel	yes		InsP3_rcpt, RIH_dom, Ion_trans_dom
MET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Semap_dom
MYC	Transcription factor	no		Tscrpt_reg_Myc, Myc-LZ, bHLH_dom
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
PVT1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

45 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)	46
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	5
calcaneal tendon	5
monocyte	4
lower esophagus mucosa	4
male germ line stem cell (sensu Vertebrata) in testis	4
lower lobe of lung	3
stromal cell of endometrium	3
upper arm skin	3
colonic epithelium	3
cartilage tissue	3
left testis	3
jejunal mucosa	2
pigmented layer of retina	2
ganglionic eminence	2
primordial germ cell in gonad	2
right adrenal gland	2
right adrenal gland cortex	2
rectum	2
Brodmann (1909) area 23	2
blood	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDHB	293	ubiquitous	marker	heart left ventricle, cardiac ventricle, apex of heart
VHL	186	ubiquitous	marker	cortical plate, monocyte, mononuclear cell
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
EPAS1	298	ubiquitous	marker	right lung, lower lobe of lung, adult organism
MITF	293	ubiquitous	marker	pigmented layer of retina, retina, skeletal muscle tissue of biceps brachii
RNF2	178	ubiquitous	marker	primordial germ cell in gonad, cortical plate, ganglionic eminence
SDHC	134	ubiquitous	marker	islet of Langerhans, right adrenal gland cortex, right adrenal gland
SDHD	287	ubiquitous	marker	jejunal mucosa, rectum, jejunum
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
TMEM127	284	ubiquitous	marker	leukocyte, monocyte, blood
FLCN	261	ubiquitous	marker	buccal mucosa cell, right hemisphere of cerebellum, cerebellar hemisphere
PBRM1	289	ubiquitous	marker	cortical plate, ganglionic eminence, amniotic fluid
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
HIF1A	295	ubiquitous	marker	pancreatic ductal cell, epithelial cell of pancreas, corpus epididymis
HMOX1	230	ubiquitous	marker	cartilage tissue, spleen, monocyte
B4GALT1	276	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, left uterine tube
MAGI1	133	ubiquitous	marker	ventricular zone, sural nerve, corpus callosum
BAP1	253	ubiquitous	marker	left testis, right testis, right frontal lobe
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
TFE3	292	ubiquitous	marker	inferior olivary complex, dorsal motor nucleus of vagus nerve, olfactory bulb
TNFRSF10B	289	ubiquitous	marker	cartilage tissue, mucosa of urinary bladder, blood
WNT2	154	broad	marker	stromal cell of endometrium, placenta, lower lobe of lung
ZEB2	290	ubiquitous	marker	cortical plate, sural nerve, monocyte
CAV1	287	ubiquitous	marker	parietal pleura, lower lobe of lung, pleura
SCARB1	244	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
DPF3	217	ubiquitous	marker	left ventricle myocardium, quadriceps femoris, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 41.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYC	20,608
PTEN	11,626
HIF1A	9,734
CDKN2A	9,311
CCND1	8,328
FBXW7	7,956
ATM	7,383
CAV1	6,673
MET	5,823
SCARB1	5,484

Intra-cohort edges

A	B	Sources
ATM	HIF1A	biogrid_interaction
B4GALT1	TSC1	biogrid_interaction
BAP1	PBRM1	string_interaction
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	CDKN2B	string_interaction
CCND1	MYC	string_interaction
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	HIF1A	string_interaction
CDKN2A	MYC	string_interaction
DPF3	PBRM1	biogrid_interaction, string_interaction
EPAS1	HIF1A	string_interaction
EPAS1	MYC	string_interaction
EPAS1	TMEM127	string_interaction
EPAS1	VHL	biogrid_interaction, intact, string_interaction
FBXW7	MITF	intact
FBXW7	MYC	biogrid_interaction, intact, string_interaction
FBXW7	PTEN	string_interaction
FBXW7	SDHD	intact
FBXW7	ZEB2	biogrid_interaction
FLCN	KLLN	string_interaction
FLCN	TFE3	string_interaction
FLT3	VHL	biogrid_interaction
HIF1A	MYC	string_interaction
HIF1A	VHL	biogrid_interaction, intact, string_interaction
KLLN	PTEN	string_interaction
KLLN	SDHB	string_interaction
KLLN	SDHD	string_interaction
MET	PTEN	biogrid_interaction
MITF	TFE3	biogrid_interaction, intact, string_interaction
PBRM1	VHL	biogrid_interaction
PDZD2	PTEN	intact
PTEN	SDHD	intact
PTEN	TSC1	string_interaction
RHOBTB2	TNFRSF10B	string_interaction
SDHB	SDHC	string_interaction
SDHB	SDHD	biogrid_interaction, string_interaction
SDHB	TMEM127	string_interaction
SDHC	SDHD	biogrid_interaction, intact, string_interaction
SDHC	TMEM127	string_interaction
SDHD	TMEM127	string_interaction
TSC1	VHL	biogrid_interaction

Structural data

PDB: 32 · AlphaFold-only: 13 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VHL	P40337	142
MET	P08581	130
EPAS1	Q99814	43
PBRM1	Q86U86	30
HMOX1	P09601	26
HIF1A	Q16665	25
MYC	P01106	25
B4GALT1	P15291	19
MAGI1	Q96QZ7	16
FAF1	Q9UNN5	16
RNF2	Q99496	15
ATM	Q13315	14
TNFRSF10B	O14763	13
MITF	O75030	12
PTEN	P60484	12
CCND1	P24385	11
FLT3	P36888	11
DPF3	Q92784	8
STN1	Q9H668	8
FBXW7	Q969H0	7
SDHB	P21912	6
TSC1	Q92574	5
CDKN2A	P42771	5
FLCN	Q8NFG4	4
BAP1	Q92560	4
RBFOX1	Q9NWB1	4
SDHC	Q99643	2
SDHD	O14521	2
STEAP3	Q658P3	2
TFE3	P19532	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POGLUT3	Q7Z4H8	93.16
SLC6A18	Q96N87	90.62
CDKN2B	P42772	90.12
LRRIQ4	A6NIV6	90.00
WNT2	P09544	88.89
SCARB1	Q8WTV0	84.25
RHOBTB2	Q9BYZ6	81.89
TMEM127	O75204	77.38
ABTB3	A6QL63	73.18
SAMD5	Q5TGI4	71.96
KLLN	B2CW77	51.20
PDZD2	O15018
ITPR2	Q14571

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 422. Enrichment computed across 47 evidence-associated genes (36 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 36 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	4	63.4×	2e-04	MITF, CCND1, CDKN2A, MET
MITF-M-regulated melanocyte development	5	15.9×	0.003	MITF, TFE3, CCND1, CDKN2A, MET
Maturation of TCA enzymes and regulation of TCA cycle	3	47.6×	0.004	SDHB, SDHC, SDHD
Mitotic G1 phase and G1/S transition	4	20.5×	0.004	CDKN2B, CCND1, CDKN2A, MYC
Citric acid cycle (TCA cycle)	3	35.2×	0.007	SDHB, SDHC, SDHD
G1 Phase	3	32.8×	0.007	CDKN2B, CCND1, CDKN2A
PTK6 Expression	2	105.7×	0.008	EPAS1, HIF1A
RNA Polymerase II Transcription	8	5.0×	0.008	CDKN2B, CAV1, CCND1, CDKN2A, STEAP3, MET, MYC, ATM
RUNX3 regulates WNT signaling	2	63.4×	0.013	CCND1, MYC
RUNX3 regulates p14-ARF	2	63.4×	0.013	CCND1, CDKN2A
Transcriptional regulation by RUNX3	3	22.7×	0.013	CCND1, CDKN2A, MYC
NOTCH1 Intracellular Domain Regulates Transcription	3	19.8×	0.013	FBXW7, HIF1A, MYC
Cyclin D associated events in G1	3	19.4×	0.013	CDKN2B, CCND1, CDKN2A
Interleukin-4 and Interleukin-13 signaling	4	11.4×	0.013	CCND1, HIF1A, HMOX1, MYC
Cell Cycle	6	6.0×	0.013	CDKN2B, CCND1, CDKN2A, STN1, MYC, ATM
Regulation of gene expression by Hypoxia-inducible Factor	2	52.9×	0.016	EPAS1, HIF1A
Pexophagy	2	52.9×	0.016	EPAS1, ATM
Gene expression (Transcription)	8	4.0×	0.016	CDKN2B, CAV1, CCND1, CDKN2A, STEAP3, MET, MYC, ATM
Cellular response to hypoxia	2	48.8×	0.016	EPAS1, HIF1A
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	3	16.4×	0.017	VHL, EPAS1, HIF1A
Stabilization of p53	2	42.3×	0.019	CDKN2A, ATM
p53-Dependent G1 DNA Damage Response	2	39.6×	0.019	CDKN2A, ATM
p53-Dependent G1/S DNA damage checkpoint	2	39.6×	0.019	CDKN2A, ATM
MITF-M-dependent gene expression	3	15.1×	0.019	CCND1, CDKN2A, MET
Signaling by NOTCH	3	14.6×	0.019	CCND1, MYC, B4GALT1
Disease	9	3.3×	0.020	CAV1, CCND1, CDKN2A, SLC6A18, ITPR2, MET, MYC, ATM (+1 more)
G1/S DNA Damage Checkpoints	2	37.3×	0.020	CDKN2A, ATM
Defective B4GALT1 causes CDG-2d	1	317.2×	0.024	B4GALT1
R-HSA-5619079	1	317.2×	0.024	SLC6A18
R-HSA-5659729	1	317.2×	0.024	SLC6A18

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 44 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial electron transport, succinate to ubiquinone	3	229.8×	1e-04	SDHB, SDHC, SDHD
negative regulation of TOR signaling	4	51.1×	3e-04	TSC1, TMEM127, FLCN, HIF1A
endothelial cell proliferation	4	49.4×	3e-04	ZEB2, CAV1, SCARB1, HMOX1
cellular response to hypoxia	6	16.5×	3e-04	VHL, EPAS1, SDHD, CCND1, HIF1A, MYC
protein stabilization	7	10.6×	5e-04	VHL, TSC1, FBXW7, CDKN2A, ABTB3, ATM, PTEN
negative regulation of cell population proliferation	8	7.7×	1e-03	VHL, CDKN2B, TSC1, CDKN2A, TMEM127, PBRM1, BAP1, PTEN
regulation of G1/S transition of mitotic cell cycle	4	27.9×	0.001	CDKN2B, DPF3, CDKN2A, PBRM1
regulation of G0 to G1 transition	3	46.0×	0.003	CDKN2B, DPF3, PBRM1
positive regulation of transforming growth factor beta receptor signaling pathway	3	35.9×	0.006	CDKN2B, ZEB2, FLCN
tricarboxylic acid cycle	3	34.8×	0.006	SDHB, SDHC, SDHD
positive regulation of apoptotic process	6	7.7×	0.007	TNFRSF10B, CDKN2A, FLCN, FAF1, ATM, B4GALT1
positive regulation of transcription by RNA polymerase II	11	3.7×	0.007	EPAS1, MITF, TFE3, WNT2, ZEB2, CDKN2A, HIF1A, MET (+3 more)
lactation	3	28.7×	0.009	CAV1, CCND1, HIF1A
common myeloid progenitor cell proliferation	2	85.1×	0.011	FLT3, BAP1
iris morphogenesis	2	85.1×	0.011	WNT2, HIF1A
negative regulation of cell size	2	76.6×	0.012	TSC1, PTEN
intracellular oxygen homeostasis	2	69.6×	0.012	EPAS1, HIF1A
mammary gland epithelial cell proliferation	2	69.6×	0.012	CCND1, CDKN2A
regulation of osteoclast differentiation	2	69.6×	0.012	MITF, TFE3
positive regulation of double-strand break repair	3	23.4×	0.012	DPF3, PBRM1, ATM
negative regulation of TORC1 signaling	3	22.1×	0.012	VHL, TSC1, ATM
cellular senescence	3	20.2×	0.015	CDKN2B, CDKN2A, ATM
negative regulation of epithelial cell proliferation	3	19.8×	0.015	CDKN2B, FLCN, B4GALT1
negative regulation of epithelial cell differentiation	2	54.7×	0.017	CAV1, CCND1
positive regulation of cell differentiation	3	18.2×	0.017	VHL, DPF3, PBRM1
proton motive force-driven mitochondrial ATP synthesis	3	17.9×	0.017	SDHB, SDHC, SDHD
negative regulation of macroautophagy	2	51.1×	0.018	TSC1, HMOX1
negative regulation of transcription by RNA polymerase II	9	3.6×	0.018	VHL, MITF, RNF2, ZEB2, CAV1, CCND1, CDKN2A, FLCN (+1 more)
endothelial cell morphogenesis	2	47.9×	0.019	MET, MAGI1
intracellular iron ion homeostasis	3	16.6×	0.019	HIF1A, HMOX1, MYC

Therapeutics

Drugs indicated for this disease

10 approved, 25 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Axitinib	Approved (phase 4)
Belzutifan	Approved (phase 4)
Bevacizumab	Approved (phase 4)
Everolimus	Approved (phase 4)
Ipilimumab	Approved (phase 4)
Medroxyprogesterone Acetate	Approved (phase 4)
Nivolumab	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Sunitinib	Approved (phase 4)
Temsirolimus	Approved (phase 4)
Abexinostat	Phase 3 (in late-stage trials)
Aldesleukin	Phase 3 (in late-stage trials)
Atezolizumab	Phase 3 (in late-stage trials)
Avelumab	Phase 3 (in late-stage trials)
Bempegaldesleukin	Phase 3 (in late-stage trials)
CM-082	Phase 3 (in late-stage trials)
Cabozantinib	Phase 3 (in late-stage trials)
Capecitabine	Phase 3 (in late-stage trials)
Denosumab	Phase 3 (in late-stage trials)
Dovitinib	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Epacadostat	Phase 3 (in late-stage trials)
Girentuximab	Phase 3 (in late-stage trials)
INTERFERON ALFA-2A	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Lenvatinib	Phase 3 (in late-stage trials)
Pazopanib	Phase 3 (in late-stage trials)
Quavonlimab	Phase 3 (in late-stage trials)
Rocapuldencel-T	Phase 3 (in late-stage trials)
Savolitinib	Phase 3 (in late-stage trials)
Sorafenib	Phase 3 (in late-stage trials)
Tivozanib	Phase 3 (in late-stage trials)
Tremelimumab	Phase 3 (in late-stage trials)
Vitespen	Phase 3 (in late-stage trials)
Zanzalintinib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aflibercept, Atorvastatin, Balstilimab, Botensilimab, Brivanib Alaninate, Cadonilimab, Camrelizumab, Carboxyamidotriazole, Carotuximab, Catequentinib, Cediranib, Celecoxib, Cisplatin, Dalantercept, Decitabine, Dexamethasone, Diphenhydramine, Doxorubicin, Entinostat, Enzastaurin, Famitinib, Filgrastim, Fludarabine, Fluzoparib, Fruquintinib, Gemcitabine, INTERFERON ALFA-2B, Incomplete Freund’S Adjuvant, Interferon, Ivuxolimab, Ixabepilone, Linifanib, Melphalan, Motexafin Gadolinium, Nintedanib, Oblimersen Sodium, Olaparib, Oxaliplatin, Palbociclib, Panitumumab, Panobinostat, Pegfilgrastim, Pemetrexed, Perifosine, Propranolol, Quinacrine, Ramucirumab, Ranitidine, Regorafenib, Regramostim, Relatlimab, Rilotumumab, Rivoceranib, Sargramostim, Semaxanib, Serplulimab, Sintilimab, Sirolimus, Sitravatinib, Sulfur Hexafluoride, Talazoparib, Testosterone Undecanoate, Thalidomide, Tislelizumab, Toripalimab, Trebananib, Vinblastine, Vorinostat, Zoledronic Acid Anhydrous.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 9 · Phased (≥1): 11 · Undrugged: 36

Druggability breadth: 25 of 47 evidence-associated genes (53%) 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
EPAS1	BELZUTIFAN
MITF	PERHEXILINE MALEATE
CCND1	PALBOCICLIB
FLT3	PONATINIB
HIF1A	EMETINE
MET	AFATINIB
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HIF1A	255	4
FLT3	143	4
MET	95	4
CCND1	35	4
ATM	35	4
VHL	7	4
EPAS1	7	4
MITF	3	4
MYC	3	3
PBRM1	2	2

Drugs targeting cohort genes (top 30)

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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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
MET	2,015	Binding:2005, Functional:6, ADMET:4
CCND1	576	Binding:574, Functional:1, ADMET:1
HIF1A	427	Binding:411, Functional:16
EPAS1	241	Binding:233, Functional:8
ATM	240	Binding:233, Functional:5, ADMET:2
MYC	202	Binding:202
PBRM1	193	Binding:193
HMOX1	23	Binding:22, ADMET:1
RNF2	16	Binding:16
MITF	10	Functional:10
B4GALT1	9	Binding:9
TNFRSF10B	9	Binding:9
PTEN	8	Binding:8
ITPR2	8	Binding:7, Functional:1
BAP1	5	Binding:4, Functional:1
CAV1	5	Binding:5
SDHB	4	Binding:4
MAGI1	4	Binding:4
SCARB1	4	Binding:4
TFE3	3	Binding:3
CDKN2A	2	Binding:2
WNT2	2	Binding:2
FAF1	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SDHB	1.3.5.1	succinate dehydrogenase
VHL	2.3.2.B13
RNF2	2.3.2.27	RING-type E3 ubiquitin transferase
SDHC	1.3.5.1	succinate dehydrogenase
FLT3	2.7.10.1	receptor protein-tyrosine kinase
HMOX1	1.14.14.18	heme oxygenase (biliverdin-producing)
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
BAP1	3.4.19.12	ubiquitinyl hydrolase 1
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
MET	2.7.10.1	receptor protein-tyrosine kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
VHL	3,575
EPAS1	241
CCND1	576
PBRM1	193
FLT3	3,132
HIF1A	427
MET	2,015
MYC	202
ATM	240

Pharmacogenomics

Cohort genes with a PharmGKB record: 46; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

24 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, MET, VHL
CRIZOTINIB	4	FLT3, MET, VHL
EMETINE	4	EPAS1, HIF1A
DOXORUBICIN	4	EPAS1, HIF1A
TOPOTECAN	4	EPAS1, HIF1A
PERHEXILINE MALEATE	4	MITF
PALBOCICLIB	4	CCND1, FLT3, MET
ABEMACICLIB	4	CCND1, FLT3
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
PONATINIB	4	FLT3
AFATINIB	4	FLT3, MET
FEDRATINIB	4	FLT3, MET
NERATINIB	4	FLT3, MET
INFIGRATINIB PHOSPHATE	4	FLT3, MET
INFIGRATINIB	4	FLT3, MET
IBRUTINIB	4	FLT3
REGORAFENIB	4	FLT3
ENTRECTINIB	4	FLT3, MET
PACRITINIB	4	FLT3
FOSTAMATINIB	4	FLT3
QUIZARTINIB DIHYDROCHLORIDE	4	FLT3
CERITINIB	4	FLT3, MET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	VHL, EPAS1, MITF, CCND1, FLT3, HIF1A, MET, ATM
B	Phased (≥1) drug, not yet approved	3	PBRM1, SCARB1, MYC
C	Druggable family + PDB, no drug	7	SDHB, SDHC, HMOX1, B4GALT1, MAGI1, BAP1, PTEN
D	Druggable family + AlphaFold only, no drug	2	POGLUT3, ITPR2
E	Difficult family or no structure, no drug	27	CDKN2B, RNF2, SDHD, TSC1, FBXW7, CDKN2A, TMEM127, FLCN, KLLN, TFE3 (+17 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TFE3	3	MITF
SDHB	4	—
CDKN2B	0	—
RNF2	16	—
SDHC	0	—
SDHD	0	—
TSC1	0	—
FBXW7	0	—
CDKN2A	2	—
TMEM127	0	—
FLCN	0	—
KLLN	0	—
HMOX1	23	—
B4GALT1	9	—
MAGI1	4	—
BAP1	5	—
PTEN	8	—
TNFRSF10B	9	—
WNT2	2	—
ZEB2	0	—
CAV1	5	—
DPF3	0	—
RBFOX1	0	—
PDZD2	0	—
RHOBTB2	0	—
SAMD5	0	—
ABTB3	0	—
STEAP3	0	—
STN1	0	—
SLC6A18	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 973.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	307
PHASE2	273
PHASE1	204
PHASE1/PHASE2	102
PHASE3	56
EARLY_PHASE1	13
PHASE4	12
PHASE2/PHASE3	6

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
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)
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
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)
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)
NCT00033904	PHASE3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	PHASE3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	PHASE3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	PHASE3	COMPLETED	RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
NCT00420888	PHASE2/PHASE3	COMPLETED	ABR-217620/Naptumomab Estafenatox With Interferon-alpha (IFN-alpha) Compared to IFN-alpha Alone in Patients With Advanced Renal Cell Carcinoma
NCT00474786	PHASE3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SUNITINIB	4	28
CABOZANTINIB	4	22
TIVOZANIB	4	19
AXITINIB	4	16
PAZOPANIB	4	16
SORAFENIB	4	14
ALDESLEUKIN	4	11
NIVOLUMAB	4	9
BELZUTIFAN	4	8
TEMSIROLIMUS	4	7
EVEROLIMUS	4	5
IPILIMUMAB	4	5
LENVATINIB	4	4
PEMBROLIZUMAB	4	4
ATEZOLIZUMAB	4	3
AVELUMAB	4	3
PERFLUTREN	4	3
ERIBULIN	4	2
INTERFERON ALFA-2B	4	2
IXABEPILONE	4	2
PANITUMUMAB	4	2
RAMUCIRUMAB	4	2
RELATLIMAB	4	2
RETIFANLIMAB	4	2
ADAGRASIB	4	1
ALECTINIB	4	1
BORTEZOMIB D-MANNITOL	4	1
CAPMATINIB	4	1
CEMIPLIMAB	4	1
COSIBELIMAB	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 26 predictive associations from 27 curated evidence items; also 40 predisposing, 4 prognostic, 3 oncogenic, 1 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
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
FLCN c.1285dupC	Everolimus	Sensitivity/Response	CIViC C	EID10137
CCND1 Amplification	Palbociclib	Sensitivity/Response	CIViC D	EID1560
CDKN2A Loss	Palbociclib	Sensitivity/Response	CIViC D	EID1373
CDKN2B Loss	Palbociclib	Sensitivity/Response	CIViC D	EID1374
VHL Loss-of-function	Temsirolimus	Sensitivity/Response	CIViC D	EID4828
EML4::ALK e2::e20		Sensitivity/Response	CIViC E	EID1266
FBXW7 Loss-of-function	Everolimus	Sensitivity/Response	CIViC E	EID1628

Cohort genes: SDHB, VHL, CDKN2B, EPAS1, MITF, RNF2, TSC1, CCND1, FBXW7, CDKN2A, FLCN, PBRM1, KLLN, FLT3, HIF1A, HMOX1, B4GALT1, PTEN, TFE3, RBFOX1, PDZD2, MYC, ATM, SDHC, SDHD, TMEM127, MAGI1, BAP1, TNFRSF10B, WNT2, ZEB2, CAV1, SCARB1, DPF3, RHOBTB2, SAMD5, ABTB3, STEAP3, STN1, SLC6A18, POGLUT3, LRRIQ4, FAF1, COMETT, ITPR2, MET, PVT1
Drugs: Sunitinib, Cabozantinib, Tivozanib, Axitinib, Pazopanib, Sorafenib, Aldesleukin, Nivolumab, Belzutifan, Temsirolimus, Everolimus, Ipilimumab, Lenvatinib, Pembrolizumab, Atezolizumab, Avelumab, Perflutren, Eribulin, INTERFERON ALFA-2B, Ixabepilone, Panitumumab, Ramucirumab, Relatlimab, Retifanlimab, Adagrasib, Alectinib, Bortezomib D-Mannitol, Capmatinib, Cemiplimab, Cosibelimab, Palbociclib