von Hippel-Lindau disease

Summary

von Hippel-Lindau disease (MONDO:0008667) is a disease caused by VHL (GenCC Definitive), with 11 cohort genes and 45 clinical trials. Molecularly, EPAS1 Overexpression confers sensitivity to Belzutifan in Von Hippel-Lindau Disease (CIViC Level B); 1 further subtype–drug associations are mapped below. Top therapeutic interventions include belzutifan, sunitinib, and cabozantinib.

At a glance

• Prevalence: 1-9 / 100 000 (United Kingdom) [Orphanet-validated]
• Causal gene: VHL (GenCC Definitive)
• Cohort genes: 11
• ClinVar variants: 1,919
• Phenotypes (HPO): 41
• Clinical trials: 45
• Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.1	United Kingdom	Validated
Point prevalence	1-9 / 100 000	2.13	Denmark	Validated
Prevalence at birth	1-9 / 100 000	2.3	United Kingdom	Validated
Prevalence at birth	1-9 / 100 000	3.66	Denmark	Validated
Point prevalence	1-9 / 100 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

41 HPO clinical features (Orphanet curated; top 41 by frequency):

HPO ID	Term	Frequency
HP:0000478	Abnormality of the eye	Very frequent (80-99%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0005584	Renal cell carcinoma	Frequent (30-79%)
HP:0006748	Adrenal pheochromocytoma	Frequent (30-79%)
HP:0006880	Cerebellar hemangioblastoma	Frequent (30-79%)
HP:0009711	Retinal capillary hemangioma	Frequent (30-79%)
HP:0011976	Elevated urinary catecholamines	Frequent (30-79%)
HP:0000572	Visual loss	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0000975	Hyperhidrosis	Occasional (5-29%)
HP:0000980	Pallor	Occasional (5-29%)
HP:0001085	Papilledema	Occasional (5-29%)
HP:0001095	Hypertensive retinopathy	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0001737	Pancreatic cysts	Occasional (5-29%)
HP:0001962	Palpitations	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002321	Vertigo	Occasional (5-29%)
HP:0003334	Elevated circulating catecholamine level	Occasional (5-29%)
HP:0003418	Back pain	Occasional (5-29%)
HP:0003484	Upper limb muscle weakness	Occasional (5-29%)
HP:0005162	Abnormal left ventricular function	Occasional (5-29%)
HP:0005562	Multiple renal cysts	Occasional (5-29%)
HP:0008261	Pancreatic islet cell adenoma	Occasional (5-29%)
HP:0009053	Distal lower limb muscle weakness	Occasional (5-29%)
HP:0009715	Papillary cystadenoma of the epididymis	Occasional (5-29%)
HP:0009763	Limb pain	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0030393	Endolymphatic sac tumor	Occasional (5-29%)
HP:0030405	Pancreatic endocrine tumor	Occasional (5-29%)
HP:0040049	Macular edema	Occasional (5-29%)
HP:0000541	Retinal detachment	Very rare (<1-4%)
HP:0001658	Myocardial infarction	Very rare (<1-4%)
HP:0001901	Polycythemia	Very rare (<1-4%)
HP:0002516	Increased intracranial pressure	Very rare (<1-4%)
HP:0002668	Paraganglioma	Very rare (<1-4%)
HP:0002894	Neoplasm of the pancreas	Very rare (<1-4%)
HP:0012819	Myocarditis	Very rare (<1-4%)
HP:0030424	Epididymal cyst	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	von Hippel-Lindau disease
Mondo ID	MONDO:0008667
MeSH	D006623
OMIM	193300
Orphanet	892
DOID	DOID:14175
ICD-11	1985408165
NCIT	C3105
SNOMED CT	46659004
UMLS	C0019562
MedGen	42458
GARD	0007855
MedDRA	10047716
NORD	1830
Is cancer (heuristic)	no

Also known as: cerebroretinal angiomatosis · familial cerebelloretinal angiomatosis · Lindau disease · VHL · VHL syndrome · VHL-related von Hippel-Lindau disease · Von Hippel Lindau disease · von Hippel-Lindau disease · Von Hippel-Lindau syndrome · von Hippel-Lindau syndrome · Von Hippel-Lindau syndrome (VHL) · von Hippel-Lindau syndrome, modifier of

Data availability: 1,919 ClinVar variants · 31 ClinGen variant curations · 6 GenCC gene-disease records · 45 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › von Hippel-Lindau disease

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

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

600 retrieved; paginated sample, class counts are floors:

302 uncertain significance, 110 likely benign, 69 conflicting classifications of pathogenicity, 44 pathogenic, 44 benign/likely benign, 12 likely pathogenic, 11 pathogenic/likely pathogenic, 8 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068736	NC_000003.11:g.10094065-?_10191654+?del	FANCD2	Pathogenic	criteria provided, single submitter
1070024	NC_000003.11:g.10106407-?_10191654+?del	FANCD2	Pathogenic	criteria provided, single submitter
1069709	NM_000551.4(VHL):c.400G>T (p.Glu134Ter)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
1070973	NM_000551.4(VHL):c.504_519del (p.Ser168fs)	LOC107303340	Pathogenic	criteria provided, single submitter
1177419	NM_000551.4(VHL):c.363del (p.Asp121fs)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
1208816	NM_000551.4(VHL):c.383T>C (p.Leu128Pro)	LOC107303340	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127829	NM_000551.4(VHL):c.445G>T (p.Ala149Ser)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
1451803	NM_000551.4(VHL):c.475A>T (p.Lys159Ter)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
1457709	NM_000551.4(VHL):c.463+1G>T	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
1457988	NM_000551.4(VHL):c.341-11T>A	LOC107303340	Pathogenic	criteria provided, single submitter
167827	NM_000551.4(VHL):c.351G>T (p.Trp117Cys)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
1698896	NM_000551.4(VHL):c.575del (p.Pro192fs)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
1737544	NM_000551.4(VHL):c.406T>G (p.Phe136Val)	LOC107303340	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
177805	NM_000551.3(VHL):c.(?_464)_642+?del	LOC107303340	Pathogenic	no assertion criteria provided
182959	NM_000551.4(VHL):c.477del (p.Glu160fs)	LOC107303340	Pathogenic	reviewed by expert panel
182974	NM_000551.4(VHL):c.525C>G (p.Tyr175Ter)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
182980	NM_000551.4(VHL):c.473T>C (p.Leu158Pro)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
182983	NM_000551.4(VHL):c.482G>A (p.Arg161Gln)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
195093	NM_000551.4(VHL):c.449del (p.Asn150fs)	LOC107303340	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
196284	NM_000551.4(VHL):c.586A>T (p.Lys196Ter)	LOC107303340	Pathogenic	reviewed by expert panel
2034796	NM_000551.4(VHL):c.341-2A>T	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
2087924	NM_000551.4(VHL):c.349T>C (p.Trp117Arg)	LOC107303340	Pathogenic	criteria provided, single submitter
2119727	NM_000551.4(VHL):c.524dup (p.Tyr175Ter)	LOC107303340	Pathogenic	criteria provided, multiple submitters, no conflicts
2203306	NM_000551.4(VHL):c.361G>A (p.Asp121Asn)	LOC107303340	Pathogenic	criteria provided, single submitter
12778	NM_003000.3(SDHB):c.268C>T (p.Arg90Ter)	SDHB	Pathogenic	criteria provided, multiple submitters, no conflicts
1070179	NM_000551.4(VHL):c.239G>A (p.Ser80Asn)	VHL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071196	NM_000551.4(VHL):c.244_259dup (p.Val87fs)	VHL	Pathogenic	criteria provided, single submitter
1072069	NM_000551.4(VHL):c.241_244dup (p.Arg82fs)	VHL	Pathogenic	criteria provided, single submitter
1073436	NC_000003.11:g.(?10183532)(10188330_?)del	VHL	Pathogenic	criteria provided, single submitter
1076108	NM_000551.4(VHL):c.298del (p.Thr100fs)	VHL	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 40 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
VHL	Definitive	Autosomal dominant	von Hippel-Lindau disease	12
CCND1	Supportive	Autosomal dominant	von Hippel-Lindau disease

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
EPAS1	Orphanet:247511	Autosomal dominant secondary polycythemia
EPAS1	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
EPAS1	Orphanet:324299	Multiple paragangliomas associated with polycythemia
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
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
FANCD2	Orphanet:84	Fanconi anemia
MEFV	Orphanet:117	Behçet disease
MEFV	Orphanet:3243	Sweet syndrome
MEFV	Orphanet:329967	Intermittent hydrarthrosis
MEFV	Orphanet:342	Familial Mediterranean fever

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VHL	HGNC:12687	ENSG00000134086	P40337	von Hippel-Lindau disease tumor suppressor	gencc,clinvar,civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	gencc,clinvar
EPAS1	HGNC:3374	ENSG00000116016	Q99814	Endothelial PAS domain-containing protein 1	civic_evidence
SDHB	HGNC:10681	ENSG00000117118	P21912	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	clinvar
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	clinvar
BRK1	HGNC:23057	ENSG00000254999	Q8WUW1	Protein BRICK1	clinvar
FANCD2OS	HGNC:28623	ENSG00000163705	Q96PS1	FANCD2 opposite strand protein	clinvar
FANCD2	HGNC:3585	ENSG00000144554	Q9BXW9	Fanconi anemia group D2 protein	clinvar
IRAK2	HGNC:6113	ENSG00000134070	O43187	Interleukin-1 receptor-associated kinase-like 2	clinvar
MEFV	HGNC:6998	ENSG00000103313	O15553	Pyrin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VHL	von Hippel-Lindau disease tumor suppressor	Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
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.
EPAS1	Endothelial PAS domain-containing protein 1	Transcription factor involved in the induction of oxygen regulated genes.
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).
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
BRK1	Protein BRICK1	Involved in regulation of actin and microtubule organization.
FANCD2OS	FANCD2 opposite strand protein	Reduces testosterone levels by inhibiting steroidogenic enzymes and by promoting apoptosis in Leydig cells.
FANCD2	Fanconi anemia group D2 protein	Required for maintenance of chromosomal stability.
IRAK2	Interleukin-1 receptor-associated kinase-like 2	Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization.
MEFV	Pyrin	Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma.

Protein-family classification

Druggable: 5 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.45

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	2	5.0×	0.288
Transporter	1	7.1×	0.332
Enzyme (other)	2	2.2×	0.387
Transcription factor	2	1.5×	0.490
Other/Unknown	4	0.7×	0.946

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VHL	Enzyme (other)	yes	2.3.2.B13	VHL_tumour_suppress_b/a_dom, VHL_alpha_dom, VHL_beta_dom
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
EPAS1	Transcription factor	no		PAS, Nuc_translocat, PAC
SDHB	Enzyme (other)	yes	1.3.5.1	2Fe-2S_ferredoxin-type, Succ_DH/fum_Rdtase_Fe-S, 2Fe2S_fd_BS
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
BRK1	Other/Unknown	no		BRICK1
FANCD2OS	Other/Unknown	no		FANCD2OS
FANCD2	Other/Unknown	no		FANCD2
IRAK2	Kinase	yes	2.7.10.2	Death_dom, Prot_kinase_dom, Kinase-like_dom_sf
MEFV	Transcription factor	no		Znf_B-box, B30.2/SPRY, SPRY_dom

Expression context

Cohort genes with no expression data: 0.

11 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)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	2
mononuclear cell	2
upper arm skin	2
adult organism	2
buccal mucosa cell	2
secondary oocyte	2
cortical plate	1
endometrium epithelium	1
stromal cell of endometrium	1
lower lobe of lung	1
right lung	1
apex of heart	1
cardiac ventricle	1
heart left ventricle	1
calcaneal tendon	1
colonic epithelium	1
body of pancreas	1
gall bladder	1
pancreas	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VHL	186	ubiquitous	marker	cortical plate, monocyte, mononuclear cell
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
EPAS1	298	ubiquitous	marker	right lung, lower lobe of lung, adult organism
SDHB	293	ubiquitous	marker	heart left ventricle, cardiac ventricle, apex of heart
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
CFTR	193	broad	marker	body of pancreas, gall bladder, pancreas
BRK1	256	ubiquitous	marker	sperm, upper arm skin, adult organism
FANCD2OS	120	tissue_specific	marker	left testis, right testis, testis
FANCD2	200	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, ventricular zone, secondary oocyte
IRAK2	213	ubiquitous	marker	cartilage tissue, epithelial cell of pancreas, secondary oocyte
MEFV	153	broad	marker	buccal mucosa cell, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCND1	8,328
CFTR	7,664
BRAF	7,394
SDHB	5,471
EPAS1	4,652
FANCD2	3,820
VHL	3,522
MEFV	2,217
IRAK2	2,033
BRK1	1,680

Intra-cohort edges

A	B	Sources
BRAF	VHL	biogrid_interaction
EPAS1	VHL	biogrid_interaction, intact, string_interaction

Structural data

PDB: 10 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VHL	P40337	142
BRAF	P15056	131
CFTR	P13569	58
EPAS1	Q99814	43
FANCD2	Q9BXW9	13
CCND1	P24385	11
MEFV	O15553	11
SDHB	P21912	6
BRK1	Q8WUW1	5
IRAK2	O43187	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FANCD2OS	Q96PS1	61.31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 178. Enrichment computed across 11 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	2	71.4×	0.042	IRAK2, MEFV
Disease	5	6.5×	0.042	CCND1, BRAF, BRK1, IRAK2, MEFV
RHO GTPases regulate CFTR trafficking	1	380.7×	0.055	CFTR
Signaling by MRAS-complex mutants	1	285.5×	0.055	BRAF
Replication of the SARS-CoV-1 genome	1	285.5×	0.055	VHL
Replication of the SARS-CoV-2 genome	1	285.5×	0.055	VHL
Signalling to p38 via RIT and RIN	1	228.4×	0.055	BRAF
Drug-mediated inhibition of CDK4/CDK6 activity	1	228.4×	0.055	CCND1
Negative feedback regulation of MAPK pathway	1	190.3×	0.055	BRAF
PTK6 Regulates Cell Cycle	1	190.3×	0.055	CCND1
PTK6 Expression	1	190.3×	0.055	EPAS1
ARMS-mediated activation	1	163.1×	0.055	BRAF
Prolonged ERK activation events	1	142.8×	0.055	BRAF
SHOC2 M1731 mutant abolishes MRAS complex function	1	142.8×	0.055	BRAF
Gain-of-function MRAS complexes activate RAF signaling	1	142.8×	0.055	BRAF
Signaling by FGFR3	1	114.2×	0.055	BRAF
Inflammasomes	1	114.2×	0.055	MEFV
RUNX3 regulates WNT signaling	1	114.2×	0.055	CCND1
RUNX3 regulates p14-ARF	1	114.2×	0.055	CCND1
IRAK2 mediated activation of TAK1 complex	1	114.2×	0.055	IRAK2
Cell recruitment (pro-inflammatory response)	1	114.2×	0.055	MEFV
RHOBTB3 ATPase cycle	1	114.2×	0.055	VHL
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	2	39.4×	0.055	VHL, EPAS1
Leishmania infection	2	32.6×	0.055	BRK1, MEFV
Parasitic Infection Pathways	2	32.6×	0.055	BRK1, MEFV
Innate Immune System	3	7.7×	0.055	BRK1, IRAK2, MEFV
Infectious disease	3	7.5×	0.055	BRK1, IRAK2, MEFV
Immune System	4	5.2×	0.055	CCND1, BRK1, IRAK2, MEFV
Signaling by FGFR4	1	103.8×	0.056	BRAF
Regulation of gene expression by Hypoxia-inducible Factor	1	95.2×	0.056	EPAS1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to hypoxia	3	33.1×	0.016	VHL, CCND1, EPAS1
pyroptosome complex assembly	1	766.0×	0.032	MEFV
re-entry into mitotic cell cycle	1	510.7×	0.032	CCND1
regulation of cytokine-mediated signaling pathway	1	510.7×	0.032	IRAK2
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	510.7×	0.032	BRAF
intracellular pH elevation	1	510.7×	0.032	CFTR
negative regulation of macrophage inflammatory protein 1 alpha production	1	510.7×	0.032	MEFV
response to UV-A	1	383.0×	0.032	CCND1
negative regulation of testosterone biosynthetic process	1	383.0×	0.032	FANCD2OS
regulation of CD40 signaling pathway	1	383.0×	0.032	FANCD2
succinate metabolic process	1	306.4×	0.032	SDHB
mitochondrial electron transport, succinate to ubiquinone	1	306.4×	0.032	SDHB
transepithelial water transport	1	306.4×	0.032	CFTR
myoblast fate commitment	1	306.4×	0.032	EPAS1
positive regulation of axon regeneration	1	306.4×	0.032	BRAF
positive regulation of enamel mineralization	1	306.4×	0.032	CFTR
negative regulation of synaptic vesicle exocytosis	1	306.4×	0.032	BRAF
regulation of actin polymerization or depolymerization	1	255.3×	0.032	BRK1
response to vitamin E	1	255.3×	0.032	CCND1
positive regulation of mammary gland epithelial cell proliferation	1	255.3×	0.032	CCND1
CD4-positive, alpha-beta T cell differentiation	1	255.3×	0.032	BRAF
regulation of cellular response to hypoxia	1	255.3×	0.032	VHL
myeloid progenitor cell differentiation	1	218.9×	0.032	BRAF
Toll signaling pathway	1	218.9×	0.032	IRAK2
response to leptin	1	218.9×	0.032	CCND1
positive regulation of D-glucose transmembrane transport	1	191.5×	0.032	BRAF
regulation of interleukin-1 beta production	1	191.5×	0.032	MEFV
head morphogenesis	1	191.5×	0.032	BRAF
positive regulation of Arp2/3 complex-mediated actin nucleation	1	191.5×	0.032	BRK1
negative regulation of neuron apoptotic process	2	20.2×	0.032	CCND1, BRAF

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Belzutifan	Approved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dovitinib, Sunitinib, Vatalanib.

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 6

Druggability breadth: 10 of 11 evidence-associated genes (91%) 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
BRAF	VEMURAFENIB
CFTR	IVACAFTOR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRAF	48	4
CCND1	35	4
CFTR	14	4
VHL	7	4
EPAS1	7	4
SDHB	0	0
BRK1	0	0
FANCD2OS	0	0
FANCD2	0	0
IRAK2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OSIMERTINIB	4	VHL
BRIGATINIB	4	VHL
CRIZOTINIB	4	VHL
ADAGRASIB	4	VHL
PALBOCICLIB	4	CCND1
ABEMACICLIB	4	BRAF, CCND1
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
BELZUTIFAN	4	EPAS1
EMETINE	4	EPAS1
DOXORUBICIN	4	EPAS1
TOPOTECAN	4	EPAS1
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
VHL	3,575	Binding:3482, Functional:54, ADMET:39
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
CCND1	576	Binding:574, Functional:1, ADMET:1
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
EPAS1	241	Binding:233, Functional:8
SDHB	4	Binding:4
FANCD2	2	Binding:2
IRAK2	2	Binding:2
BRK1	1	Binding:1
MEFV	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
VHL	2.3.2.B13
SDHB	1.3.5.1	succinate dehydrogenase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase
IRAK2	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
VHL	3,575
CCND1	576
EPAS1	241
BRAF	1,442
CFTR	520

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

Chemical tractability of cohort targets

28 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
OSIMERTINIB	4	VHL
BRIGATINIB	4	VHL
CRIZOTINIB	4	VHL
ADAGRASIB	4	VHL
ABEMACICLIB	4	BRAF, CCND1
RIBOCICLIB	4	CCND1
TRILACICLIB	4	CCND1
EMETINE	4	EPAS1
DOXORUBICIN	4	EPAS1
TOPOTECAN	4	EPAS1
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	VHL, CCND1, EPAS1, BRAF, CFTR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	SDHB, IRAK2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	BRK1, FANCD2OS, FANCD2, MEFV

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SDHB	4	—
BRK1	1	—
FANCD2OS	0	—
FANCD2	2	—
IRAK2	2	—
MEFV	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 45.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	24
PHASE2	12
PHASE1/PHASE2	3
PHASE1	3
EARLY_PHASE1	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07405164	PHASE3	RECRUITING	Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)
NCT03401788	PHASE2	ACTIVE_NOT_RECRUITING	A Phase 2 Study of Belzutifan (PT2977, MK-6482) for the Treatment of Von Hippel Lindau (VHL) Disease-Associated Renal Cell Carcinoma (RCC) (MK-6482-004)
NCT04074135	PHASE2	RECRUITING	Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors
NCT04924075	PHASE2	RECRUITING	Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
NCT07167329	PHASE2	RECRUITING	Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial
NCT00052013	PHASE2	COMPLETED	Treatment of Von Hippel-Lindau (VHL)-Related Hemangioblastoma With PTK787/ZK 222584
NCT00330564	PHASE2	TERMINATED	Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow
NCT00470977	PHASE1/PHASE2	COMPLETED	Treatment of Exudative and Vasogenic Chorioretinal Diseases Including Variants of AMD and Other CNV Related Maculopathy
NCT00673816	PHASE1/PHASE2	TERMINATED	Sunitinib Malate to Treat Advanced Eye Disease in Patients With Von Hippel-Lindau Syndrome
NCT01168440	PHASE2	COMPLETED	Study of Sunitinib in Patients With Von Hippel-Lindau (VHL) Disease
NCT01266070	PHASE2	TERMINATED	TKI 258 in Von Hippel-Lindau Syndrome (VHL)
NCT01436227	PHASE2	COMPLETED	Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome
NCT01967537	PHASE2	COMPLETED	Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors
NCT02859441	PHASE1/PHASE2	COMPLETED	A Phase I/II Trial for Intravitreous Treatment of Severe Ocular Von Hippel-Lindau Disease Using a Combination of the PDGF Antagonist E10030 and the VEGF Antagonist Ranibizumab
NCT03108066	PHASE2	COMPLETED	MK-3795 (PT2385) for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma (MK-3795-003)
NCT05810246	PHASE2	UNKNOWN	68Ga-NY104 PET/CT in Von Hippel-Lindau Disease
NCT00089765	PHASE1	COMPLETED	Ranibizumab Injections to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome
NCT02108002	PHASE1	COMPLETED	Effect of Vorinostat on Nervous System Hemangioblastomas in Von Hippel-Lindau Disease (Missense Mutation Only)
NCT05843305	PHASE1	UNKNOWN	A Study of BPI-452080 in Subjects With Solid Tumors
NCT01015300	EARLY_PHASE1	TERMINATED	Bevacizumab (Avastin) in Unresectable/Recurrent Hemangioblastoma From Von-Hippel-Lindau Disease
NCT03001349	EARLY_PHASE1	TERMINATED	68Ga-DOTA-TOC PET/CT in Imaging Participants With Neuroendocrine Tumors
NCT00102544	Not specified	ENROLLING_BY_INVITATION	Use of Tracking Devices to Locate Abnormalities During Invasive Procedures
NCT01496625	Not specified	RECRUITING	National Eye Institute Biorepository for Retinal Diseases
NCT02420067	Not specified	RECRUITING	Screening for Endolymphatic Sac Tumours (ELSTs) in Von Hippel-Lindau (vHL) Patients
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03749980	Not specified	RECRUITING	MyVHL: Patient Natural History Study
NCT04458935	Not specified	ACTIVE_NOT_RECRUITING	Retrospective Case Series of Trans-scleral Cryotherapy for Retinal Hemangioblastoma
NCT05424016	Not specified	RECRUITING	Propranolol and Von Hippel-Lindau Disease
NCT05737602	Not specified	ENROLLING_BY_INVITATION	Promoting Stress Management and Resilience Among Individuals With Von Hippel- Lindau Disease
NCT05955014	Not specified	RECRUITING	Data Collection Protocol for Patients With Von Hippel Lindau Disease
NCT06194669	Not specified	RECRUITING	Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells
NCT06195150	Not specified	ACTIVE_NOT_RECRUITING	Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau Related Renal Cancer
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients
NCT06573723	Not specified	RECRUITING	Institutional Registry of Rare Diseases
NCT07557225	Not specified	RECRUITING	18F-T2 PET/CT Imaging for CAIX Positive Solid Tumors
NCT00001803	Not specified	TERMINATED	Von Hippel-Lindau Disease Genetic Epidemiology Study
NCT00062166	Not specified	COMPLETED	Natural History and Management of Pancreatic Lesions in Von Hippel-Lindau Disease
NCT00075348	Not specified	COMPLETED	Genetic Study to Identify Gene Mutations in Participants Previously Enrolled in Clinical Trial NCI-99-C-0053 Who Have Von Hippel-Lindau Syndrome or Are at Risk for Von Hippel-Lindau Syndrome
NCT00970970	Not specified	COMPLETED	Visualizing Vascular Endothelial Growth Factor (VEGF) Producing Lesions in Von Hippel-Lindau Disease
NCT03979833	Not specified	UNKNOWN	Drivers of Hypoxia-induced Angiogenesis in Tumor Development

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BELZUTIFAN	4	5
SUNITINIB	4	3
CABOZANTINIB	4	1
EDOTREOTIDE GALLIUM GA-68	4	1
LENVATINIB	4	1
PALBOCICLIB	4	1
PAZOPANIB HYDROCHLORIDE	4	1
DOVITINIB	3	1
PEGPLERANIB SODIUM	3	1
VATALANIB	3	1
CHEMBL365847	0	1
CHEMBL4215501	0	1
CHEMBL4849721	0	1
CHEMBL4578973	0	1
EXELIXIS	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items; also 1598 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
EPAS1 Overexpression	Belzutifan	Sensitivity/Response	CIViC B	EID12948
VHL N78S (c.233A>G)	Sunitinib	Sensitivity/Response	CIViC C	EID6429