Retinal hemangioblastoma

Summary

Retinal hemangioblastoma (MONDO:0003343) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include vatalanib.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinal hemangioblastoma
Mondo ID	MONDO:0003343
DOID	DOID:5240
NCIT	C39783
UMLS	C0730303
MedGen	152677
GARD	0023461
Anatomy (UBERON)	UBERON:0004864
Is cancer (heuristic)	no

Also known as: hemangioblastoma of vasculature of retina · retinal capillary hemangioblastoma · retinal hemangioblastoma · vasculature of retina hemangioblastoma

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal vascular disorder › retinal hemangioblastoma

Related subtypes (11): retinal microaneurysm, retinal vascular occlusion, retinal telangiectasia, diabetic retinopathy, retinal vasculitis, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, familial retinal arterial macroaneurysm, vasoproliferative tumor of retina, exudative vitreoretinopathy, arteriosclerotic retinopathy, perifoveal exudative vascular anomalous complex

Subtypes (1): isolated retinal racemose hemangioma

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
182975	NM_000551.4(VHL):c.194C>T (p.Ser65Leu)	VHL	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VHL	HGNC:12687	ENSG00000134086	P40337	von Hippel-Lindau disease tumor suppressor	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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VHL	186	ubiquitous	marker	cortical plate, monocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VHL	3,522

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VHL	P40337	142

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Replication of the SARS-CoV-1 genome	1	2855.0×	0.001	VHL
Replication of the SARS-CoV-2 genome	1	2855.0×	0.001	VHL
RHOBTB3 ATPase cycle	1	1142.0×	0.002	VHL
SUMOylation of ubiquitinylation proteins	1	292.8×	0.006	VHL
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	1	196.9×	0.007	VHL
Neddylation	1	47.4×	0.025	VHL
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.027	VHL

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of cellular response to hypoxia	1	2808.7×	0.007	VHL
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.009	VHL
negative regulation of transcription elongation by RNA polymerase II	1	766.0×	0.009	VHL
amyloid fibril formation	1	601.9×	0.009	VHL
negative regulation of signal transduction	1	374.5×	0.010	VHL
negative regulation of TORC1 signaling	1	324.1×	0.010	VHL
positive regulation of cell differentiation	1	267.5×	0.010	VHL
negative regulation of autophagy	1	259.3×	0.010	VHL
cell morphogenesis	1	157.5×	0.015	VHL
cellular response to hypoxia	1	121.2×	0.017	VHL
regulation of gene expression	1	83.4×	0.023	VHL
negative regulation of gene expression	1	69.1×	0.024	VHL
protein stabilization	1	66.9×	0.024	VHL
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.029	VHL
negative regulation of cell population proliferation	1	42.1×	0.032	VHL
protein ubiquitination	1	41.4×	0.032	VHL
negative regulation of apoptotic process	1	34.8×	0.034	VHL
proteolysis	1	34.2×	0.034	VHL
regulation of DNA-templated transcription	1	31.6×	0.035	VHL
positive regulation of DNA-templated transcription	1	27.9×	0.038	VHL
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	VHL

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VHL	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OSIMERTINIB	4	VHL
BRIGATINIB	4	VHL
CRIZOTINIB	4	VHL
ADAGRASIB	4	VHL
ZIMLOVISERTIB	2	VHL
FORETINIB	2	VHL
DT-2216	1	VHL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
VHL	3,575	Binding:3482, Functional:54, ADMET:39

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
VHL	2.3.2.B13

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

7 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
ZIMLOVISERTIB	2	VHL
FORETINIB	2	VHL
DT-2216	1	VHL

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	VHL
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00052013	PHASE2	COMPLETED	Treatment of Von Hippel-Lindau (VHL)-Related Hemangioblastoma With PTK787/ZK 222584
NCT04458935	Not specified	ACTIVE_NOT_RECRUITING	Retrospective Case Series of Trans-scleral Cryotherapy for Retinal Hemangioblastoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VATALANIB	3	1