Trilateral retinoblastoma

Summary

Trilateral retinoblastoma (MONDO:0003073) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

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

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	trilateral retinoblastoma
Mondo ID	MONDO:0003073
DOID	DOID:4647
NCIT	C7019
UMLS	C2608045
MedGen	392856
GARD	0023353
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › nervous system cancer › sensory system cancer › ocular cancer › retinal cancer › retinal cell cancer › retinoblastoma › trilateral retinoblastoma

Related subtypes (6): bilateral retinoblastoma, unilateral retinoblastoma, intraocular retinoblastoma, extraocular retinoblastoma, hereditary retinoblastoma, non-hereditary retinoblastoma

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
13090	NM_000321.3(RB1):c.1666C>T (p.Arg556Ter)	RB1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RB1	Orphanet:1587	Monosomy 13q14 syndrome
RB1	Orphanet:357027	Hereditary retinoblastoma
RB1	Orphanet:357034	Non-hereditary retinoblastoma
RB1	Orphanet:668	Osteosarcoma
RB1	Orphanet:70573	Small cell lung cancer

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
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_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
choroid plexus epithelium	1
epithelium of nasopharynx	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RB1	4,374

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RB1	P06400	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Defective translocation of RB1 mutants to the nucleus	1	11420.0×	0.002	RB1
Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes	1	2855.0×	0.002	RB1
Replication of the SARS-CoV-1 genome	1	2855.0×	0.002	RB1
Replication of the SARS-CoV-2 genome	1	2855.0×	0.002	RB1
Positive Regulation of CDH1 Gene Transcription	1	951.7×	0.004	RB1
Inhibition of replication initiation of damaged DNA by RB1/E2F1	1	815.7×	0.004	RB1
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	671.8×	0.004	RB1
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1	634.4×	0.004	RB1
Aberrant regulation of mitotic exit in cancer due to RB1 defects	1	519.1×	0.004	RB1
RUNX2 regulates osteoblast differentiation	1	456.8×	0.004	RB1
Oncogene Induced Senescence	1	335.9×	0.005	RB1
Nuclear events stimulated by ALK signaling in cancer	1	326.3×	0.005	RB1
Cyclin E associated events during G1/S transition	1	285.5×	0.005	RB1
Cyclin A:Cdk2-associated events at S phase entry	1	265.6×	0.005	RB1
Cyclin D associated events in G1	1	233.1×	0.005	RB1
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1	170.4×	0.007	RB1
Condensation of Prophase Chromosomes	1	156.4×	0.007	RB1
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	82.8×	0.012	RB1

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
sister chromatid biorientation	1	5617.3×	0.002	RB1
glial cell apoptotic process	1	5617.3×	0.002	RB1
maintenance of mitotic sister chromatid cohesion	1	4213.0×	0.002	RB1
regulation of lipid kinase activity	1	4213.0×	0.002	RB1
positive regulation of extracellular matrix organization	1	4213.0×	0.002	RB1
positive regulation of collagen fibril organization	1	4213.0×	0.002	RB1
negative regulation of myofibroblast differentiation	1	4213.0×	0.002	RB1
negative regulation of hepatocyte apoptotic process	1	2808.7×	0.002	RB1
enucleate erythrocyte differentiation	1	2106.5×	0.002	RB1
protein localization to chromosome, centromeric region	1	2106.5×	0.002	RB1
positive regulation of transcription regulatory region DNA binding	1	2106.5×	0.002	RB1
negative regulation of glial cell proliferation	1	1685.2×	0.003	RB1
cell morphogenesis involved in neuron differentiation	1	1532.0×	0.003	RB1
positive regulation of macrophage differentiation	1	1203.7×	0.003	RB1
positive regulation of mitotic metaphase/anaphase transition	1	1203.7×	0.003	RB1
hepatocyte apoptotic process	1	1053.2×	0.003	RB1
striated muscle cell differentiation	1	991.3×	0.003	RB1
glial cell proliferation	1	887.0×	0.003	RB1
negative regulation of protein kinase activity	1	842.6×	0.003	RB1
myoblast differentiation	1	842.6×	0.003	RB1
neuron maturation	1	802.5×	0.003	RB1
chromosome organization	1	581.1×	0.004	RB1
tissue homeostasis	1	561.7×	0.004	RB1
negative regulation of apoptotic signaling pathway	1	561.7×	0.004	RB1
digestive tract development	1	526.6×	0.004	RB1
negative regulation of smoothened signaling pathway	1	455.5×	0.005	RB1
aortic valve morphogenesis	1	432.1×	0.005	RB1
negative regulation of G1/S transition of mitotic cell cycle	1	358.6×	0.005	RB1
skeletal muscle cell differentiation	1	343.9×	0.005	RB1
negative regulation of cold-induced thermogenesis	1	343.9×	0.005	RB1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · 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).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RB1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EBVACICLIB	2	RB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RB1	59	Binding:59

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

1 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)
EBVACICLIB	2	RB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	RB1
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06367530	Not specified	RECRUITING	Trilateral Retinoblastoma: Incidence and Outcomes