Rosette-forming glioneuronal tumor of fourth ventricule

Summary

Rosette-forming glioneuronal tumor of fourth ventricule (MONDO:0016736) is a cancer with 4 cohort genes (2 CIViC-evidence somatic drivers; 4 ClinVar predisposition records) and 1 clinical trial. Top therapeutic interventions include dabrafenib and trametinib.

At a glance

• Classification: Cancer
• Cohort genes: 4
• ClinVar variants: 4
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rosette-forming glioneuronal tumor of fourth ventricule
Mondo ID	MONDO:0016736
Orphanet	251975
DOID	DOID:0081284
NCIT	C129431
UMLS	C4331262
MedGen	1377578
GARD	0013593
Is cancer (heuristic)	yes

Also known as: DNT of the cerebellum · dysembryoplastic neuroepithelial tumor of cerebellum · dysembryoplastic neuroepithelial tumour of cerebellum · RGNT · rosette-forming glioneuronal tumor

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › nervous system neoplasm › neuroepithelial neoplasm › mixed neuronal-glial tumor › rosette-forming glioneuronal tumor of fourth ventricule

Related subtypes (11): ganglioneuroma, dysembryoplastic neuroepithelial tumor, extraventricular neurocytoma, gangliocytoma, desmoplastic infantile astrocytoma/ganglioglioma, ganglioglioma, papillary glioneuronal tumor, Lhermitte-Duclos disease, central neurocytoma, desmoplastic infantile astrocytoma, desmoplastic infantile ganglioglioma

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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
224896	NM_023110.3(FGFR1):c.1638C>A (p.Asn546Lys)	FGFR1	Pathogenic	criteria provided, multiple submitters, no conflicts
13652	NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg)	PIK3CA	Pathogenic	reviewed by expert panel
424630	NM_006741.4(PPP1R1A):c.372_373delinsCA (p.Glu124_Ser125delinsAspThr)	PPP1R1A	Uncertain significance	criteria provided, single submitter
424631	NM_207111.4(RNF216):c.2468G>A (p.Arg823His)	RNF216	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 33 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF216	Orphanet:1173	Cerebellar ataxia-hypogonadism syndrome
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CA	Orphanet:714737	Diffuse capillary malformation with overgrowth
PIK3CA	Orphanet:90308	Capillary-lymphatic-venous malformation with segmental distribution
PIK3CA	Orphanet:99802	Hemimegalencephaly

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF216	HGNC:21698	ENSG00000011275	Q9NWF9	E3 ubiquitin-protein ligase RNF216	clinvar
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar
PPP1R1A	HGNC:9286	ENSG00000135447	Q13522	Protein phosphatase 1 regulatory subunit 1A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF216	E3 ubiquitin-protein ligase RNF216	E3 ubiquitin ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their ubiquitination.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PPP1R1A	Protein phosphatase 1 regulatory subunit 1A	Inhibitor of protein-phosphatase 1.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.5

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	13.9×	0.022
Transcription factor	1	2.1×	0.605
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF216	Transcription factor	no		IBR_dom, Znf_RING/FYVE/PHD, TRIAD_supradom
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PPP1R1A	Other/Unknown	no		PPP1R1A/B/C

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
right testis	1
buccal mucosa cell	1
stromal cell of endometrium	1
adrenal tissue	1
tendon	1
diaphragm	1
hindlimb stylopod muscle	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF216	278	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PPP1R1A	253	broad	marker	triceps brachii, diaphragm, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR1	5,693
PIK3CA	5,157
RNF216	1,268
PPP1R1A	847

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3CA	P42336	135
FGFR1	P11362	83
RNF216	Q9NWF9	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PPP1R1A	Q13522	67.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 79. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PI-3K cascade:FGFR1	2	346.1×	8e-04	FGFR1, PIK3CA
Signaling by FGFR1 in disease	2	195.2×	0.001	FGFR1, PIK3CA
PI3K Cascade	2	181.3×	0.001	FGFR1, PIK3CA
Constitutive Signaling by Aberrant PI3K in Cancer	2	84.6×	0.004	FGFR1, PIK3CA
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	64.5×	0.005	FGFR1, PIK3CA
Signaling by FGFR1 amplification mutants	1	1903.3×	0.007	FGFR1
PIP3 activates AKT signaling	2	44.5×	0.007	FGFR1, PIK3CA
RAF/MAP kinase cascade	2	40.7×	0.008	FGFR1, PIK3CA
FGFR1c and Klotho ligand binding and activation	1	951.7×	0.008	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	951.7×	0.008	FGFR1
MET activates PI3K/AKT signaling	1	634.4×	0.010	PIK3CA
Activated NTRK3 signals through PI3K	1	634.4×	0.010	PIK3CA
Activated NTRK2 signals through PI3K	1	543.8×	0.010	PIK3CA
Signaling by LTK in cancer	1	543.8×	0.010	PIK3CA
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	475.8×	0.010	FGFR1
FGFR1b ligand binding and activation	1	423.0×	0.010	FGFR1
PI3K/AKT activation	1	423.0×	0.010	PIK3CA
IRS-mediated signalling	1	346.1×	0.010	PIK3CA
PI3K events in ERBB4 signaling	1	346.1×	0.010	PIK3CA
Co-stimulation by ICOS	1	346.1×	0.010	PIK3CA
Signaling by activated point mutants of FGFR1	1	317.2×	0.010	FGFR1
Signaling by FGFR4 in disease	1	317.2×	0.010	PIK3CA
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	317.2×	0.010	PIK3CA
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	292.8×	0.010	PIK3CA
Signaling by PDGFRA extracellular domain mutants	1	292.8×	0.010	PIK3CA
Signaling by LTK	1	292.8×	0.010	PIK3CA
FGFR1c ligand binding and activation	1	253.8×	0.010	FGFR1
Signaling by FLT3 ITD and TKD mutants	1	253.8×	0.010	PIK3CA
Constitutive Signaling by EGFRvIII	1	237.9×	0.010	PIK3CA
PI3K events in ERBB2 signaling	1	223.9×	0.010	PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
phosphatidylinositol-mediated signaling	2	351.1×	0.001	FGFR1, PIK3CA
response to muscle inactivity	1	4213.0×	0.007	PIK3CA
response to butyrate	1	4213.0×	0.007	PIK3CA
vitamin D3 metabolic process	1	2106.5×	0.007	FGFR1
positive regulation of mitotic cell cycle DNA replication	1	2106.5×	0.007	FGFR1
positive regulation of parathyroid hormone secretion	1	2106.5×	0.007	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	2106.5×	0.007	FGFR1
regulation of phosphate transport	1	1404.3×	0.007	FGFR1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	1404.3×	0.007	FGFR1
response to L-leucine	1	1404.3×	0.007	PIK3CA
regulation of lateral mesodermal cell fate specification	1	1404.3×	0.007	FGFR1
cellular response to hydrostatic pressure	1	1404.3×	0.007	PIK3CA
ventricular zone neuroblast division	1	1053.2×	0.007	FGFR1
negative regulation of fibroblast growth factor production	1	1053.2×	0.007	FGFR1
positive regulation of phospholipase activity	1	842.6×	0.007	FGFR1
regulation of interferon-beta production	1	842.6×	0.007	RNF216
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	842.6×	0.007	FGFR1
diphosphate metabolic process	1	842.6×	0.007	FGFR1
negative regulation of actin filament depolymerization	1	702.2×	0.007	PIK3CA
chordate embryonic development	1	702.2×	0.007	FGFR1
regulation of cellular respiration	1	702.2×	0.007	PIK3CA
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway	1	702.2×	0.007	FGFR1
cementum mineralization	1	601.9×	0.007	FGFR1
regulation of actin filament organization	1	601.9×	0.007	PIK3CA
autosome genomic imprinting	1	601.9×	0.007	PIK3CA
negative regulation of fibroblast apoptotic process	1	601.9×	0.007	PIK3CA
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	39.2×	0.007	FGFR1, PIK3CA
angiogenesis	2	31.2×	0.007	FGFR1, PIK3CA
cell migration	2	30.8×	0.007	FGFR1, PIK3CA
regulation of defense response to virus by host	1	526.6×	0.008	RNF216

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
FGFR1	PONATINIB
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
PIK3CA	67	4
RNF216	0	0
PPP1R1A	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1, PIK3CA
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1, PIK3CA
DASATINIB	4	FGFR1, PIK3CA
MIDOSTAURIN	4	FGFR1, PIK3CA
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, 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
FGFR1	1,465
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1, PIK3CA
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1
SUNITINIB	4	FGFR1, PIK3CA
DASATINIB	4	FGFR1, PIK3CA
MIDOSTAURIN	4	FGFR1, PIK3CA
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	FGFR1, PIK3CA
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	2	RNF216, PPP1R1A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RNF216	0	—
PPP1R1A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DABRAFENIB	4	1
TRAMETINIB	4	1
CHEMBL5433950	0	1