Ganglioglioma

Summary

Ganglioglioma (MONDO:0016733) is a disease with 5 cohort genes and 9 clinical trials. Molecularly, BCR::NTRK2 Fusion confers sensitivity to Entrectinib in Ganglioglioma (CIViC Level C); 5 further subtype–drug associations are mapped below. Top therapeutic interventions include dabrafenib and trametinib.

At a glance

• Cohort genes: 5
• ClinVar variants: 1
• Clinical trials: 9
• Precision-medicine evidence (CIViC): 6 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ganglioglioma
Mondo ID	MONDO:0016733
EFO	EFO:0003094
MeSH	D018303
Orphanet	251949
DOID	DOID:5078
ICD-11	1287417975
NCIT	C3788
SNOMED CT	87191000119100
UMLS	C0206716
MedGen	60216
GARD	0002430
MedDRA	10017701
Is cancer (heuristic)	no

Also known as: adult ganglioglioma · childhood ganglioglioma · ganglioglioma · mixed cell tumors containing both neural ganglionic cells and neural glial cell components · mixed cell tumours containing both neural ganglionic cells and neural glial cell components

Data availability: 1 ClinVar variant · 2 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 › ganglioglioma

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

Subtypes (2): nasal ganglioglioma, anaplastic 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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
620598	NM_004656.4(BAP1):c.1833G>C (p.Glu611Asp)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
IDH1	Orphanet:163634	Maffucci syndrome
IDH1	Orphanet:251576	Gliosarcoma
IDH1	Orphanet:251579	Giant cell glioblastoma
IDH1	Orphanet:296	Ollier disease
IDH1	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
IDH1	Orphanet:99646	Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria
BAP1	Orphanet:2495	Meningioma
BAP1	Orphanet:289539	BAP1-related tumor predisposition syndrome
BAP1	Orphanet:39044	Uveal melanoma
BAP1	Orphanet:50251	Pleural mesothelioma
BAP1	Orphanet:528084	Non-specific syndromic intellectual disability
BAP1	Orphanet:618	Familial melanoma

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	3
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
H3-3A	HGNC:4764	ENSG00000163041	P84243	Histone H3.3	civic_evidence
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	civic_evidence
MAGI1	HGNC:946	ENSG00000151276	Q96QZ7	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1	clinvar
BAP1	HGNC:950	ENSG00000163930	Q92560	Ubiquitin carboxyl-terminal hydrolase BAP1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
H3-3A	Histone H3.3	Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes.
IDH1	Isocitrate dehydrogenase [NADP] cytoplasmic	Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase.
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.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.8

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	11.1×	0.048
Protease	1	7.3×	0.259
Enzyme (other)	1	2.4×	0.471
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
H3-3A	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, Histone-fold
IDH1	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
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

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
buccal mucosa cell	1
calcaneal tendon	1
colonic epithelium	1
ganglionic eminence	1
monocyte	1
adrenal tissue	1
corpus epididymis	1
jejunal mucosa	1
corpus callosum	1
sural nerve	1
left testis	1
right frontal lobe	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
H3-3A	134	ubiquitous	marker	ganglionic eminence, monocyte, ventricular zone
IDH1	294	ubiquitous	marker	corpus epididymis, jejunal mucosa, adrenal tissue
MAGI1	133	ubiquitous	marker	ventricular zone, sural nerve, corpus callosum
BAP1	253	ubiquitous	marker	left testis, right testis, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRAF	7,394
IDH1	5,464
BAP1	3,373
MAGI1	2,043
H3-3A	1,595

Intra-cohort edges

A	B	Sources
BAP1	BRAF	intact

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRAF	P15056	131
H3-3A	P84243	103
IDH1	O75874	61
MAGI1	Q96QZ7	16
BAP1	Q92560	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 91. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1	2855.0×	0.025	IDH1
NADPH regeneration	1	1427.5×	0.025	IDH1
NFE2L2 regulating TCA cycle genes	1	951.7×	0.025	IDH1
Signaling by MRAS-complex mutants	1	713.8×	0.025	BRAF
Signalling to p38 via RIT and RIN	1	571.0×	0.025	BRAF
Negative feedback regulation of MAPK pathway	1	475.8×	0.025	BRAF
ARMS-mediated activation	1	407.9×	0.025	BRAF
Prolonged ERK activation events	1	356.9×	0.025	BRAF
SHOC2 M1731 mutant abolishes MRAS complex function	1	356.9×	0.025	BRAF
Gain-of-function MRAS complexes activate RAF signaling	1	356.9×	0.025	BRAF
Signaling by FGFR3	1	285.5×	0.029	BRAF
Signaling by FGFR4	1	259.6×	0.029	BRAF
Frs2-mediated activation	1	237.9×	0.029	BRAF
Signaling by FGFR1	1	203.9×	0.032	BRAF
Spry regulation of FGF signaling	1	178.4×	0.034	BRAF
Signalling to ERKs	1	150.3×	0.038	BRAF
DNA Double Strand Break Response	1	119.0×	0.042	BAP1
Negative regulation of FGFR3 signaling	1	109.8×	0.042	BRAF
Signaling by RAS mutants	1	105.7×	0.042	BRAF
Negative regulation of FGFR4 signaling	1	102.0×	0.042	BRAF
Signaling by FGFR2	1	102.0×	0.042	BRAF
Negative regulation of FGFR1 signaling	1	92.1×	0.042	BRAF
Negative regulation of FGFR2 signaling	1	92.1×	0.042	BRAF
Signaling by FGFR	1	86.5×	0.042	BRAF
RAF activation	1	84.0×	0.042	BRAF
Signaling by high-kinase activity BRAF mutants	1	79.3×	0.042	BRAF
MAP2K and MAPK activation	1	71.4×	0.042	BRAF
Signaling by RAF1 mutants	1	69.6×	0.042	BRAF
Replacement of protamines by nucleosomes in the male pronucleus	1	68.0×	0.042	H3-3A
Negative regulation of MAPK pathway	1	66.4×	0.042	BRAF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
thrombocyte differentiation	1	3370.4×	0.010	BAP1
nucleate erythrocyte differentiation	1	3370.4×	0.010	BAP1
regulation of phospholipid catabolic process	1	3370.4×	0.010	IDH1
glyoxylate cycle	1	1685.2×	0.010	IDH1
leukocyte proliferation	1	1685.2×	0.010	BAP1
regulation of phospholipid biosynthetic process	1	1685.2×	0.010	IDH1
platelet morphogenesis	1	1123.5×	0.010	BAP1
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	1123.5×	0.010	BRAF
macrophage homeostasis	1	1123.5×	0.010	BAP1
negative regulation of chromosome condensation	1	842.6×	0.010	H3-3A
isocitrate metabolic process	1	674.1×	0.010	IDH1
NADPH regeneration	1	674.1×	0.010	IDH1
pericentric heterochromatin formation	1	674.1×	0.010	H3-3A
positive regulation of axon regeneration	1	674.1×	0.010	BRAF
negative regulation of synaptic vesicle exocytosis	1	674.1×	0.010	BRAF
CD4-positive, alpha-beta T cell differentiation	1	561.7×	0.011	BRAF
myeloid progenitor cell differentiation	1	481.5×	0.011	BRAF
positive regulation of D-glucose transmembrane transport	1	421.3×	0.011	BRAF
myeloid cell apoptotic process	1	421.3×	0.011	BAP1
head morphogenesis	1	421.3×	0.011	BRAF
neutrophil differentiation	1	374.5×	0.011	BAP1
monoubiquitinated protein deubiquitination	1	374.5×	0.011	BAP1
common myeloid progenitor cell proliferation	1	374.5×	0.011	BAP1
establishment of protein localization to membrane	1	374.5×	0.011	BRAF
regulation of cytokine production involved in inflammatory response	1	374.5×	0.011	BAP1
NADP+ metabolic process	1	306.4×	0.012	IDH1
negative regulation of fibroblast migration	1	306.4×	0.012	BRAF
subtelomeric heterochromatin formation	1	306.4×	0.012	H3-3A
endothelial cell apoptotic process	1	259.3×	0.014	BRAF
regulation of T cell differentiation	1	240.7×	0.014	BRAF

Therapeutics

Drug target analysis

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

Druggability breadth: 5 of 5 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
BRAF	VEMURAFENIB
IDH1	ENASIDENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRAF	48	4
IDH1	10	4
H3-3A	0	0
MAGI1	0	0
BAP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
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
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
ENASIDENIB	4	IDH1
IVOSIDENIB	4	IDH1
VORASIDENIB	4	IDH1
OLUTASIDENIB	4	IDH1
MASITINIB	3	BRAF
AVUTOMETINIB	3	BRAF
NAPORAFENIB	3	BRAF
QUERCETIN	3	BRAF
MOTESANIB	3	BRAF
DORAMAPIMOD	2	BRAF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
IDH1	488	Binding:475, Functional:12, ADMET:1
H3-3A	6	Binding:6
BAP1	5	Binding:4, Functional:1
MAGI1	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)
BAP1	3.4.19.12	ubiquitinyl hydrolase 1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRAF	1,442
IDH1	488

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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)
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
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
ENASIDENIB	4	IDH1
IVOSIDENIB	4	IDH1
VORASIDENIB	4	IDH1
OLUTASIDENIB	4	IDH1
MASITINIB	3	BRAF
AVUTOMETINIB	3	BRAF
NAPORAFENIB	3	BRAF
QUERCETIN	3	BRAF
MOTESANIB	3	BRAF
DORAMAPIMOD	2	BRAF

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BRAF, IDH1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	MAGI1, BAP1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	H3-3A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
H3-3A	6	—
MAGI1	4	—
BAP1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE2	2
PHASE1	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT02684058	PHASE2	COMPLETED	Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors
NCT03152318	PHASE1	ACTIVE_NOT_RECRUITING	A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2
NCT01999270	PHASE1	COMPLETED	Evaluation of FDOPA-PET/MRI in Pediatric Patients With CNS Tumors
NCT04065776	Not specified	RECRUITING	Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma
NCT04648462	Not specified	RECRUITING	Proton Therapy Research Infrastructure- ProTRAIT- Neuro-oncology
NCT06915649	Not specified	RECRUITING	Exploration and Evaluation of Amygdalo-Hippocampectomy According to Prof. Coubes’ Technique: An Anatomical, Clinical, and Educational Approach
NCT03900689	Not specified	COMPLETED	Social Determinants of Health in Glioblastoma Population

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DABRAFENIB	4	2
TRAMETINIB	4	2
CHEMBL5433950	0	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 6 predictive associations from 6 curated evidence items; also 3 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
BCR::NTRK2 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID12053
BRAF T599dup	Trametinib + Dabrafenib	Sensitivity/Response	CIViC C	EID9789
BRAF V600E	Vemurafenib + Cobimetinib	Sensitivity/Response	CIViC C	EID11310
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC C	EID3778
BRAF V600E AND CDKN2A Deletion AND CDKN2B Deletion AND TET2 E796K AND BAX L76R AND AXIN2 P455K	Cobimetinib + Vemurafenib	Sensitivity/Response	CIViC C	EID11314
EML1::NTRK2 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID11852