Multinodular and vacuolating neuronal tumor

Summary

Multinodular and vacuolating neuronal tumor (MONDO:0858957) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers).

At a glance

• Classification: Cancer
• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multinodular and vacuolating neuronal tumor
Mondo ID	MONDO:0858957
DOID	DOID:0081303
NCIT	C129427
UMLS	C4330721
MedGen	1372723
Is cancer (heuristic)	yes

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › benign neoplasm › nervous system benign neoplasm › central nervous system organ benign neoplasm › multinodular and vacuolating neuronal tumor

Related subtypes (12): central nervous system chondroma, central nervous system hemangioma, central nervous system leiomyoma, central nervous system lipoma, craniopharyngioma, benign neoplasm of brain, benign neoplasm of spinal cord, benign neoplasm of meninges, benign neoplasm of peripheral nervous system, myxoid glioneuronal tumor, diffuse leptomeningeal glioneuronal tumor, polymorphous low grade neuroepithelial tumor of the young

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
MAP2K1	Act	DLBCLNOS,LUAD,MEL,NSCLC,SKCM	CIViC #31

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
MAP2K1	Orphanet:1340	Cardiofaciocutaneous syndrome
MAP2K1	Orphanet:389	Langerhans cell histiocytosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
MAP2K1	HGNC:6840	ENSG00000169032	Q02750	Dual specificity mitogen-activated protein kinase kinase 1	civic_evidence

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.
MAP2K1	Dual specificity mitogen-activated protein kinase kinase 1	Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway.

Protein-family classification

Druggable: 2 · 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
Kinase	2	27.7×	0.001

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
MAP2K1	Kinase	yes	2.7.12.2	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
calcaneal tendon	1
colonic epithelium	1
oocyte	1
orbitofrontal cortex	1
secondary oocyte	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
MAP2K1	298	ubiquitous	marker	secondary oocyte, oocyte, orbitofrontal cortex

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRAF	7,394
MAP2K1	5,944

Intra-cohort edges

A	B	Sources
BRAF	MAP2K1	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRAF	P15056	131
MAP2K1	Q02750	94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 76. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Negative feedback regulation of MAPK pathway	2	1903.3×	2e-05	BRAF, MAP2K1
Prolonged ERK activation events	2	1427.5×	2e-05	BRAF, MAP2K1
Frs2-mediated activation	2	951.7×	3e-05	BRAF, MAP2K1
Signalling to ERKs	2	601.0×	5e-05	BRAF, MAP2K1
Signaling by RAS mutants	2	423.0×	8e-05	BRAF, MAP2K1
RAF activation	2	335.9×	9e-05	BRAF, MAP2K1
Signaling by high-kinase activity BRAF mutants	2	317.2×	9e-05	BRAF, MAP2K1
MAP2K and MAPK activation	2	285.5×	9e-05	BRAF, MAP2K1
Signaling by RAF1 mutants	2	278.5×	9e-05	BRAF, MAP2K1
Negative regulation of MAPK pathway	2	265.6×	9e-05	BRAF, MAP2K1
Signaling by moderate kinase activity BRAF mutants	2	253.8×	9e-05	BRAF, MAP2K1
Paradoxical activation of RAF signaling by kinase inactive BRAF	2	253.8×	9e-05	BRAF, MAP2K1
Signaling downstream of RAS mutants	2	253.8×	9e-05	BRAF, MAP2K1
Oncogenic MAPK signaling	2	248.3×	9e-05	BRAF, MAP2K1
Signaling by NTRK1 (TRKA)	2	196.9×	1e-04	BRAF, MAP2K1
Signaling by NTRKs	2	181.3×	1e-04	BRAF, MAP2K1
Signaling by BRAF and RAF1 fusions	2	170.4×	2e-04	BRAF, MAP2K1
MAPK1/MAPK3 signaling	2	131.3×	2e-04	BRAF, MAP2K1
MAPK family signaling cascades	2	102.9×	4e-04	BRAF, MAP2K1
RAF/MAP kinase cascade	2	61.1×	0.001	BRAF, MAP2K1
Diseases of signal transduction by growth factor receptors and second messengers	2	56.8×	0.001	BRAF, MAP2K1
Signaling by Receptor Tyrosine Kinases	2	51.7×	0.001	BRAF, MAP2K1
Signaling by MAP2K mutants	1	1427.5×	0.002	MAP2K1
Signaling by MRAS-complex mutants	1	1427.5×	0.002	BRAF
Signalling to p38 via RIT and RIN	1	1142.0×	0.003	BRAF
ARMS-mediated activation	1	815.7×	0.004	BRAF
SHOC2 M1731 mutant abolishes MRAS complex function	1	713.8×	0.004	BRAF
Gain-of-function MRAS complexes activate RAF signaling	1	713.8×	0.004	BRAF
Signaling by FGFR3	1	571.0×	0.005	BRAF
MAPK3 (ERK1) activation	1	519.1×	0.005	MAP2K1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
face development	2	802.5×	9e-05	BRAF, MAP2K1
positive regulation of axonogenesis	2	581.1×	9e-05	BRAF, MAP2K1
thyroid gland development	2	543.6×	9e-05	BRAF, MAP2K1
thymus development	2	337.0×	2e-04	BRAF, MAP2K1
ERK1 and ERK2 cascade	2	318.0×	2e-04	BRAF, MAP2K1
MAPK cascade	2	153.2×	6e-04	BRAF, MAP2K1
positive regulation of ERK1 and ERK2 cascade	2	85.1×	0.002	BRAF, MAP2K1
negative regulation of homotypic cell-cell adhesion	1	4213.0×	0.002	MAP2K1
Golgi inheritance	1	4213.0×	0.002	MAP2K1
cerebellar cortex formation	1	2808.7×	0.003	MAP2K1
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	2808.7×	0.003	BRAF
positive regulation of endodermal cell differentiation	1	2808.7×	0.003	MAP2K1
regulation of Golgi inheritance	1	2106.5×	0.003	MAP2K1
regulation of vascular associated smooth muscle contraction	1	1685.2×	0.003	MAP2K1
positive regulation of axon regeneration	1	1685.2×	0.003	BRAF
epithelial cell proliferation involved in lung morphogenesis	1	1685.2×	0.003	MAP2K1
negative regulation of synaptic vesicle exocytosis	1	1685.2×	0.003	BRAF
CD4-positive, alpha-beta T cell differentiation	1	1404.3×	0.003	BRAF
myeloid progenitor cell differentiation	1	1203.7×	0.003	BRAF
positive regulation of muscle contraction	1	1203.7×	0.003	MAP2K1
regulation of axon regeneration	1	1203.7×	0.003	MAP2K1
trachea formation	1	1203.7×	0.003	MAP2K1
positive regulation of D-glucose transmembrane transport	1	1053.2×	0.003	BRAF
head morphogenesis	1	1053.2×	0.003	BRAF
labyrinthine layer development	1	1053.2×	0.003	MAP2K1
negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway	1	1053.2×	0.003	MAP2K1
regulation of early endosome to late endosome transport	1	1053.2×	0.003	MAP2K1
positive regulation of gene expression	2	38.7×	0.003	BRAF, MAP2K1
regulation of stress-activated MAPK cascade	1	936.2×	0.003	MAP2K1
establishment of protein localization to membrane	1	936.2×	0.003	BRAF

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
MAP2K1	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAP2K1	54	4
BRAF	48	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF, MAP2K1
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF, MAP2K1
SORAFENIB	4	BRAF, MAP2K1
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF, MAP2K1
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF, MAP2K1
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, MAP2K1
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
SELUMETINIB	4	MAP2K1
TRAMETINIB	4	MAP2K1
BINIMETINIB	4	MAP2K1
AXITINIB	4	MAP2K1
NERATINIB	4	MAP2K1
TOFACITINIB	4	MAP2K1
VANDETANIB	4	MAP2K1
BOSUTINIB	4	MAP2K1
GILTERITINIB	4	MAP2K1
NINTEDANIB	4	MAP2K1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
MAP2K1	1,200	Binding:1150, Functional:47, ADMET:3

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
MAP2K1	2.7.12.2	mitogen-activated protein kinase kinase

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
MAP2K1	1,200

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
VEMURAFENIB	4	BRAF, MAP2K1
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF, MAP2K1
SORAFENIB	4	BRAF, MAP2K1
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF, MAP2K1
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF, MAP2K1
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF, MAP2K1
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
SELUMETINIB	4	MAP2K1
TRAMETINIB	4	MAP2K1
BINIMETINIB	4	MAP2K1
AXITINIB	4	MAP2K1
NERATINIB	4	MAP2K1
TOFACITINIB	4	MAP2K1
VANDETANIB	4	MAP2K1
BOSUTINIB	4	MAP2K1
GILTERITINIB	4	MAP2K1
NINTEDANIB	4	MAP2K1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BRAF, MAP2K1
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: 0.