Acoustic neuroma

Summary

Acoustic neuroma (MONDO:0001569) is a disease with 1 cohort gene and 77 clinical trials. Top therapeutic interventions include gentamicin, lapatinib, and axitinib.

At a glance

• Prevalence: 1-9 / 100 000 (Denmark) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Clinical trials: 77

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	2	Denmark	Validated
Annual incidence	1-9 / 100 000	1.2	United States	Validated
Annual incidence	1-9 / 1 000 000	0.8	Specific population	Validated
Annual incidence	1-9 / 100 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	acoustic neuroma
Mondo ID	MONDO:0001569
MeSH	D009464
Orphanet	252175
DOID	DOID:12689
ICD-11	480288993
NCIT	C3276
SNOMED CT	126949007
UMLS	C0027859
MedGen	45062
GARD	0000223
MedDRA	10000523
NORD	715
Is cancer (heuristic)	no

Also known as: acoustic neurilemmoma · acoustic neurilemoma · acoustic neurinoma · acoustic neuroma · acoustic schwannoma · acoustic tumor · acoustic tumour · neurilemoma, acoustic · neurinoma of the acoustic nerve · neuroma, acoustic · vestibular neurilemmoma · vestibular schwannoma · vestibular schwannoma (disease)

Data availability: 3 ClinVar variants · 1 HPO phenotype · 6 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral nervous system neoplasm › nerve sheath neoplasm › schwannoma › acoustic neuroma

Related subtypes (9): cellular schwannoma, schwannoma of twelfth cranial nerve, sympathetic neurilemmoma, trigeminal schwannoma, microcystic/reticular schwannoma, melanotic neurilemmoma, plexiform schwannoma, peripheral nerve schwannoma, schwannomatosis

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3283	NM_000268.4(NF2):c.240+1G>T	NF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4280296	NM_000268.4(NF2):c.810G>A (p.Glu270=)	NF2	Likely pathogenic	criteria provided, single submitter
3297	NM_000268.4(NF2):c.185T>C (p.Phe62Ser)	NF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
NF2	Orphanet:2495	Meningioma
NF2	Orphanet:634475	Mosaic NF2-related schwannomatosis
NF2	Orphanet:637	Full NF2-related schwannomatosis
NF2	Orphanet:93921	Full schwannomatosis

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
NF2	HGNC:7773	ENSG00000186575	P35240	Merlin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NF2	Merlin	Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis.

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)
NF2	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_sf

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
dorsal motor nucleus of vagus nerve	1
endometrium epithelium	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NF2	283	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, dorsal motor nucleus of vagus nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF2	3,208

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NF2	P35240	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
RHO GTPases activate PAKs	1	543.8×	0.016	NF2
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.016	NF2
Regulation of actin dynamics for phagocytic cup formation	1	184.2×	0.016	NF2
RHO GTPase Effectors	1	68.0×	0.033	NF2
Signaling by Rho GTPases	1	34.2×	0.045	NF2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.045	NF2
Innate Immune System	1	25.5×	0.050	NF2
Immune System	1	13.0×	0.087	NF2
Signal Transduction	1	10.2×	0.098	NF2

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
Schwann cell proliferation	1	5617.3×	0.002	NF2
regulation of gliogenesis	1	5617.3×	0.002	NF2
negative regulation of cell growth involved in contact inhibition	1	3370.4×	0.002	NF2
regulation of organelle assembly	1	3370.4×	0.002	NF2
negative regulation of Schwann cell proliferation	1	2407.4×	0.002	NF2
regulation of hippo signaling	1	2407.4×	0.002	NF2
regulation of protein localization to nucleus	1	2106.5×	0.002	NF2
positive regulation of early endosome to late endosome transport	1	1872.4×	0.002	NF2
positive regulation of protein localization to early endosome	1	1685.2×	0.002	NF2
regulation of neural precursor cell proliferation	1	1685.2×	0.002	NF2
negative regulation of osteoblast proliferation	1	1532.0×	0.002	NF2
osteoblast proliferation	1	1404.3×	0.002	NF2
regulation of stem cell proliferation	1	1404.3×	0.002	NF2
ectoderm development	1	1203.7×	0.002	NF2
lens fiber cell differentiation	1	1053.2×	0.002	NF2
negative regulation of cell-cell adhesion	1	991.3×	0.002	NF2
negative regulation of cell-matrix adhesion	1	887.0×	0.002	NF2
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.002	NF2
hippo signaling	1	732.7×	0.002	NF2
cell-cell junction organization	1	624.1×	0.003	NF2
mesoderm formation	1	495.6×	0.003	NF2
positive regulation of stress fiber assembly	1	312.1×	0.005	NF2
odontogenesis of dentin-containing tooth	1	300.9×	0.005	NF2
negative regulation of MAPK cascade	1	300.9×	0.005	NF2
positive regulation of cell differentiation	1	267.5×	0.005	NF2
hippocampus development	1	230.8×	0.006	NF2
MAPK cascade	1	153.2×	0.008	NF2
regulation of protein stability	1	125.8×	0.010	NF2
regulation of cell shape	1	123.0×	0.010	NF2
negative regulation of cell migration	1	111.6×	0.010	NF2

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Losartan, Nilotinib, Nimodipine.

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NF2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NF2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 77.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	50
PHASE2	15
EARLY_PHASE1	4
PHASE1	3
PHASE4	2
PHASE3	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02379754	PHASE4	WITHDRAWN	Gentamicin Treatment Prior to Schwannoma Surgery - Residual Function
NCT02415257	PHASE4	WITHDRAWN	Gentamicin Treatment Prior to Schwannoma Surgery - No Residual Function
NCT07116811	PHASE3	NOT_YET_RECRUITING	Steroids for Facial Nerve Function Protection in Post-surgical Vestibular Schwannoma Patients
NCT01449604	PHASE3	UNKNOWN	Stereotactic Radiation in Vestibular Schwannoma
NCT01199978	PHASE2	ACTIVE_NOT_RECRUITING	Hearing Outcomes Using Fractionated Proton Radiation Therapy for Vestibular Schwannoma
NCT03079999	PHASE2	ACTIVE_NOT_RECRUITING	Study of Aspirin in Patients With Vestibular Schwannoma
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT06517888	PHASE1/PHASE2	RECRUITING	Anti-VEGF Gene Therapy Trial for Vestibular Schwannoma
NCT00973739	PHASE2	COMPLETED	Lapatinib Study for Children and Adults With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
NCT01125046	PHASE2	COMPLETED	Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas
NCT01207687	PHASE2	COMPLETED	Bevacizumab for Symptomatic Vestibular Schwannoma in Neurofibromatosis Type 2 (NF2)
NCT01345136	PHASE2	TERMINATED	Study of RAD001 for Treatment of NF2-related Vestibular Schwannoma
NCT02104323	PHASE2	COMPLETED	Endostatin Study for Patients With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
NCT02129647	PHASE2	COMPLETED	Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
NCT02934256	PHASE2	COMPLETED	Icotinib Study for Patients With Neurofibromatosis Type 2 (NF2) and NF2-Related Tumors
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03393689	PHASE2	UNKNOWN	RGD PET/MRI in Sporadic Vestibular Schwannoma
NCT04351373	PHASE2	COMPLETED	Microscopic Fluorescence-guided Vestibular Schwannoma Resection Using Fluorescein Sodium and YELLOW 560
NCT04801953	PHASE2	UNKNOWN	Nimodipine in Vestibular Schwanommas
NCT06322342	PHASE2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT01083966	PHASE1	SUSPENDED	Super-Selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Vestibular Schwannoma
NCT01119599	PHASE1	COMPLETED	RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma
NCT04658836	PHASE1	COMPLETED	Triamcinolone Levels in Cochlear Perilymph, Lateral Canal and CSF
NCT07493447	EARLY_PHASE1	NOT_YET_RECRUITING	Pilot Study Evaluating Panitumumab-IRDye800 as an Optical Imaging Agent to Detect Intracranial Lesions During Neurosurgical Procedures
NCT00863122	EARLY_PHASE1	COMPLETED	Concentration and Activity of Lapatinib in Vestibular Schwannomas
NCT01880749	EARLY_PHASE1	COMPLETED	Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
NCT02282917	EARLY_PHASE1	TERMINATED	Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma
NCT03346889	Not specified	ACTIVE_NOT_RECRUITING	Vestibular Outcomes in Vestibular Schwannoma
NCT03745534	Not specified	RECRUITING	Cochlear Implantation After Gamma Knife Radiosurgery with EABR and Correlation to Postoperative Hearing Results - a Pilot Study
NCT03745560	Not specified	RECRUITING	Intraoperative EABR for Decision Making
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04859335	Not specified	RECRUITING	Evolution of Balance and Vestibular Function in Patients Treated With Gammaknife Radiosurgery for Vestibular Schwannoma
NCT05622344	Not specified	RECRUITING	StableEyes With Active Neurofeedback
NCT05641441	Not specified	RECRUITING	Radiosurgery Induced Ototoxicity in Patients Treated for a Vestibular Schwannoma
NCT05702749	Not specified	RECRUITING	Evaluating Pre-Treatment Vestibular Physical Therapy Rehab for Patients With Vestibular Schwannomas
NCT06112509	Not specified	RECRUITING	Evolution of Vestibular Function After Treatment of a Vestibular Schwannoma by Gamma-knife Radio-surgery
NCT06572475	Not specified	RECRUITING	USPIO Enhanced MR Imaging in CNS Tumours (UMIC)
NCT06660082	Not specified	RECRUITING	Early Rehabilitation Using Head Impulse Test for Acute Vestibular Deficit
NCT06844461	Not specified	RECRUITING	Quality of Life and Decisional Regret in Patients Affected by Acoustic Neuroma
NCT07130851	Not specified	ACTIVE_NOT_RECRUITING	Mapping of Vestibular Centers Activation Using fMRI in Patients With Vestibular Schwannoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GENTAMICIN	4	2
LAPATINIB	4	2
AXITINIB	4	1
BRIGATINIB	4	1
EDOTREOTIDE GALLIUM GA-68	4	1
FLUORESCEIN SODIUM	4	1
NERATINIB	4	1
RETIFANLIMAB	4	1
SELUMETINIB	4	1
ENDOSTATIN	3	1
ICOTINIB	3	1
AR-42	2	1
ISOXAFLUTOLE	2	1
CHEMBL195892	0	2
CHEMBL3039597	0	2
GENTAMICIN C1A	0	2
GENTAMICIN C2	0	2
CHEMBL3939307	0	1
CHEMBL4463209	0	1
CHEMBL1200433	0	1
CHEMBL3397300	0	1