Schwannoma

Summary

Schwannoma (MONDO:0002546) is a disease (an umbrella term covering 10 Mondo subtypes) with 2 cohort genes and 16 clinical trials. Top therapeutic interventions include erenumab, piflufolastat f18, and siltuximab.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 10 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 25
• Clinical trials: 16

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	6	Europe	Validated

Signs & symptoms

Clinical features (HPO)

25 HPO clinical features (Orphanet curated; top 25 by frequency):

HPO ID	Term	Frequency
HP:0001291	Abnormal cranial nerve morphology	Very frequent (80-99%)
HP:0009588	Vestibular schwannoma	Very frequent (80-99%)
HP:0009593	Peripheral schwannoma	Very frequent (80-99%)
HP:0009911	Abnormal temporal bone morphology	Very frequent (80-99%)
HP:0030177	Abnormality of peripheral nervous system electrophysiology	Very frequent (80-99%)
HP:0100008	Schwannoma	Very frequent (80-99%)
HP:0100011	Scleral schwannoma	Very frequent (80-99%)
HP:0000364	Hearing abnormality	Frequent (30-79%)
HP:0002321	Vertigo	Frequent (30-79%)
HP:0010628	Facial palsy	Frequent (30-79%)
HP:0012533	Allodynia	Frequent (30-79%)
HP:0000197	Abnormal parotid gland morphology	Occasional (5-29%)
HP:0000769	Abnormality of the breast	Occasional (5-29%)
HP:0000834	Abnormality of the adrenal glands	Occasional (5-29%)
HP:0001392	Abnormality of the liver	Occasional (5-29%)
HP:0001600	Abnormality of the larynx	Occasional (5-29%)
HP:0002011	Morphological central nervous system abnormality	Occasional (5-29%)
HP:0002031	Abnormal esophagus morphology	Occasional (5-29%)
HP:0002991	Abnormal fibula morphology	Occasional (5-29%)
HP:0003489	Acute episodes of neuropathic symptoms	Occasional (5-29%)
HP:0010826	Abnormality of the twelfth cranial nerve	Occasional (5-29%)
HP:0012531	Pain	Occasional (5-29%)
HP:0100582	Nasal polyposis	Occasional (5-29%)
HP:0200008	Intestinal polyposis	Occasional (5-29%)
HP:0100697	Neurofibrosarcoma	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	schwannoma
Mondo ID	MONDO:0002546
EFO	EFO:0000693
Orphanet	252164
DOID	DOID:3192, DOID:955
ICD-11	378766741
NCIT	C3269
SNOMED CT	404022001
UMLS	C0027809
MedGen	45053
GARD	0004767
MedDRA	10029234, 10029235
Is cancer (heuristic)	no

Also known as: benign neurilemmoma · benign schwannoma · neurilemmoma · neurinoma · neurolemmoma · peripheral fibroblastoma · SCHW · schwannoma · schwannoma (WHO grade I) · schwannoma, benign

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record · 4 cell lines.

Disease family

An umbrella term covering 10 Mondo subtypes.

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

Related subtypes (5): granular cell tumor, neurothekeoma, neurofibroma, malignant peripheral nerve sheath tumor, perineurioma

Subtypes (10): acoustic neuroma, 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
239481	NM_003073.5(SMARCB1):c.*82C>T	SMARCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DGCR8	Limited	Autosomal dominant	schwannoma

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCB1	Orphanet:1465	Coffin-Siris syndrome
SMARCB1	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCB1	Orphanet:2495	Meningioma
SMARCB1	Orphanet:263662	Familial multiple meningioma
SMARCB1	Orphanet:93921	Full schwannomatosis
SMARCB1	Orphanet:99966	Atypical teratoid rhabdoid tumor

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DGCR8	HGNC:2847	ENSG00000128191	Q8WYQ5	Microprocessor complex subunit DGCR8	gencc
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DGCR8	Microprocessor complex subunit DGCR8	Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis.
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DGCR8	Scaffold/PPI	no		WW_dom, dsRBD_dom, WW_dom_sf
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
cortical plate	1
embryo	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DGCR8	271	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMARCB1	5,083
DGCR8	2,752

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17
DGCR8	Q8WYQ5	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Formation of the canonical BAF (cBAF) complex	1	317.2×	0.017	SMARCB1
Formation of the polybromo-BAF (pBAF) complex	1	317.2×	0.017	SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	1	300.5×	0.017	SMARCB1
MicroRNA (miRNA) biogenesis	1	228.4×	0.017	DGCR8
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	228.4×	0.017	SMARCB1
Regulation of endogenous retroelements	1	184.2×	0.017	SMARCB1
Transcriptional Regulation by MECP2	1	158.6×	0.017	DGCR8
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.017	SMARCB1
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.018	SMARCB1
MITF-M-dependent gene expression	1	90.6×	0.023	SMARCB1
RMTs methylate histone arginines	1	73.2×	0.024	SMARCB1
Transcriptional regulation by RUNX1	1	73.2×	0.024	SMARCB1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	58.9×	0.026	SMARCB1
MITF-M-regulated melanocyte development	1	57.1×	0.026	SMARCB1
Chromatin organization	1	40.8×	0.034	SMARCB1
Chromatin modifying enzymes	1	36.1×	0.034	SMARCB1
Epigenetic regulation of gene expression	1	35.7×	0.034	SMARCB1
RNA Polymerase II Transcription	1	11.3×	0.101	SMARCB1
Gene expression (Transcription)	1	8.9×	0.120	SMARCB1
Generic Transcription Pathway	1	7.5×	0.134	SMARCB1
Developmental Biology	1	7.2×	0.134	SMARCB1

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
single stranded viral RNA replication via double stranded DNA intermediate	1	8426.0×	0.003	SMARCB1
positive regulation of pre-miRNA processing	1	4213.0×	0.003	DGCR8
positive regulation of glucose mediated signaling pathway	1	2808.7×	0.003	SMARCB1
RNA polymerase I preinitiation complex assembly	1	1685.2×	0.004	SMARCB1
DNA integration	1	1053.2×	0.005	SMARCB1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	766.0×	0.005	SMARCB1
regulation of stem cell proliferation	1	702.2×	0.005	DGCR8
primary miRNA processing	1	648.1×	0.005	DGCR8
hepatocyte differentiation	1	601.9×	0.005	SMARCB1
host-mediated activation of viral transcription	1	443.5×	0.006	SMARCB1
nucleosome disassembly	1	401.2×	0.006	SMARCB1
regulation of G0 to G1 transition	1	337.0×	0.007	SMARCB1
regulation of nucleotide-excision repair	1	300.9×	0.007	SMARCB1
blastocyst hatching	1	271.8×	0.007	SMARCB1
regulation of mitotic metaphase/anaphase transition	1	247.8×	0.008	SMARCB1
positive regulation of T cell differentiation	1	227.7×	0.008	SMARCB1
transcription initiation-coupled chromatin remodeling	1	191.5×	0.008	SMARCB1
positive regulation of myoblast differentiation	1	183.2×	0.008	SMARCB1
positive regulation of stem cell population maintenance	1	172.0×	0.008	SMARCB1
positive regulation of double-strand break repair	1	172.0×	0.008	SMARCB1
regulation of G1/S transition of mitotic cell cycle	1	153.2×	0.009	SMARCB1
positive regulation of cell differentiation	1	133.8×	0.009	SMARCB1
chromatin remodeling	1	36.5×	0.033	SMARCB1
DNA damage response	1	26.8×	0.043	DGCR8
nervous system development	1	23.0×	0.048	SMARCB1
negative regulation of cell population proliferation	1	21.1×	0.051	SMARCB1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.135	SMARCB1
regulation of transcription by RNA polymerase II	1	5.8×	0.164	SMARCB1

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.

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DGCR8	0	0
SMARCB1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMARCB1	7	Binding:7

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).

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	2	DGCR8, SMARCB1

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)
DGCR8	0	—
SMARCB1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 16.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	13
PHASE2	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05684692	PHASE2	RECRUITING	Screening Trial for Pain Relief in Schwannomatosis (STARFISH)
NCT06322342	PHASE2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT03542773	PHASE1	COMPLETED	Targeted Imaging of Glutamate Carboxypeptidase II With DCFPyL-PET
NCT04278118	Not specified	RECRUITING	Hypofractionated Proton Therapy for Benign Intracranial Brain Tumors, the HiPPI Study
NCT04648462	Not specified	RECRUITING	Proton Therapy Research Infrastructure- ProTRAIT- Neuro-oncology
NCT05139277	Not specified	RECRUITING	Evaluation of the CONVIVO System
NCT05254197	Not specified	RECRUITING	SeOuL cOhort of Brain Tumor MONitoring Study (SOLOMON)
NCT05576103	Not specified	RECRUITING	Longitudinal Prospective Study of Neurocognition & Neuroimaging in Primary BT Patients
NCT06421805	Not specified	RECRUITING	Establishing Prospective Mediastinal Tumor Database of PUMCH
NCT07078136	Not specified	RECRUITING	Multicenter Observational Study of Multimodal AI for Upper GI Mesenchymal Tumor Diagnosis
NCT00603694	Not specified	COMPLETED	Hippocampal Radiation Exposure and Memory
NCT01347307	Not specified	COMPLETED	Stereotactic Body Radiotherapy for Spine Tumors
NCT01951365	Not specified	COMPLETED	Assessment of Volumetric Growth Rates of Spinal Intradural Extramedullary Schwannoma
NCT03580850	Not specified	UNKNOWN	MRI Scan and Intra-labyrinthine Schwannoma
NCT04417868	Not specified	UNKNOWN	Evolution of Cochleovestibular Schwannomas
NCT04712214	Not specified	UNKNOWN	Use of Non-invasive Optical Analysis in Neurosurgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ERENUMAB	4	1
PIFLUFOLASTAT F18	4	1
SILTUXIMAB	4	1