Nervous system cancer

Summary

Nervous system cancer (MONDO:0005872) is a cancer (an umbrella term covering 6 Mondo subtypes) with 2 cohort genes (1 GWAS associations across 4 studies; 2 CIViC-evidence somatic drivers; 2 ClinVar predisposition records) and 5 clinical trials. Top therapeutic interventions include gabapentin.

At a glance

• Classification: Cancer
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 2
• GWAS associations: 1
• ClinVar variants: 2
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nervous system cancer
Mondo ID	MONDO:0005872
EFO	EFO:0007392
MeSH	D009423
DOID	DOID:3093
NCIT	C4788
SNOMED CT	372063002
UMLS	C0497549
MedGen	99231
Anatomy (UBERON)	UBERON:0001016
Is cancer (heuristic)	yes

Also known as: cancer of nervous system · malignant neoplasm of nervous system · malignant neoplasm of the nervous system · malignant nervous system neoplasm · malignant nervous system tumor · malignant nervous system tumour · malignant tumor of nervous system · malignant tumor of the nervous system · malignant tumour of nervous system · malignant tumour of the nervous system · nervous system cancer · nervous system neoplasm · nervous system neoplasms, malignant · neural neoplasm · neural tumor · neural tumour · tumor of the nervous system · tumour of the nervous system

Data availability: 2 ClinVar variants · 1 GWAS association (4 studies).

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › nervous system cancer

Related subtypes (32): respiratory system cancer, immune system cancer, musculoskeletal system cancer, integumentary system cancer, peritoneum cancer, cardiovascular cancer, reproductive system cancer, malignant giant cell tumor, digestive system cancer, lipomatous cancer, thoracic cancer, malignant glomus tumor, malignant mesenchymoma, carcinoma, sarcoma, blastoma, head and neck cancer, malignant mixed neoplasm, retroperitoneal cancer, malignant germ cell tumor, malignant mesothelioma, malignant urinary system neoplasm, childhood malignant neoplasm, anaplastic cancer, malignant spindle cell neoplasm, high grade malignant neoplasm, malignant endocrine neoplasm, malignant soft tissue neoplasm, secondary malignant neoplasm, refractory malignant neoplasm, malignant adenoma, cancer of unknown primary site

Subtypes (6): sensory system cancer, central nervous system cancer, ectomesenchymoma, adrenal gland neuroblastoma, cutaneous neuroendocrine carcinoma, peripheral nervous system cancer

Genetics & variants

GWAS landscape

1 GWAS associations across 4 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs114611496	1e-13	IDE	A	2.33

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477218	Verma A	2024	1,417	448,701	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435624	Zhou W	2018	531	407,239	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90479813	Verma A	2024	322	121,279	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481519	Verma A	2024	322	121,279	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs114611496	10	92499682	A>G	0	intron_variant	IDE	1e-13	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
824807	NM_000268.4(NF2):c.433G>A (p.Ala145Thr)	NF2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3723908	NM_003073.5(SMARCB1):c.500G>A (p.Cys167Tyr)	SMARCB1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
SMARCB1	Act	ATRT,MBL,NBL,PANET,PAST	CIViC #5356
NF2	LoF	CCRCC,CESC,HCC,HNSC,MEL,OVT,PAAD,PLMESO,PRCC,RCC	CIViC #3870

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
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMARCB1	HGNC:11103	ENSG00000099956	Q12824	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	clinvar
NF2	HGNC:7773	ENSG00000186575	P35240	Merlin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMARCB1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1	Core component of the BAF (hSWI/SNF) complex.
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: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMARCB1	Other/Unknown	no		SNF5, Sfh1/SNF5, INI1_DNA-bd
NF2	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_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
cortical plate	1
embryo	1
ganglionic eminence	1
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
SMARCB1	214	ubiquitous	marker	embryo, ganglionic eminence, cortical plate
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
SMARCB1	5,083
NF2	3,208

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMARCB1	Q12824	17
NF2	P35240	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. 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×	0.023	SMARCB1
Formation of the polybromo-BAF (pBAF) complex	1	317.2×	0.023	SMARCB1
Formation of the embryonic stem cell BAF (esBAF) complex	1	300.5×	0.023	SMARCB1
RHO GTPases activate PAKs	1	271.9×	0.023	NF2
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	228.4×	0.023	SMARCB1
Regulation of endogenous retroelements	1	184.2×	0.023	SMARCB1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	150.3×	0.023	SMARCB1
Fcgamma receptor (FCGR) dependent phagocytosis	1	139.3×	0.023	NF2
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.023	SMARCB1
Regulation of actin dynamics for phagocytic cup formation	1	92.1×	0.028	NF2
MITF-M-dependent gene expression	1	90.6×	0.028	SMARCB1
RMTs methylate histone arginines	1	73.2×	0.029	SMARCB1
Transcriptional regulation by RUNX1	1	73.2×	0.029	SMARCB1
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	58.9×	0.033	SMARCB1
MITF-M-regulated melanocyte development	1	57.1×	0.033	SMARCB1
Chromatin organization	1	40.8×	0.043	SMARCB1
Chromatin modifying enzymes	1	36.1×	0.043	SMARCB1
Epigenetic regulation of gene expression	1	35.7×	0.043	SMARCB1
RHO GTPase Effectors	1	34.0×	0.043	NF2
Signaling by Rho GTPases	1	17.1×	0.078	NF2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.078	NF2
Innate Immune System	1	12.8×	0.098	NF2
RNA Polymerase II Transcription	1	11.3×	0.106	SMARCB1
Gene expression (Transcription)	1	8.9×	0.127	SMARCB1
Generic Transcription Pathway	1	7.5×	0.143	SMARCB1
Developmental Biology	1	7.2×	0.144	SMARCB1
Immune System	1	6.5×	0.154	NF2
Signal Transduction	1	5.1×	0.187	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cell differentiation	2	267.5×	8e-04	SMARCB1, NF2
single stranded viral RNA replication via double stranded DNA intermediate	1	8426.0×	0.003	SMARCB1
Schwann cell proliferation	1	2808.7×	0.004	NF2
regulation of gliogenesis	1	2808.7×	0.004	NF2
positive regulation of glucose mediated signaling pathway	1	2808.7×	0.004	SMARCB1
RNA polymerase I preinitiation complex assembly	1	1685.2×	0.004	SMARCB1
negative regulation of cell growth involved in contact inhibition	1	1685.2×	0.004	NF2
regulation of organelle assembly	1	1685.2×	0.004	NF2
negative regulation of cell population proliferation	2	42.1×	0.004	SMARCB1, NF2
negative regulation of Schwann cell proliferation	1	1203.7×	0.004	NF2
regulation of hippo signaling	1	1203.7×	0.004	NF2
DNA integration	1	1053.2×	0.004	SMARCB1
regulation of protein localization to nucleus	1	1053.2×	0.004	NF2
positive regulation of early endosome to late endosome transport	1	936.2×	0.004	NF2
positive regulation of protein localization to early endosome	1	842.6×	0.004	NF2
regulation of neural precursor cell proliferation	1	842.6×	0.004	NF2
negative regulation of osteoblast proliferation	1	766.0×	0.004	NF2
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	766.0×	0.004	SMARCB1
osteoblast proliferation	1	702.2×	0.004	NF2
regulation of stem cell proliferation	1	702.2×	0.004	NF2
ectoderm development	1	601.9×	0.004	NF2
hepatocyte differentiation	1	601.9×	0.004	SMARCB1
lens fiber cell differentiation	1	526.6×	0.005	NF2
negative regulation of cell-cell adhesion	1	495.6×	0.005	NF2
negative regulation of cell-matrix adhesion	1	443.5×	0.005	NF2
host-mediated activation of viral transcription	1	443.5×	0.005	SMARCB1
negative regulation of receptor signaling pathway via JAK-STAT	1	443.5×	0.005	NF2
nucleosome disassembly	1	401.2×	0.005	SMARCB1
hippo signaling	1	366.4×	0.005	NF2
regulation of G0 to G1 transition	1	337.0×	0.006	SMARCB1

Therapeutics

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
SMARCB1	0	0
NF2	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).

Drug repurposing candidates

0 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.

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	SMARCB1, NF2

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)
SMARCB1	7	—
NF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03911388	PHASE1	RECRUITING	HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
NCT07606287	Not specified	NOT_YET_RECRUITING	Studying the Workflow of the American College of Surgeons Geriatric Surgery Program to Improve Clinical Outcomes in Older Adults Undergoing Surgery at the James Cancer Hospital
NCT00340496	Not specified	COMPLETED	Analysis of NF2 Mutations in Radiation-Related Neural Tumors
NCT01236053	Not specified	COMPLETED	Cancer in Patients With Gabapentin (GPRD)
NCT01798771	Not specified	UNKNOWN	Intraoperative MRI and 5-ALA Guidance to Improve the Extent of Resection in Brain Tumor Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GABAPENTIN	4	1