Meningioma

Summary

Meningioma (MONDO:0016642) is a disease (an umbrella term covering 37 Mondo subtypes) with 11 cohort genes (4 GWAS associations across 6 studies) and 127 clinical trials. Top therapeutic interventions include lutetium oxodotreotide lu-177, edotreotide gallium ga-68, and tranexamic acid.

At a glance

• Prevalence: Unknown (Europe) [Orphanet-validated]
• Umbrella term: 37 Mondo subtypes
• Cohort genes: 11
• GWAS associations: 4
• ClinVar variants: 9
• Phenotypes (HPO): 74
• Clinical trials: 127

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	4.15	Germany	Validated
Annual incidence	1-9 / 100 000	8.14	United States	Validated

Signs & symptoms

Clinical features (HPO)

74 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0010997	Chromosomal breakage induced by ionizing radiation	Very frequent (80-99%)
HP:0011133	Increased sensitivity to ionizing radiation	Very frequent (80-99%)
HP:0100009	Intracranial meningioma	Very frequent (80-99%)
HP:0000044	Hypogonadotropic hypogonadism	Frequent (30-79%)
HP:0000141	Amenorrhea	Frequent (30-79%)
HP:0000802	Impotence	Frequent (30-79%)
HP:0000870	Increased circulating prolactin concentration	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002920	Decreased circulating ACTH level	Frequent (30-79%)
HP:0007359	Focal-onset seizure	Frequent (30-79%)
HP:0008163	Decreased circulating cortisol level	Frequent (30-79%)
HP:0008214	Decreased serum estradiol	Frequent (30-79%)
HP:0008240	Secondary growth hormone deficiency	Frequent (30-79%)
HP:0008245	Pituitary hypothyroidism	Frequent (30-79%)
HP:0012658	Abnormal brain FDG positron emission tomography	Frequent (30-79%)
HP:0012691	Focal T2 hypointense thalamic lesion	Frequent (30-79%)
HP:0030341	Decreased circulating follicle stimulating hormone concentration	Frequent (30-79%)
HP:0030344	Decreased circulating luteinizing hormone level	Frequent (30-79%)
HP:0030521	Bitemporal hemianopia	Frequent (30-79%)
HP:0040171	Decreased serum testosterone concentration	Frequent (30-79%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000602	Ophthalmoplegia	Occasional (5-29%)
HP:0001067	Neurofibromas	Occasional (5-29%)
HP:0001085	Papilledema	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001269	Hemiparesis	Occasional (5-29%)
HP:0001317	Abnormal cerebellum morphology	Occasional (5-29%)
HP:0001513	Obesity	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0002516	Increased intracranial pressure	Occasional (5-29%)
HP:0003484	Upper limb muscle weakness	Occasional (5-29%)
HP:0004302	Functional motor deficit	Occasional (5-29%)
HP:0004408	Abnormality of the sense of smell	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0007340	Lower limb muscle weakness	Occasional (5-29%)
HP:0007715	Weak extraocular muscles	Occasional (5-29%)
HP:0007924	Slow decrease in visual acuity	Occasional (5-29%)
HP:0008202	Reduced circulating prolactin concentration	Occasional (5-29%)
HP:0008237	Hypothalamic hypothyroidism	Occasional (5-29%)
HP:0010628	Facial palsy	Occasional (5-29%)
HP:0011442	Abnormality of central motor function	Occasional (5-29%)
HP:0011730	Abnormality of central sensory function	Occasional (5-29%)
HP:0011750	Neoplasm of the anterior pituitary	Occasional (5-29%)
HP:0012246	Oculomotor nerve palsy	Occasional (5-29%)
HP:0012285	Abnormal hypothalamus physiology	Occasional (5-29%)
HP:0012505	Enlarged pituitary gland	Occasional (5-29%)
HP:0030532	Visual acuity test abnormality	Occasional (5-29%)
HP:0030591	Abnormal kinetic perimetry test	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	meningioma
Mondo ID	MONDO:0016642
MeSH	D008579
Orphanet	2495
DOID	DOID:3565
ICD-11	672106711
NCIT	C3230
SNOMED CT	302820008
UMLS	C0025286
MedGen	7532
GARD	0007015
MedDRA	10027191
NORD	1434
Is cancer (heuristic)	no

Also known as: meningioma · meningioma (disease) · meningothelial cell tumour · primary meningeal tumour

Data availability: 9 ClinVar variants · 4 GWAS associations (6 studies) · 1 GenCC gene-disease record · 1 HPO phenotype · 38 cell lines.

Disease family

An umbrella term covering 37 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › central nervous system neoplasm › tumor of meninges › meningioma

Related subtypes (4): diffuse leptomeningeal melanocytosis, familial multiple meningioma, malignant tumor of meninges, benign neoplasm of meninges

Subtypes (37): intraspinal meningioma, intraventricular meningioma, intraorbital meningioma, clear cell meningioma, posterior cranial fossa meningioma, anterior cranial fossa meningioma, skull base meningioma, benign meningioma, secretory meningioma, lymphoplasmacyte-rich meningioma, pediatric meningioma, microcystic meningioma, middle cranial fossa meningioma, rhabdoid meningioma, optic nerve sheath meningioma, lung meningioma, malignant leptomeningeal tumor, jugular foramen meningioma, angiomatous meningioma, psammomatous meningioma, fibrous meningioma, meningothelial meningioma, transitional meningioma, petrous apex meningioma, gasserian ganglion meningioma, skin meningioma, periocular meningioma, pineal region meningioma, parapharyngeal meningioma, radiation-induced meningioma, familial meningioma, grade III meningioma, papillary meningioma, optic tract meningioma, grade II meningioma, intracranial meningioma, supratentorial meningioma

Genetics & variants

GWAS landscape

4 GWAS associations across 6 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11012732	2e-14	MLLT10	A	1.46
rs2686876	1e-08	COX8BP - NLRP6	T	1.44
rs141887933	5e-08	GREB1	T	3.98
rs35127183	7e-07	SEC11A	A	1.63

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST005870	Claus EB	2018	1,606	9,823	Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.
GCST001184	Dobbins SE	2011	859	0	Common variation at 10p12.31 near MLLT10 influences meningioma risk.
GCST90446239	Yamada S	2024	401	50,876	Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.
GCST90446242	Yamada S	2024	302	24,409	Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.
GCST90446241	Yamada S	2024	244	50,876	Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.
GCST90446240	Yamada S	2024	151	50,876	Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.

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	4

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	4

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11012732	10	21541175	A>G	0.32	intron_variant	MLLT10	2e-14	Tier 4: intronic/intergenic
rs2686876	11	258909	T>A,C	0.09	intron_variant	COX8BP - NLRP6	1e-08	Tier 4: intronic/intergenic
rs141887933	2	11579990	G>T	0.011	intron_variant	GREB1	5e-08	Tier 4: intronic/intergenic
rs35127183	15	84672508	G>A	0.11	intron_variant	SEC11A	7e-07	Tier 4: intronic/intergenic

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

3 pathogenic, 3 uncertain significance, 2 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3284	NM_000268.4(NF2):c.995del (p.Lys332fs)	NF2	Pathogenic	no assertion criteria provided
3285	NM_000268.4(NF2):c.169C>T (p.Arg57Ter)	NF2	Pathogenic	criteria provided, multiple submitters, no conflicts
12598	NM_002608.4(PDGFB):c.602-1396_602-1262del	PDGFB	Pathogenic	no assertion criteria provided
298574	NM_016169.4(SUFU):c.910+14C>T	SUFU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2135982	NM_000268.4(NF2):c.1593G>C (p.Lys531Asn)	NF2	Uncertain significance	criteria provided, multiple submitters, no conflicts
7840	NM_000314.8(PTEN):c.701G>A (p.Arg234Gln)	PTEN	Uncertain significance	reviewed by expert panel
142405	NM_005732.4(RAD50):c.1378G>A (p.Val460Met)	RAD50	Uncertain significance	criteria provided, multiple submitters, no conflicts
341070	NM_000268.4(NF2):c.886-15C>T	NF2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
239493	NM_003079.5(SMARCE1):c.351C>T (p.Asn117=)	SMARCE1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 37 · 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
NTHL1	Limited	Autosomal recessive	meningioma	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LEPR	Orphanet:179494	Obesity due to leptin receptor gene deficiency
NTHL1	Orphanet:454840	NTHL1-related polyposis
SMARCE1	Orphanet:1465	Coffin-Siris syndrome
SMARCE1	Orphanet:2495	Meningioma
SMARCE1	Orphanet:263662	Familial multiple meningioma
MLLT10	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
SUFU	Orphanet:2495	Meningioma
SUFU	Orphanet:251858	Medulloblastoma with extensive nodularity
SUFU	Orphanet:251863	Desmoplastic/nodular medulloblastoma
SUFU	Orphanet:263662	Familial multiple meningioma
SUFU	Orphanet:280200	Microform holoprosencephaly
SUFU	Orphanet:377	Gorlin syndrome
SUFU	Orphanet:475	Isolated Joubert syndrome
NF2	Orphanet:2495	Meningioma
NF2	Orphanet:634475	Mosaic NF2-related schwannomatosis
NF2	Orphanet:637	Full NF2-related schwannomatosis
NF2	Orphanet:93921	Full schwannomatosis
PDGFB	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFB	Orphanet:2495	Meningioma
PDGFB	Orphanet:263662	Familial multiple meningioma
PDGFB	Orphanet:31112	Dermatofibrosarcoma protuberans
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy
RAD50	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD50	Orphanet:240760	Nijmegen breakage syndrome-like disorder

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2
civic_only	2
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LEPR	HGNC:6554	ENSG00000116678	P48357	Leptin receptor	civic_evidence
NTHL1	HGNC:8028	ENSG00000065057	P78549	Endonuclease III-like protein 1	gencc
PTTG1	HGNC:9690	ENSG00000164611	O95997	Securin	civic_evidence
SMARCE1	HGNC:11109	ENSG00000073584	Q969G3	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1	clinvar
MLLT10	HGNC:16063	ENSG00000078403	P55197	Protein AF-10	gwas
SUFU	HGNC:16466	ENSG00000107882	Q9UMX1	Suppressor of fused homolog	clinvar
RIC8A	HGNC:29550	ENSG00000177963	Q9NPQ8	Chaperone Ric-8A	gwas
NF2	HGNC:7773	ENSG00000186575	P35240	Merlin	clinvar
PDGFB	HGNC:8800	ENSG00000100311	P01127	Platelet-derived growth factor subunit B	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar
RAD50	HGNC:9816	ENSG00000113522	Q92878	DNA repair protein RAD50	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LEPR	Leptin receptor	Receptor for hormone LEP/leptin.
NTHL1	Endonuclease III-like protein 1	Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage.
PTTG1	Securin	Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair.
SMARCE1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
MLLT10	Protein AF-10	Probably involved in transcriptional regulation.
SUFU	Suppressor of fused homolog	Negative regulator in the hedgehog/smoothened signaling pathway.
RIC8A	Chaperone Ric-8A	Chaperone that specifically binds and folds nascent G alpha proteins prior to G protein heterotrimer formation, promoting their stability and activity: folds GNAI1, GNAO1, GNA13 and GNAQ.
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.
PDGFB	Platelet-derived growth factor subunit B	Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
RAD50	DNA repair protein RAD50	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 7 · Druggable fraction: 0.27

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
Phosphatase	1	7.6×	0.618
Antibody/Immunoglobulin	1	2.6×	0.698
Other/Unknown	7	1.1×	0.698
Enzyme (other)	1	1.1×	0.758
Transcription factor	1	0.8×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LEPR	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, Hempt_rcpt_S_F1_CS, FN3_dom
NTHL1	Enzyme (other)	yes	4.2.99.18	HhH_motif, HhH-GPD_domain, Endonuclease3_FeS-loop_motif
PTTG1	Other/Unknown	no		Securin_separation_inhibitor
SMARCE1	Other/Unknown	no		HMG_box_dom, HMG_box_dom_sf
MLLT10	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
SUFU	Other/Unknown	no		Suppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
RIC8A	Other/Unknown	no		Chaperone_Ric-8_A/B, ARM-like, ARM-type_fold
NF2	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_sf
PDGFB	Other/Unknown	no		PDGF/VEGF_dom, PDGF_N, PD_growth_factor_CS
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
RAD50	Other/Unknown	no		Rad50_eukaryotes, Zn_hook_RAD50, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

10 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)	11
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	3
apex of heart	2
ventricular zone	2
colonic epithelium	2
stromal cell of endometrium	2
choroid plexus epithelium	1
trabecular bone tissue	1
trigeminal ganglion	1
mucosa of transverse colon	1
right lobe of liver	1
oocyte	1
secondary oocyte	1
embryo	1
ganglionic eminence	1
adult organism	1
buccal mucosa cell	1
kidney epithelium	1
upper arm skin	1
vena cava	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LEPR	272	broad	marker	trabecular bone tissue, choroid plexus epithelium, trigeminal ganglion
NTHL1	211	ubiquitous	marker	right lobe of liver, apex of heart, mucosa of transverse colon
PTTG1	246	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
SMARCE1	197	ubiquitous	marker	calcaneal tendon, embryo, ganglionic eminence
MLLT10	275	ubiquitous	marker	buccal mucosa cell, adult organism, colonic epithelium
SUFU	226	ubiquitous	yes	upper arm skin, kidney epithelium, vena cava
RIC8A	274	ubiquitous	marker	stromal cell of endometrium, ventricular zone, granulocyte
NF2	283	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, dorsal motor nucleus of vagus nerve
PDGFB	259	ubiquitous	marker	olfactory bulb, type B pancreatic cell, apex of heart
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
RAD50	134	ubiquitous	marker	corpus callosum, calcaneal tendon, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTEN	11,626
NF2	3,208
SMARCE1	2,977
RAD50	2,552
PDGFB	2,424
LEPR	2,243
PTTG1	2,225
SUFU	2,188
NTHL1	1,994
RIC8A	1,436

Structural data

PDB: 10 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTEN	P60484	12
SUFU	Q9UMX1	10
LEPR	P48357	9
SMARCE1	Q969G3	8
MLLT10	P55197	6
NF2	P35240	6
PDGFB	P01127	6
RAD50	Q92878	6
NTHL1	P78549	2
PTTG1	O95997	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RIC8A	Q9NPQ8	90.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 85. Enrichment computed across 11 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective NTHL1 substrate processing	1	1268.9×	0.033	NTHL1
Defective NTHL1 substrate binding	1	1268.9×	0.033	NTHL1
PTEN Loss of Function in Cancer	1	634.4×	0.045	PTEN
Sensing of DNA Double Strand Breaks	1	211.5×	0.086	RAD50
Regulation of PTEN mRNA translation	1	126.9×	0.086	PTEN
Displacement of DNA glycosylase by APEX1	1	115.3×	0.086	NTHL1
Signaling by Leptin	1	115.3×	0.086	LEPR
Regulation of PTEN localization	1	115.3×	0.086	PTEN
HDR through MMEJ (alt-NHEJ)	1	97.6×	0.086	RAD50
Formation of the canonical BAF (cBAF) complex	1	70.5×	0.086	SMARCE1
Formation of the polybromo-BAF (pBAF) complex	1	70.5×	0.086	SMARCE1
Formation of the embryonic stem cell BAF (esBAF) complex	1	66.8×	0.086	SMARCE1
RHO GTPases activate PAKs	1	60.4×	0.086	NF2
Impaired BRCA2 binding to PALB2	1	50.8×	0.086	RAD50
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	50.8×	0.086	SMARCE1
Synthesis of IP3 and IP4 in the cytosol	1	47.0×	0.086	PTEN
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	47.0×	0.086	RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	47.0×	0.086	RAD50
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	47.0×	0.086	RAD50
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	43.8×	0.086	RAD50
Downstream signal transduction	1	42.3×	0.086	PDGFB
Homologous DNA Pairing and Strand Exchange	1	42.3×	0.086	RAD50
Regulation of endogenous retroelements	1	40.9×	0.086	SMARCE1
Transcriptional Regulation by MECP2	1	35.2×	0.086	PTEN
Impaired BRCA2 binding to RAD51	1	34.3×	0.086	RAD50
Resolution of D-loop Structures through Holliday Junction Intermediates	1	33.4×	0.086	RAD50
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	33.4×	0.086	SMARCE1
HDR through Single Strand Annealing (SSA)	1	32.5×	0.086	RAD50
Negative regulation of the PI3K/AKT network	1	30.9×	0.086	PTEN
Fcgamma receptor (FCGR) dependent phagocytosis	1	30.9×	0.086	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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell-cell adhesion involved in gastrulation	1	1532.0×	0.018	RIC8A
metanephric glomerular mesangial cell development	1	1532.0×	0.018	PDGFB
positive regulation of vascular associated smooth muscle cell dedifferentiation	1	1532.0×	0.018	PDGFB
positive regulation of metanephric mesenchymal cell migration	1	1532.0×	0.018	PDGFB
positive regulation of cellular response to drug	1	1532.0×	0.018	SUFU
regulation of mitotic recombination	1	766.0×	0.018	RAD50
multicellular organism development	1	766.0×	0.018	LEPR
negative regulation of phosphatidylinositol biosynthetic process	1	766.0×	0.018	PDGFB
smoothened signaling pathway involved in ventral spinal cord interneuron specification	1	766.0×	0.018	SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification	1	766.0×	0.018	SUFU
regulation of transport	1	766.0×	0.018	LEPR
cellular response to mycophenolic acid	1	766.0×	0.018	PDGFB
maintenance of protein localization in organelle	1	766.0×	0.018	SUFU
negative regulation of synaptic vesicle clustering	1	766.0×	0.018	PTEN
positive regulation of double-strand break repair	2	62.5×	0.018	SMARCE1, RAD50
negative regulation of osteoblast differentiation	2	53.8×	0.018	SUFU, PTEN
positive regulation of cell differentiation	2	48.6×	0.018	SMARCE1, NF2
positive regulation of glomerular filtration	1	510.7×	0.019	PDGFB
Schwann cell proliferation	1	510.7×	0.019	NF2
regulation of gliogenesis	1	510.7×	0.019	NF2
sexual reproduction	1	510.7×	0.019	LEPR
positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway	1	510.7×	0.019	PDGFB
negative regulation of keratinocyte migration	1	510.7×	0.019	PTEN
smooth muscle adaptation	1	383.0×	0.021	PDGFB
telomeric 3’ overhang formation	1	383.0×	0.021	RAD50
rhythmic synaptic transmission	1	383.0×	0.021	PTEN
positive regulation of hyaluronan biosynthetic process	1	383.0×	0.021	PDGFB
base-excision repair, AP site formation	1	306.4×	0.021	NTHL1
homologous chromosome segregation	1	306.4×	0.021	PTTG1
negative regulation of cell growth involved in contact inhibition	1	306.4×	0.021	NF2

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

18 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Mifepristone	Phase 3
Tranexamic Acid	Phase 3
ANTINEOPLASTON A10	Phase 2
Abemaciclib	Phase 2
Bevacizumab	Phase 2
Cabozantinib	Phase 2
Capivasertib	Phase 2
Edotreotide	Phase 2
Everolimus	Phase 2
Hydroxyurea	Phase 2
Ipilimumab	Phase 2
Nivolumab	Phase 2
Octreotide	Phase 2
Pasireotide	Phase 2
Pembrolizumab	Phase 2
Regorafenib	Phase 2
Trabectedin	Phase 2
Vismodegib	Phase 2

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 10

Druggability breadth: 8 of 11 evidence-associated genes (73%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAD50	1	2
LEPR	0	0
NTHL1	0	0
PTTG1	0	0
SMARCE1	0	0
MLLT10	0	0
SUFU	0	0
RIC8A	0	0
NF2	0	0
PDGFB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	RAD50

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
NTHL1	8	Binding:7, Functional:1
PTEN	8	Binding:8
SMARCE1	7	Binding:7
RAD50	7	Binding:7
LEPR	3	Binding:3
PDGFB	3	Binding:3
SUFU	1	Binding:1
RIC8A	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NTHL1	4.2.99.18	DNA-(apurinic or apyrimidinic site) lyase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	RAD50

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	1	RAD50
C	Druggable family + PDB, no drug	3	LEPR, NTHL1, PTEN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	7	PTTG1, SMARCE1, MLLT10, SUFU, RIC8A, NF2, PDGFB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LEPR	3	—
NTHL1	8	—
PTTG1	0	—
SMARCE1	7	—
MLLT10	0	—
SUFU	1	—
RIC8A	1	—
NF2	0	—
PDGFB	3	—
PTEN	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 127.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	66
PHASE2	31
PHASE1/PHASE2	10
EARLY_PHASE1	6
PHASE1	6
PHASE3	5
PHASE4	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04081701	PHASE4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT06377371	PHASE4	RECRUITING	Feasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE
NCT04386642	PHASE4	UNKNOWN	Tranexamic Acid Reduce Blood Loss in Meningioma Resection
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01655927	PHASE3	UNKNOWN	Efficacy of Tranexamic Acid in Brain Tumor Resections
NCT03015701	PHASE3	COMPLETED	S9005 Mifepristone in Meningioma
NCT03558516	PHASE3	COMPLETED	Magnesium and Intraoperative Blood Loss in Meningioma Surgery
NCT04305470	PHASE3	COMPLETED	Gleolan for Visualization of Newly Diagnosed or Recurrent Meningioma
NCT02523014	PHASE2	RECRUITING	Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
NCT02648997	PHASE2	ACTIVE_NOT_RECRUITING	An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma
NCT02847559	PHASE2	RECRUITING	Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma
NCT03604978	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Multi-fraction Stereotactic Radiosurgery With or Without Ipilimumab in Treating Patients With Recurrent Grade II-III Meningioma
NCT03971461	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
NCT04082520	PHASE2	RECRUITING	Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy
NCT04298541	PHASE2	NOT_YET_RECRUITING	Direct Comparison of Ga-68-DOTATATE and Ga-68-DOTATOC
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04659811	PHASE2	ACTIVE_NOT_RECRUITING	Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma
NCT04997317	PHASE1/PHASE2	RECRUITING	Treatment of Recurrent or Progressive Meningiomas With the Radiolabelled Somatostatin Antagonist 177Lu-satoreotide
NCT05278208	PHASE1/PHASE2	RECRUITING	Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
NCT05425004	PHASE2	RECRUITING	Cabozantinib for Patients With Recurrent or Progressive Meningioma
NCT05636618	PHASE1/PHASE2	RECRUITING	Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Tumors
NCT05940493	PHASE2	RECRUITING	Abemaciclib in Newly Diagnosed Meningioma Patients
NCT06126588	PHASE2	RECRUITING	Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
NCT06132685	PHASE2	RECRUITING	Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial
NCT06326190	PHASE2	RECRUITING	177Lu-DOTATATE for Recurrent Meningioma
NCT06607692	PHASE1/PHASE2	RECRUITING	Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined With the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).
NCT06640582	PHASE1/PHASE2	RECRUITING	TIL Therapy Combined With Pembrolizumab for Advanced Brain Cancer Including Gliomas and Meningiomas
NCT06684795	PHASE2	RECRUITING	FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery
NCT06710249	PHASE2	RECRUITING	Impact of Salovum® and SPC® Flakes on Brain Tumor Induced Edema
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07150806	PHASE1/PHASE2	RECRUITING	RYZ101 for the Treatment of Progressive or Recurrent Intracranial Meningioma
NCT07428616	PHASE2	RECRUITING	A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma
NCT07533942	PHASE2	NOT_YET_RECRUITING	A Study of JZP3507 (ONC206) in Recurrent Grade 2 or 3 Meningioma
NCT00003483	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Meningioma
NCT00589784	PHASE2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00706810	PHASE2	COMPLETED	Combination of Hydroxyurea and Verapamil for Refractory Meningiomas
NCT00859040	PHASE2	COMPLETED	Monthly SOM230C for Recurrent or Progressive Meningioma
NCT01117844	PHASE1/PHASE2	COMPLETED	Proton Radiation For Meningiomas and Hemangiopericytomas
NCT01967823	PHASE2	COMPLETED	T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
NCT02831257	PHASE2	COMPLETED	AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LUTETIUM OXODOTREOTIDE LU-177	4	4
EDOTREOTIDE GALLIUM GA-68	4	3
TRANEXAMIC ACID	4	3
AMINO ACIDS	4	2
ABEMACICLIB	4	1
ALPELISIB	4	1
AMINOLEVULINIC ACID HYDROCHLORIDE	4	1
BRIGATINIB	4	1
CAPIVASERTIB	4	1
HYDROXYUREA	4	1
MIFEPRISTONE	4	1
NERATINIB	4	1
RETIFANLIMAB	4	1
RIBOCICLIB	4	1
SELUMETINIB	4	1
SUNITINIB	4	1
VERAPAMIL	4	1
VISMODEGIB	4	1
DORDAVIPRONE	3	1
MAGNESIUM	3	1
ZANZALINTINIB	3	1
VISTUSERTIB	2	2
AR-42	2	1
DEXVERAPAMIL	2	1
LYSINE	2	1
ZIRCONIUM ZR 89 CREFMIRLIMAB BERDOXAM	2	1
CHEMBL3527065	0	2
CHEMBL275117	0	1
CHEMBL4517714	0	1
CHEMBL5405436	0	1