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Atlas / Disease / Familial meningioma

Familial meningioma

disease
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Also known as hereditary meningiomahereditary meningioma (disease)meningiomameningioma, NF2-related, somaticmeningioma, SIS-related

Summary

Familial meningioma (MONDO:0011789) is a disease caused by SMARCE1 (GenCC Definitive), with 20 cohort genes and 127 clinical trials. Top therapeutic interventions include lutetium oxodotreotide lu-177, edotreotide gallium ga-68, and tranexamic acid.

At a glance

  • Causal gene: SMARCE1 (GenCC Definitive)
  • Cohort genes: 20
  • ClinVar variants: 1,159
  • Clinical trials: 127

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namefamilial meningioma
Mondo IDMONDO:0011789
MeSHC537443
OMIM607174
DOIDDOID:4586
NCITC5301
UMLSC3551915
MedGen764829
GARD0018385
Is cancer (heuristic)no

Also known as: familial meningioma · hereditary meningioma · hereditary meningioma (disease) · meningioma · meningioma, NF2-related, somatic · meningioma, SIS-related

Data availability: 1,159 ClinVar variants · 7 GenCC gene-disease records · 38 cell lines.

Disease family

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 › familial meningioma

Related subtypes (36): 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, grade III meningioma, papillary meningioma, optic tract meningioma, grade II meningioma, intracranial meningioma, supratentorial meningioma

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

600 retrieved; paginated sample, class counts are floors:

270 uncertain significance, 210 likely benign, 55 conflicting classifications of pathogenicity, 23 pathogenic, 14 likely pathogenic, 14 benign/likely benign, 10 benign, 4 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
142027NM_000314.8(PTEN):c.48T>A (p.Tyr16Ter)PTENPathogeniccriteria provided, multiple submitters, no conflicts
142259NM_000314.8(PTEN):c.741dup (p.Pro248fs)PTENPathogeniccriteria provided, multiple submitters, no conflicts
142269NM_000314.8(PTEN):c.737C>T (p.Pro246Leu)PTENPathogenicreviewed by expert panel
189474NM_000314.8(PTEN):c.202T>C (p.Tyr68His)PTENPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
189483NM_000314.8(PTEN):c.289C>T (p.Gln97Ter)PTENPathogeniccriteria provided, multiple submitters, no conflicts
189500NM_000314.8(PTEN):c.517C>T (p.Arg173Cys)PTENPathogenicreviewed by expert panel
216987NM_000314.8(PTEN):c.860C>G (p.Ser287Ter)PTENPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
231916NM_000314.8(PTEN):c.103A>G (p.Met35Val)PTENPathogenicreviewed by expert panel
280031NM_000314.8(PTEN):c.634+5G>APTENPathogenicreviewed by expert panel
1069790NM_003079.5(SMARCE1):c.472C>T (p.Arg158Ter)SMARCE1Pathogeniccriteria provided, multiple submitters, no conflicts
1076751NC_000017.10:g.(?38785037)(38804103_?)delSMARCE1Pathogeniccriteria provided, single submitter
1425601NM_003079.5(SMARCE1):c.493G>T (p.Glu165Ter)SMARCE1Pathogeniccriteria provided, multiple submitters, no conflicts
1428058NM_003079.5(SMARCE1):c.808del (p.Arg272fs)SMARCE1Pathogeniccriteria provided, single submitter
1435484NM_003079.5(SMARCE1):c.688C>T (p.Gln230Ter)SMARCE1Pathogeniccriteria provided, single submitter
1459773NM_003079.5(SMARCE1):c.92del (p.Tyr31fs)SMARCE1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1460319NM_003079.5(SMARCE1):c.328G>T (p.Glu110Ter)SMARCE1Pathogeniccriteria provided, multiple submitters, no conflicts
1740283NM_003079.5(SMARCE1):c.439del (p.Ser147fs)SMARCE1Pathogeniccriteria provided, single submitter
1748232NM_003079.5(SMARCE1):c.554del (p.Gly185fs)SMARCE1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1755184NM_003079.5(SMARCE1):c.673C>T (p.Gln225Ter)SMARCE1Pathogeniccriteria provided, multiple submitters, no conflicts
212264NM_003079.5(SMARCE1):c.624_627del (p.Ser208fs)SMARCE1Pathogeniccriteria provided, multiple submitters, no conflicts
239495NM_003079.5(SMARCE1):c.525del (p.Ala176fs)SMARCE1Pathogeniccriteria provided, single submitter
2664741NM_003079.5(SMARCE1):c.587del (p.Phe196fs)SMARCE1Pathogeniccriteria provided, multiple submitters, no conflicts
2709971NM_003079.5(SMARCE1):c.506del (p.Pro169fs)SMARCE1Pathogeniccriteria provided, single submitter
2792205NM_003079.5(SMARCE1):c.694C>T (p.Gln232Ter)SMARCE1Pathogeniccriteria provided, single submitter
2855068NM_003079.5(SMARCE1):c.376T>G (p.Tyr126Asp)SMARCE1Pathogeniccriteria provided, single submitter
2972862NM_003079.5(SMARCE1):c.814del (p.Arg272fs)SMARCE1Pathogeniccriteria provided, single submitter
3223094NM_003079.5(SMARCE1):c.275dup (p.Leu93fs)SMARCE1Pathogeniccriteria provided, multiple submitters, no conflicts
3064176NM_014575.4(SCHIP1):c.1354C>T (p.Arg452Ter)IQCJ-SCHIP1Likely pathogeniccriteria provided, single submitter
2677254NM_000268.4(NF2):c.599+1G>CNF2Likely pathogeniccriteria provided, single submitter
1785916NM_000314.8(PTEN):c.210-12C>GPTENLikely pathogeniccriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 26 · Orphanet: 55 · 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.

GeneClassificationInheritanceDiseaseRecords
SMARCE1DefinitiveAutosomal dominantfamilial meningioma9
MN1LimitedAutosomal dominantfamilial meningioma5
NF2LimitedUnknownfamilial meningioma5
PDGFBLimitedAutosomal dominantfamilial meningioma7

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SMARCE1Orphanet:1465Coffin-Siris syndrome
SMARCE1Orphanet:2495Meningioma
SMARCE1Orphanet:263662Familial multiple meningioma
MN1Orphanet:263662Familial multiple meningioma
MN1Orphanet:693549Facial dysmorphism-Intellectual disability-rhombencephalosynapsis syndrome
NF2Orphanet:2495Meningioma
NF2Orphanet:634475Mosaic NF2-related schwannomatosis
NF2Orphanet:637Full NF2-related schwannomatosis
NF2Orphanet:93921Full schwannomatosis
PDGFBOrphanet:1980Bilateral striopallidodentate calcinosis
PDGFBOrphanet:2495Meningioma
PDGFBOrphanet:263662Familial multiple meningioma
PDGFBOrphanet:31112Dermatofibrosarcoma protuberans
LEPROrphanet:179494Obesity due to leptin receptor gene deficiency
BMPR1AOrphanet:157794Hereditary mixed polyposis syndrome
BMPR1AOrphanet:329971Generalized juvenile polyposis/juvenile polyposis coli
BMPR1AOrphanet:440437Familial colorectal cancer Type X
BMPR1AOrphanet:79076Juvenile polyposis of infancy
TNRC6AOrphanet:86814Familial adult myoclonic epilepsy
SUFUOrphanet:2495Meningioma
SUFUOrphanet:251858Medulloblastoma with extensive nodularity
SUFUOrphanet:251863Desmoplastic/nodular medulloblastoma
SUFUOrphanet:263662Familial multiple meningioma
SUFUOrphanet:280200Microform holoprosencephaly
SUFUOrphanet:377Gorlin syndrome
SUFUOrphanet:475Isolated Joubert syndrome
CDKN2AOrphanet:1333Familial pancreatic carcinoma
CDKN2AOrphanet:1501Adrenocortical carcinoma
CDKN2AOrphanet:252206Melanoma and neural system tumor syndrome
CDKN2AOrphanet:404560Familial atypical multiple mole melanoma syndrome
CDKN2AOrphanet:524Li-Fraumeni syndrome
CDKN2AOrphanet:585909B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2AOrphanet:618Familial melanoma
CDKN2AOrphanet:99861Precursor T-cell acute lymphoblastic leukemia
EXTL3Orphanet:508533Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome
KLLNOrphanet:201Cowden syndrome
KLLNOrphanet:227535Hereditary breast cancer
PTENOrphanet:109Bannayan-Riley-Ruvalcaba syndrome
PTENOrphanet:137608Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTENOrphanet:145Hereditary breast and/or ovarian cancer syndrome
PTENOrphanet:201Cowden syndrome
PTENOrphanet:210548Macrocephaly-intellectual disability-autism syndrome
PTENOrphanet:2969Proteus-like syndrome
PTENOrphanet:494547Squamous cell carcinoma of the hypopharynx
PTENOrphanet:494550Squamous cell carcinoma of the larynx
PTENOrphanet:500464Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTENOrphanet:500478Squamous cell carcinoma of the oropharynx
PTENOrphanet:502363Squamous cell carcinoma of the oral cavity
PTENOrphanet:502366Squamous cell carcinoma of the lip
PTENOrphanet:65285Lhermitte-Duclos disease

Cohort genes → proteins

20 cohort genes, 20 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only2
multi_evidence18

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SMARCE1HGNC:11109ENSG00000073584Q969G3SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1gencc,clinvar
MN1HGNC:7180ENSG00000169184Q10571Transcriptional activator MN1gencc,clinvar
NF2HGNC:7773ENSG00000186575P35240Merlingencc,clinvar
PDGFBHGNC:8800ENSG00000100311P01127Platelet-derived growth factor subunit Bgencc,clinvar
LEPRHGNC:6554ENSG00000116678P48357Leptin receptorcivic_evidence
PTTG1HGNC:9690ENSG00000164611O95997Securincivic_evidence
BMPR1AHGNC:1076ENSG00000107779P36894Bone morphogenetic protein receptor type-1Aclinvar
TNRC6AHGNC:11969ENSG00000090905Q8NDV7Trinucleotide repeat-containing gene 6A proteinclinvar
SUFUHGNC:16466ENSG00000107882Q9UMX1Suppressor of fused homologclinvar
CDKN2AHGNC:1787ENSG00000147889P42771Cyclin-dependent kinase inhibitor 2Aclinvar
CSMD3HGNC:19291ENSG00000164796Q7Z407CUB and sushi domain-containing protein 3clinvar
RAB44HGNC:21068ENSG00000255587Q7Z6P3Ras-related protein Rab-44clinvar
FAT3HGNC:23112ENSG00000165323Q8TDW7Protocadherin Fat 3clinvar
FNDC3BHGNC:24670ENSG00000075420Q53EP0Fibronectin type III domain-containing protein 3Bclinvar
EXTL3HGNC:3518ENSG00000012232O43909Exostosin-like 3clinvar
KLLNHGNC:37212ENSG00000227268B2CW77Killinclinvar
IQCJ-SCHIP1HGNC:38842ENSG00000283154B3KU38IQCJ-SCHIP1 readthrough transcript proteinclinvar
PTENHGNC:9588ENSG00000171862P60484Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENclinvar
RARAHGNC:9864ENSG00000131759P10276Retinoic acid receptor alphaclinvar
RECQL4HGNC:9949ENSG00000160957O94761ATP-dependent DNA helicase Q4clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SMARCE1SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
MN1Transcriptional activator MN1Transcriptional activator which specifically regulates expression of TBX22 in the posterior region of the developing palate.
NF2MerlinProbable 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.
PDGFBPlatelet-derived growth factor subunit BGrowth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.
LEPRLeptin receptorReceptor for hormone LEP/leptin.
PTTG1SecurinRegulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair.
BMPR1ABone morphogenetic protein receptor type-1AOn ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
TNRC6ATrinucleotide repeat-containing gene 6A proteinPlays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs).
SUFUSuppressor of fused homologNegative regulator in the hedgehog/smoothened signaling pathway.
CDKN2ACyclin-dependent kinase inhibitor 2AActs as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CSMD3CUB and sushi domain-containing protein 3Involved in dendrite development.
RAB44Ras-related protein Rab-44The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.
FAT3Protocadherin Fat 3May play a role in the interactions between neurites derived from specific subsets of neurons during development.
FNDC3BFibronectin type III domain-containing protein 3BMay be a positive regulator of adipogenesis.
EXTL3Exostosin-like 3Glycosyltransferase which regulates the biosynthesis of heparan sulfate (HS).
KLLNKillinDNA-binding protein involved in S phase checkpoint control-coupled apoptosis by mediating p53/TP53-induced apoptosis.
IQCJ-SCHIP1IQCJ-SCHIP1 readthrough transcript proteinMay play a role in action potential conduction in myelinated cells through the organization of molecular complexes at nodes of Ranvier and axon initial segments.
PTENPhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENDual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
RARARetinoic acid receptor alphaReceptor for retinoic acid.
RECQL4ATP-dependent DNA helicase Q4An ATP-dependent DNA helicase which unwinds dsDNA with a 3’-overhang in a 3’-5’ direction.

Protein-family classification

Druggable: 8 · Difficult: 1 · Unknown: 11 · Druggable fraction: 0.4

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.

FamilyGenesFoldFDR
Nuclear receptor119.3×0.288
Complement113.4×0.288
Antibody/Immunoglobulin22.9×0.396
Phosphatase14.2×0.427
Kinase11.4×0.694
Enzyme (other)21.2×0.694
Other/Unknown111.0×0.696
Scaffold/PPI10.9×0.696

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SMARCE1Other/UnknownnoHMG_box_dom, HMG_box_dom_sf
MN1Other/UnknownnoMN1
NF2Other/UnknownnoFERM_domain, Ez/rad/moesin-like, Moesin_tail_sf
PDGFBOther/UnknownnoPDGF/VEGF_dom, PDGF_N, PD_growth_factor_CS
LEPRAntibody/ImmunoglobulinyesHematopoietin_rcpt_Gp130_CS, Hempt_rcpt_S_F1_CS, FN3_dom
PTTG1Other/UnknownnoSecurin_separation_inhibitor
BMPR1AKinaseyes2.7.10.2TGFB_receptor, Activin_recp, Prot_kinase_dom
TNRC6AOther/UnknownnoNucleotide-bd_a/b_plait_sf, Argonaute_hook_dom, TNRC6_PABC-bd
SUFUOther/UnknownnoSuppressor_of_fused, Suppressor_of_fused_euk, SUFU-like_domain
CDKN2AScaffold/PPInoAnkyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CSMD3ComplementyesSushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
RAB44Other/UnknownnoSmall_GTPase, EF_hand_dom, Small_GTP-bd
FAT3Other/UnknownnoEGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
FNDC3BAntibody/ImmunoglobulinyesFN3_dom, Ig-like_fold, FN3_sf
EXTL3Enzyme (other)yes2.4.1.223Exostosin, GT64_dom, Nucleotide-diphossugar_trans
KLLNOther/Unknownno
IQCJ-SCHIP1Other/UnknownnoSCHIP_1_C, IQCJ-SCHIP1_N, SCHIP_1
PTENPhosphataseyes3.1.3.16Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
RARANuclear receptoryesNucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RECQL4Enzyme (other)yes3.6.4.12Helicase_C-like, DNA_helicase_ATP-dep_RecQ, DEAD/DEAH_box_helicase_dom

Expression context

Cohort genes with no expression data: 0.

18 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)20
unknown0

Top tissues across cohort

TissueCohort genes
calcaneal tendon5
ventricular zone4
ganglionic eminence2
stromal cell of endometrium2
secondary oocyte2
Brodmann (1909) area 232
male germ line stem cell (sensu Vertebrata) in testis2
middle temporal gyrus2
monocyte2
embryo1
skeletal muscle tissue of biceps brachii1
vastus lateralis1
dorsal motor nucleus of vagus nerve1
endometrium epithelium1
apex of heart1
olfactory bulb1
type B pancreatic cell1
choroid plexus epithelium1
trabecular bone tissue1
trigeminal ganglion1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SMARCE1197ubiquitousmarkercalcaneal tendon, embryo, ganglionic eminence
MN1252ubiquitousmarkerganglionic eminence, vastus lateralis, skeletal muscle tissue of biceps brachii
NF2283ubiquitousmarkerendometrium epithelium, stromal cell of endometrium, dorsal motor nucleus of vagus nerve
PDGFB259ubiquitousmarkerolfactory bulb, type B pancreatic cell, apex of heart
LEPR272broadmarkertrabecular bone tissue, choroid plexus epithelium, trigeminal ganglion
PTTG1246ubiquitousmarkeroocyte, secondary oocyte, ventricular zone
BMPR1A284ubiquitousmarkersecondary oocyte, calcaneal tendon, saphenous vein
TNRC6A143ubiquitousmarkercorpus callosum, calcaneal tendon, sural nerve
SUFU226ubiquitousyesupper arm skin, kidney epithelium, vena cava
CDKN2A220ubiquitousmarkerparotid gland, cervix squamous epithelium, pituitary gland
CSMD3129broadmarkermiddle temporal gyrus, Brodmann (1909) area 23, male germ line stem cell (sensu Vertebrata) in testis
RAB4475tissue_specificmarkerbone marrow, monocyte, leukocyte
FAT3194broadmarkerbuccal mucosa cell, Brodmann (1909) area 23, middle temporal gyrus
FNDC3B275ubiquitousmarkercartilage tissue, calcaneal tendon, tibia
EXTL3210ubiquitousmarkerstromal cell of endometrium, ventricular zone, cortical plate
KLLN149markertibialis anterior, male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell
IQCJ-SCHIP1133broadmarkerventricular zone, C1 segment of cervical spinal cord, superior frontal gyrus
PTEN256ubiquitousmarkersperm, endothelial cell, calcaneal tendon
RARA276ubiquitousmarkermammary duct, monocyte, granulocyte
RECQL4212ubiquitousyeslower esophagus mucosa, ventricular zone, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PTEN11,626
CDKN2A9,311
RECQL46,330
RARA3,885
BMPR1A3,316
NF23,208
SMARCE12,977
PDGFB2,424
LEPR2,243
PTTG12,225

Intra-cohort edges

ABSources
CSMD3FAT3string_interaction
FAT3PDGFBbiogrid_interaction, intact
IQCJ-SCHIP1NF2string_interaction
KLLNPTENstring_interaction

Structural data

PDB: 13 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
RARAP1027614
PTENP6048412
BMPR1AP3689411
SUFUQ9UMX110
LEPRP483579
SMARCE1Q969G38
NF2P352406
PDGFBP011276
CDKN2AP427715
EXTL3O439094
PTTG1O959972
TNRC6AQ8NDV72
RECQL4O947612

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
FNDC3BQ53EP075.78
IQCJ-SCHIP1B3KU3858.27
RAB44Q7Z6P358.25
KLLNB2CW7751.20
MN1Q1057142.47
CSMD3Q7Z407
FAT3Q8TDW7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 140. Enrichment computed across 20 evidence-associated genes (13 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 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Regulation of PTEN mRNA translation2175.7×0.007TNRC6A, PTEN
Evasion of Oncogene Induced Senescence Due to p14ARF Defects1878.5×0.023CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects1878.5×0.023CDKN2A
TGFBR3 expression270.3×0.023TNRC6A, RARA
Oncogene Induced Senescence251.7×0.023TNRC6A, CDKN2A
Transcriptional Regulation by MECP2248.8×0.023TNRC6A, PTEN
Transcriptional Regulation by VENTX240.9×0.023TNRC6A, CDKN2A
PTEN Loss of Function in Cancer1439.2×0.027PTEN
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK41439.2×0.027CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK41439.2×0.027CDKN2A
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function1439.2×0.027CDKN2A
Diseases of Cellular Senescence1292.8×0.027CDKN2A
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects1292.8×0.027CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK61292.8×0.027CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects1292.8×0.027CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK61292.8×0.027CDKN2A
Diseases of cellular response to stress1292.8×0.027CDKN2A
MITF-M-dependent gene expression227.9×0.027SMARCE1, CDKN2A
TP53 Regulates Metabolic Genes220.0×0.032TNRC6A, PTEN
MITF-M-regulated melanocyte development217.6×0.039SMARCE1, CDKN2A
Post-transcriptional silencing by small RNAs1125.5×0.053TNRC6A
Competing endogenous RNAs (ceRNAs) regulate PTEN translation1109.8×0.055TNRC6A
Regulation of CDH11 mRNA translation by microRNAs197.6×0.055TNRC6A
Regulation of NPAS4 mRNA translation197.6×0.055TNRC6A
Regulation of PD-L1(CD274) translation197.6×0.055TNRC6A
Oxidative Stress Induced Senescence213.9×0.055TNRC6A, CDKN2A
RUNX3 regulates p14-ARF187.8×0.058CDKN2A
Signaling by Leptin179.9×0.058LEPR
Regulation of PTEN localization179.9×0.058PTEN
Regulation of CDH1 mRNA translation by microRNAs179.9×0.058TNRC6A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
neural plate mediolateral regionalization1887.0×0.020BMPR1A
paraxial mesoderm structural organization1887.0×0.020BMPR1A
negative regulation of cytoskeleton organization1887.0×0.020IQCJ-SCHIP1
Sertoli cell fate commitment1887.0×0.020RARA
metanephric glomerular mesangial cell development1887.0×0.020PDGFB
histamine secretion mediated by IgE immunoglobulin1887.0×0.020RAB44
positive regulation of cardiac ventricle development1887.0×0.020BMPR1A
positive regulation of vascular associated smooth muscle cell dedifferentiation1887.0×0.020PDGFB
fibrous ring of heart morphogenesis1887.0×0.020BMPR1A
positive regulation of metanephric mesenchymal cell migration1887.0×0.020PDGFB
positive regulation of cellular response to drug1887.0×0.020SUFU
negative regulation of osteoblast proliferation2161.3×0.020MN1, NF2
ectoderm development2126.7×0.020NF2, BMPR1A
negative regulation of cell-matrix adhesion293.4×0.020NF2, CDKN2A
negative regulation of ubiquitin-dependent protein catabolic process288.7×0.020SUFU, CDKN2A
outflow tract septum morphogenesis268.2×0.020BMPR1A, RARA
negative regulation of miRNA transcription265.7×0.020PDGFB, RARA
mesoderm formation252.2×0.020NF2, BMPR1A
positive regulation of vascular associated smooth muscle cell proliferation245.5×0.020PDGFB, BMPR1A
regulation of protein stability319.9×0.020NF2, CDKN2A, PTEN
negative regulation of cell population proliferation48.9×0.020NF2, CDKN2A, PTEN, RARA
multicellular organism development1443.5×0.022LEPR
negative regulation of phosphatidylinositol biosynthetic process1443.5×0.022PDGFB
smoothened signaling pathway involved in ventral spinal cord interneuron specification1443.5×0.022SUFU
smoothened signaling pathway involved in spinal cord motor neuron cell fate specification1443.5×0.022SUFU
nuclear body organization1443.5×0.022CDKN2A
regulation of transport1443.5×0.022LEPR
positive regulation of binding1443.5×0.022RARA
cellular response to mycophenolic acid1443.5×0.022PDGFB
maintenance of protein localization in organelle1443.5×0.022SUFU

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 18

Druggability breadth: 8 of 20 evidence-associated genes (40%) 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.

SymbolExample approved molecule
BMPR1AMOMELOTINIB
RARABEXAROTENE

Top cohort targets by molecule count

SymbolMoleculesMax phase
BMPR1A114
RARA114
SMARCE100
MN100
NF200
PDGFB00
LEPR00
PTTG100
TNRC6A00
SUFU00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
MOMELOTINIB4BMPR1A
GILTERITINIB4BMPR1A
DASATINIB4BMPR1A
BEXAROTENE4RARA
ADAPALENE4RARA
TAZAROTENE4RARA
TAMIBAROTENE4RARA
TRIFAROTENE4RARA
TRETINOIN4RARA
ALITRETINOIN4RARA
SARACATINIB3BMPR1A
LESTAURTINIB3BMPR1A
AT-92832BMPR1A
ZILURGISERTIB2BMPR1A
KER-0472BMPR1A
NRX1951832RARA
CONESSINE2RARA
GLIQUIDONE2RARA
MOLIBRESIB2RARA
KW-24491BMPR1A
XL-2281BMPR1A
Y-399831BMPR1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
RARA368Binding:279, Functional:85, ADMET:4
BMPR1A169Binding:166, ADMET:3
PTEN8Binding:8
SMARCE17Binding:7
PDGFB3Binding:3
LEPR3Binding:3
CDKN2A2Binding:2
SUFU1Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BMPR1A2.7.10.2non-specific protein-tyrosine kinase
EXTL32.4.1.223glucuronosyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase
PTEN3.1.3.16, 3.1.3.67protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
RECQL43.6.4.12DNA helicase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
BMPR1A169
RARA368

Pharmacogenomics

Cohort genes with a PharmGKB record: 19; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

22 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.

CompoundMax phaseCohort target (bioactivity)
MOMELOTINIB4BMPR1A
GILTERITINIB4BMPR1A
DASATINIB4BMPR1A
BEXAROTENE4RARA
ADAPALENE4RARA
TAZAROTENE4RARA
TAMIBAROTENE4RARA
TRIFAROTENE4RARA
TRETINOIN4RARA
ALITRETINOIN4RARA
SARACATINIB3BMPR1A
LESTAURTINIB3BMPR1A
AT-92832BMPR1A
ZILURGISERTIB2BMPR1A
KER-0472BMPR1A
NRX1951832RARA
CONESSINE2RARA
GLIQUIDONE2RARA
MOLIBRESIB2RARA
KW-24491BMPR1A
XL-2281BMPR1A
Y-399831BMPR1A

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2BMPR1A, RARA
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug4LEPR, EXTL3, PTEN, RECQL4
DDruggable family + AlphaFold only, no drug2CSMD3, FNDC3B
EDifficult family or no structure, no drug12SMARCE1, MN1, NF2, PDGFB, PTTG1, TNRC6A, SUFU, CDKN2A, RAB44, FAT3 (+2 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SMARCE17—
MN10—
NF20—
PDGFB3—
LEPR3—
PTTG10—
TNRC6A0—
SUFU1—
CDKN2A2—
CSMD30—
RAB440—
FAT30—
FNDC3B0—
EXTL30—
KLLN0—
IQCJ-SCHIP10—
PTEN8—
RECQL40—

Clinical trials & evidence

Clinical trials

Clinical trials: 127.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified66
PHASE231
PHASE1/PHASE210
EARLY_PHASE16
PHASE16
PHASE35
PHASE43

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04081701PHASE4RECRUITING68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT06377371PHASE4RECRUITINGFeasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE
NCT04386642PHASE4UNKNOWNTranexamic Acid Reduce Blood Loss in Meningioma Resection
NCT00517959PHASE3UNKNOWNSCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01655927PHASE3UNKNOWNEfficacy of Tranexamic Acid in Brain Tumor Resections
NCT03015701PHASE3COMPLETEDS9005 Mifepristone in Meningioma
NCT03558516PHASE3COMPLETEDMagnesium and Intraoperative Blood Loss in Meningioma Surgery
NCT04305470PHASE3COMPLETEDGleolan for Visualization of Newly Diagnosed or Recurrent Meningioma
NCT02523014PHASE2RECRUITINGVismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
NCT02648997PHASE2ACTIVE_NOT_RECRUITINGAn Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma
NCT02847559PHASE2RECRUITINGOptune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma
NCT03604978PHASE1/PHASE2ACTIVE_NOT_RECRUITINGNivolumab and Multi-fraction Stereotactic Radiosurgery With or Without Ipilimumab in Treating Patients With Recurrent Grade II-III Meningioma
NCT03971461PHASE2ACTIVE_NOT_RECRUITINGPhase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
NCT04082520PHASE2RECRUITINGLutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy
NCT04298541PHASE2NOT_YET_RECRUITINGDirect Comparison of Ga-68-DOTATATE and Ga-68-DOTATOC
NCT04374305PHASE2RECRUITINGInnovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04659811PHASE2ACTIVE_NOT_RECRUITINGStereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma
NCT04997317PHASE1/PHASE2RECRUITINGTreatment of Recurrent or Progressive Meningiomas With the Radiolabelled Somatostatin Antagonist 177Lu-satoreotide
NCT05278208PHASE1/PHASE2RECRUITINGLutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
NCT05425004PHASE2RECRUITINGCabozantinib for Patients With Recurrent or Progressive Meningioma
NCT05636618PHASE1/PHASE2RECRUITINGTargeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Tumors
NCT05940493PHASE2RECRUITINGAbemaciclib in Newly Diagnosed Meningioma Patients
NCT06126588PHASE2RECRUITINGCombination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
NCT06132685PHASE2RECRUITINGPost-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial
NCT06326190PHASE2RECRUITING177Lu-DOTATATE for Recurrent Meningioma
NCT06607692PHASE1/PHASE2RECRUITINGStudy 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).
NCT06640582PHASE1/PHASE2RECRUITINGTIL Therapy Combined With Pembrolizumab for Advanced Brain Cancer Including Gliomas and Meningiomas
NCT06684795PHASE2RECRUITINGFG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery
NCT06710249PHASE2RECRUITINGImpact of Salovum® and SPC® Flakes on Brain Tumor Induced Edema
NCT06804655PHASE2NOT_YET_RECRUITINGPharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07150806PHASE1/PHASE2RECRUITINGRYZ101 for the Treatment of Progressive or Recurrent Intracranial Meningioma
NCT07428616PHASE2RECRUITINGA Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma
NCT07533942PHASE2NOT_YET_RECRUITINGA Study of JZP3507 (ONC206) in Recurrent Grade 2 or 3 Meningioma
NCT00003483PHASE2TERMINATEDAntineoplaston Therapy in Treating Patients With Meningioma
NCT00589784PHASE2COMPLETEDPhase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00706810PHASE2COMPLETEDCombination of Hydroxyurea and Verapamil for Refractory Meningiomas
NCT00859040PHASE2COMPLETEDMonthly SOM230C for Recurrent or Progressive Meningioma
NCT01117844PHASE1/PHASE2COMPLETEDProton Radiation For Meningiomas and Hemangiopericytomas
NCT01967823PHASE2COMPLETEDT Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
NCT02831257PHASE2COMPLETEDAZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
LUTETIUM OXODOTREOTIDE LU-17744
EDOTREOTIDE GALLIUM GA-6843
TRANEXAMIC ACID43
AMINO ACIDS42
ABEMACICLIB41
ALPELISIB41
AMINOLEVULINIC ACID HYDROCHLORIDE41
BRIGATINIB41
CAPIVASERTIB41
HYDROXYUREA41
MIFEPRISTONE41
NERATINIB41
RETIFANLIMAB41
RIBOCICLIB41
SELUMETINIB41
SUNITINIB41
VERAPAMIL41
VISMODEGIB41
DORDAVIPRONE31
MAGNESIUM31
ZANZALINTINIB31
VISTUSERTIB22
AR-4221
DEXVERAPAMIL21
LYSINE21
ZIRCONIUM ZR 89 CREFMIRLIMAB BERDOXAM21
CHEMBL352706502
CHEMBL27511701
CHEMBL451771401
CHEMBL540543601

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 70

This page pulls from 70 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot