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Atlas / Disease / Brain glioma

Brain glioma

disease
On this page

Also known as brain malignant gliomamalignant glioma of brain

Summary

Brain glioma (MONDO:0005499) is a cancer (an umbrella term covering 8 Mondo subtypes) with 5 cohort genes (5 CIViC-evidence somatic drivers) and 20 clinical trials. Molecularly, IDH1 R132H confers sensitivity to Temozolomide in Brain Glioma (CIViC Level B); 8 further subtype–drug associations are mapped below. Top therapeutic interventions include fluorodopa f 18, panitumumab, and aglatimagene besadenovec.

At a glance

  • Classification: Cancer
  • Umbrella term: 8 Mondo subtypes
  • Cohort genes: 5
  • Clinical trials: 20
  • Precision-medicine evidence (CIViC): 9 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namebrain glioma
Mondo IDMONDO:0005499
DOIDDOID:0060108
NCITC162993
SNOMED CT254937005
UMLSC0349661
MedGen91163
GARD0024195
Anatomy (UBERON)UBERON:0000955
Is cancer (heuristic)yes

Also known as: brain malignant glioma · malignant glioma of brain

Disease family

An umbrella term covering 8 Mondo subtypes.

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

Related subtypes (8): supratentorial cancer, brain germinoma, brain sarcoma, cerebral ventricle cancer, infratentorial cancer, intracranial primitive neuroectodermal tumor, cancer of cerebellum, metastatic malignant neoplasm in the brain

Subtypes (8): brain glioblastoma, brain oligodendroglioma, brain stem glioma, diencephalic astrocytomas, childhood cerebral astrocytoma, ependymal tumor of brain, gliomatosis cerebri, chordoid glioma of the third ventricle

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 30 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
TERTActPRCCCIViC #79
EGFRActBRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SICCIViC #19
IDH1ActAML,CHOL,GB,GBM,HCC,HGGNOS,LGGNOS,MBL,MEL,MT,OS,PAST,PCM,PRAD,SKCMCIViC #26
IDH2ActAML,BLCA,CHOL,LGGNOS,OSCIViC #27
MMP2CIViC #3549

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
TERTOrphanet:146Differentiated thyroid carcinoma
TERTOrphanet:1501Adrenocortical carcinoma
TERTOrphanet:1775Dyskeratosis congenita
TERTOrphanet:2032Idiopathic pulmonary fibrosis
TERTOrphanet:2495Meningioma
TERTOrphanet:3322Hoyeraal-Hreidarsson syndrome
TERTOrphanet:457246Clear cell sarcoma of kidney
TERTOrphanet:618Familial melanoma
TERTOrphanet:88Idiopathic aplastic anemia
EGFROrphanet:251576Gliosarcoma
EGFROrphanet:251579Giant cell glioblastoma
IDH1Orphanet:163634Maffucci syndrome
IDH1Orphanet:251576Gliosarcoma
IDH1Orphanet:251579Giant cell glioblastoma
IDH1Orphanet:296Ollier disease
IDH1Orphanet:86845Acute myeloid leukaemia with myelodysplasia-related features
IDH1Orphanet:99646Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria
IDH2Orphanet:163634Maffucci syndrome
IDH2Orphanet:251589Anaplastic astrocytoma
IDH2Orphanet:251598Protoplasmic astrocytoma
IDH2Orphanet:251601Fibrillary astrocytoma
IDH2Orphanet:251604Gemistocytic astrocytoma
IDH2Orphanet:251627Oligodendroglioma
IDH2Orphanet:251630Anaplastic oligodendroglioma
IDH2Orphanet:251656Oligoastrocytoma
IDH2Orphanet:251663Anaplastic oligoastrocytoma
IDH2Orphanet:296Ollier disease
IDH2Orphanet:79315D-2-hydroxyglutaric aciduria
IDH2Orphanet:86845Acute myeloid leukaemia with myelodysplasia-related features
MMP2Orphanet:371428Multicentric osteolysis-nodulosis-arthropathy spectrum

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only5

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
TERTHGNC:11730ENSG00000164362O14746Telomerase reverse transcriptasecivic_evidence
EGFRHGNC:3236ENSG00000146648P00533Epidermal growth factor receptorcivic_evidence
IDH1HGNC:5382ENSG00000138413O75874Isocitrate dehydrogenase [NADP] cytoplasmiccivic_evidence
IDH2HGNC:5383ENSG00000182054P48735Isocitrate dehydrogenase [NADP], mitochondrialcivic_evidence
MMP2HGNC:7166ENSG00000087245P0825372 kDa type IV collagenasecivic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
TERTTelomerase reverse transcriptaseTelomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
EGFREpidermal growth factor receptorReceptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
IDH1Isocitrate dehydrogenase [NADP] cytoplasmicCatalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase.
IDH2Isocitrate dehydrogenase [NADP], mitochondrialPlays a role in intermediary metabolism and energy production.
MMP272 kDa type IV collagenaseUbiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.8

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
Protease17.3×0.224
Kinase15.5×0.224
Enzyme (other)24.8×0.224
Other/Unknown10.4×0.983

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
TERTOther/UnknownnoRT_dom, Telomerase_RT, Telomerase_RBD
EGFRKinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
IDH1Enzyme (other)yes1.1.1.42Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
IDH2Enzyme (other)yes1.1.1.42Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
MMP2Proteaseyes3.4.24.24FN_type2_dom, Hemopexin-like_dom, Pept_M10_metallopeptidase

Expression context

Cohort genes with no expression data: 0.

4 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)5
unknown0

Top tissues across cohort

TissueCohort genes
stromal cell of endometrium2
olfactory bulb1
type B pancreatic cell1
gingiva1
gingival epithelium1
nipple1
adrenal tissue1
corpus epididymis1
jejunal mucosa1
apex of heart1
gastrocnemius1
hindlimb stylopod muscle1
gall bladder1
mucosa of stomach1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
TERT105broadyesstromal cell of endometrium, type B pancreatic cell, olfactory bulb
EGFR285ubiquitousmarkernipple, gingiva, gingival epithelium
IDH1294ubiquitousmarkercorpus epididymis, jejunal mucosa, adrenal tissue
IDH2292ubiquitousmarkerapex of heart, gastrocnemius, hindlimb stylopod muscle
MMP2262ubiquitousmarkerstromal cell of endometrium, gall bladder, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

SymbolInteractor count
EGFR18,421
TERT5,717
IDH15,464
IDH24,912
MMP24,603

Intra-cohort edges

ABSources
EGFRIDH2biogrid_interaction
IDH1IDH2biogrid_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
EGFRP00533388
IDH1O7587461
TERTO1474623
MMP2P0825314
IDH2P4873511

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 76. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate12284.0×0.017IDH1
Extra-nuclear estrogen signaling268.2×0.017EGFR, MMP2
NADPH regeneration11142.0×0.022IDH1
NFE2L2 regulating TCA cycle genes1761.3×0.025IDH1
PLCG1 events in ERBB2 signaling1571.0×0.027EGFR
PTK6 promotes HIF1A stabilization1326.3×0.027EGFR
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence1326.3×0.027TERT
Inhibition of Signaling by Overexpressed EGFR1253.8×0.027EGFR
EGFR interacts with phospholipase C-gamma1228.4×0.027EGFR
EGFR Transactivation by Gastrin1228.4×0.027EGFR
ERBB2 Activates PTK6 Signaling1163.1×0.027EGFR
GRB2 events in EGFR signaling1152.3×0.027EGFR
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors1152.3×0.027EGFR
SHC1 events in EGFR signaling1142.8×0.027EGFR
Constitutive Signaling by EGFRvIII1142.8×0.027EGFR
ERBB2 Regulates Cell Motility1142.8×0.027EGFR
PI3K events in ERBB2 signaling1134.3×0.027EGFR
Signaling by ERBB2 ECD mutants1134.3×0.027EGFR
GAB1 signalosome1126.9×0.027EGFR
GRB2 events in ERBB2 signaling1126.9×0.027EGFR
Extension of Telomeres1120.2×0.027TERT
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants1114.2×0.027EGFR
Maturation of TCA enzymes and regulation of TCA cycle1114.2×0.027IDH2
Developmental Lineage of Mammary Gland Myoepithelial Cells1108.8×0.027EGFR
Signal transduction by L11103.8×0.027EGFR
Respiratory syncytial virus (RSV) attachment and entry199.3×0.027EGFR
SHC1 events in ERBB2 signaling195.2×0.027EGFR
NOTCH3 Activation and Transmission of Signal to the Nucleus195.2×0.027EGFR
Signaling by ERBB2 TMD/JMD mutants195.2×0.027EGFR
Telomere Extension By Telomerase191.4×0.027TERT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
glyoxylate cycle23370.4×1e-05IDH1, IDH2
isocitrate metabolic process21348.2×5e-05IDH1, IDH2
NADP+ metabolic process2612.8×2e-04IDH1, IDH2
2-oxoglutarate metabolic process2374.5×4e-04IDH1, IDH2
tricarboxylic acid cycle2204.3×0.001IDH1, IDH2
positive regulation of vascular associated smooth muscle cell proliferation2172.8×0.001TERT, MMP2
cellular response to estradiol stimulus2164.4×0.001EGFR, MMP2
positive regulation of G1/S transition of mitotic cell cycle2160.5×0.001TERT, EGFR
cellular response to amino acid stimulus2122.6×0.002EGFR, MMP2
positive regulation of miRNA transcription2116.2×0.002TERT, EGFR
RNA-templated transcription13370.4×0.003TERT
DNA strand elongation13370.4×0.003TERT
regulation of phospholipid catabolic process13370.4×0.003IDH1
siRNA transcription13370.4×0.003TERT
positive regulation of transdifferentiation13370.4×0.003TERT
negative regulation of cardiocyte differentiation13370.4×0.003EGFR
RNA-templated DNA biosynthetic process11685.2×0.004TERT
positive regulation of hair cycle11685.2×0.004TERT
regulation of phospholipid biosynthetic process11685.2×0.004IDH1
negative regulation of glial cell migration11685.2×0.004IDH2
negative regulation of matrix metallopeptidase secretion11685.2×0.004IDH2
positive regulation of protein kinase C signaling11123.5×0.006EGFR
morphogenesis of an epithelial fold1842.6×0.007EGFR
response to UV-A1842.6×0.007EGFR
positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway1842.6×0.007MMP2
NADPH regeneration1674.1×0.008IDH1
regulation of peptidyl-tyrosine phosphorylation1674.1×0.008EGFR
heart development231.5×0.008TERT, MMP2
intramembranous ossification1561.7×0.008MMP2
positive regulation of protein localization to nucleolus1561.7×0.008TERT

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 5 · Undrugged: 0

Druggability breadth: 5 of 5 evidence-associated genes (100%) 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
TERTBERBERINE
EGFRLEVODOPA
IDH1ENASIDENIB
IDH2ENASIDENIB
MMP2DOXYCYCLINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
EGFR1754
MMP2264
TERT104
IDH1104
IDH274

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
BERBERINE4TERT
DOXORUBICIN4MMP2, TERT
LEVODOPA4EGFR
CLOTRIMAZOLE4EGFR
ERLOTINIB HYDROCHLORIDE4EGFR
CISPLATIN4EGFR
PONATINIB4EGFR
AFATINIB4EGFR
CHROMIC CHLORIDE4EGFR
BACITRACIN4EGFR
ZINC CHLORIDE4EGFR
LAPATINIB DITOSYLATE4EGFR
VEMURAFENIB4EGFR
FEDRATINIB4EGFR
AXITINIB4EGFR
SORAFENIB4EGFR
DASATINIB ANHYDROUS4EGFR
NICLOSAMIDE4EGFR
SELUMETINIB4EGFR
TERFENADINE4EGFR
ALECTINIB4EGFR
NERATINIB4EGFR
IBRUTINIB4EGFR
AFATINIB DIMALEATE4EGFR
CABOZANTINIB4EGFR
DACOMITINIB4EGFR
DACOMITINIB ANHYDROUS4EGFR
CERITINIB4EGFR
VANDETANIB4EGFR
TRIBROMSALAN4EGFR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
EGFR6,531Binding:6211, Functional:173, ADMET:138, Toxicity:9
MMP2771Binding:735, ADMET:28, Functional:7, Unclassified:1
IDH1488Binding:475, Functional:12, ADMET:1
TERT391Binding:389, Functional:2
IDH284Binding:84

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
EGFR2.7.10.1receptor protein-tyrosine kinase
IDH11.1.1.42isocitrate dehydrogenase (NADP+)
IDH21.1.1.42isocitrate dehydrogenase (NADP+)
MMP23.4.24.24gelatinase A

Cohort genes with high screening signal

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

SymbolChEMBL assays
TERT391
EGFR6,531
IDH1488
MMP2771

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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.

CompoundMax phaseCohort target (bioactivity)
BERBERINE4TERT
DOXORUBICIN4MMP2, TERT
LEVODOPA4EGFR
CLOTRIMAZOLE4EGFR
ERLOTINIB HYDROCHLORIDE4EGFR
CISPLATIN4EGFR
PONATINIB4EGFR
AFATINIB4EGFR
CHROMIC CHLORIDE4EGFR
BACITRACIN4EGFR
ZINC CHLORIDE4EGFR
LAPATINIB DITOSYLATE4EGFR
VEMURAFENIB4EGFR
FEDRATINIB4EGFR
AXITINIB4EGFR
SORAFENIB4EGFR
DASATINIB ANHYDROUS4EGFR
NICLOSAMIDE4EGFR
SELUMETINIB4EGFR
TERFENADINE4EGFR
ALECTINIB4EGFR
NERATINIB4EGFR
IBRUTINIB4EGFR
AFATINIB DIMALEATE4EGFR
CABOZANTINIB4EGFR
DACOMITINIB4EGFR
DACOMITINIB ANHYDROUS4EGFR
CERITINIB4EGFR
VANDETANIB4EGFR
TRIBROMSALAN4EGFR

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)5TERT, EGFR, IDH1, IDH2, MMP2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE16
Not specified5
PHASE23
PHASE1/PHASE23
PHASE32
PHASE41

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04937244PHASE4UNKNOWNPilot Study Evaluating the Optimization of the ORBEYE Blue Light Filter During Fluorescence-Guided Resection of Gliomas
NCT03042416PHASE3COMPLETED18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety
NCT06417281PHASE3COMPLETEDPhotodynamic Diagnosis for Malignant Brain Glioma With 5-Aminolevulinic Acid（5-ALA）
NCT06018363PHASE1/PHASE2RECRUITINGClinical Study on the Treatment of Malignant Brain Glioma by QH104 Cell Injection
NCT00870181PHASE2COMPLETEDADV-TK Improves Outcome of Recurrent High-Grade Glioma
NCT01017653PHASE2TERMINATEDPanitumumab and Irinotecan for Malignant Gliomas
NCT02617134PHASE1/PHASE2UNKNOWNCAR-T Cell Immunotherapy in MUC1 Positive Solid Tumor
NCT02839954PHASE1/PHASE2UNKNOWNCAR-pNK Cell Immunotherapy in MUC1 Positive Relapsed or Refractory Solid Tumor
NCT04482933PHASE2WITHDRAWNHSV G207 With a Single Radiation Dose in Children With Recurrent High-Grade Glioma
NCT03011671PHASE1ACTIVE_NOT_RECRUITINGStudy of Acetazolamide With Temozolomide in Adults With Newly Diagnosed or Recurrent Malignant Glioma
NCT03152318PHASE1ACTIVE_NOT_RECRUITINGA Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2
NCT05686798PHASE1RECRUITINGAdenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.
NCT01550523PHASE1COMPLETEDPilot Immunotherapy Trial for Recurrent Malignant Gliomas
NCT03355794PHASE1COMPLETEDA Study of Ribociclib and Everolimus Following Radiation Therapy in Children With Newly Diagnosed Non-biopsied Diffuse Pontine Gliomas (DIPG) and RB+ Biopsied DIPG and High Grade Gliomas (HGG)
NCT03423992PHASE1UNKNOWNPersonalized Chimeric Antigen Receptor T Cell Immunotherapy for Patients With Recurrent Malignant Gliomas
NCT06747728Not specifiedRECRUITINGBevacizumab Neoadjuvant Therapy for New High-grade Gliomas in the Brain
NCT03176160Not specifiedWITHDRAWNLITT Palliative Treatment for Patients With Malignant Gliomas
NCT03984240Not specifiedCOMPLETEDThe Effects of Mild Sedation on Motor Function Networks in Patients With Brian Gliomas
NCT05593809Not specifiedUNKNOWNSingle Photon Emission Computed Tomography/Computed Tomography With Pentavalent 99mTc Dimercaptosuccinic Acid in Patients With Brain Glioma; Correlation With IDH Mutation
NCT05595863Not specifiedUNKNOWNCorrelation Between SPECT/CT and IDH Mutation in Brain Glioma

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
FLUORODOPA F 1841
PANITUMUMAB41
AGLATIMAGENE BESADENOVEC31

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 9 predictive associations from 10 curated evidence items; also 3 prognostic, 1 diagnostic, 1 predisposing.

Molecular subtypeTherapyEffectLevelCIViC
IDH1 R132HTemozolomideSensitivity/ResponseCIViC BEID2019 +1
IDH1 R132CTemozolomideSensitivity/ResponseCIViC BEID2327
IDH1 R132GTemozolomideSensitivity/ResponseCIViC BEID2334
IDH1 R132LTemozolomideSensitivity/ResponseCIViC BEID2018
IDH1 R132STemozolomideSensitivity/ResponseCIViC BEID2337
MMP2 SERUM LEVELSBevacizumabSensitivity/ResponseCIViC BEID1158
EGFR VIIINimotuzumabSensitivity/ResponseCIViC DEID1017
IDH1 MutationOlaparibSensitivity/ResponseCIViC DEID2933
IDH1 R132HBPTESSensitivity/ResponseCIViC DEID2324

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
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This page pulls from 74 datasets indexed by BioBTree:

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