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Atlas / Disease / Malignant glioma

Malignant glioma

disease
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Also known as glial cell tumourgliomaglioma, malignanthigh grade gliomahigh-grade gliomamalignant glial neoplasmmalignant glial tumormalignant glial tumourmalignant neuroglial neoplasmmalignant neuroglial tumormalignant neuroglial tumourneuroglial tumorneuroglial tumour

Summary

Malignant glioma (MONDO:0100342) is a cancer (an umbrella term covering 12 Mondo subtypes) with 11 cohort genes (3 GWAS associations across 1 studies; 11 CIViC-evidence somatic drivers; 5 ClinVar predisposition records) and 963 clinical trials. Molecularly, IDH2 Mutation OR IDH1 Mutation confers sensitivity to Vorasidenib in Glioma (CIViC Level A); 24 further subtype–drug associations are mapped below. Top therapeutic interventions include larotrectinib, dabrafenib, and lapatinib.

At a glance

  • Classification: Cancer
  • Umbrella term: 12 Mondo subtypes
  • Cohort genes: 11
  • GWAS associations: 3
  • ClinVar variants: 5
  • Clinical trials: 963
  • Precision-medicine evidence (CIViC): 25 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namemalignant glioma
Mondo IDMONDO:0100342
DOIDDOID:3070
NCITC4822
UMLSC0555198
MedGen107826
GARD0026148
MedDRA10018338
Is cancer (heuristic)yes

Also known as: glial cell tumour · glioma · glioma, malignant · high grade glioma · high-grade glioma · malignant glial neoplasm · malignant glial tumor · malignant glial tumour · malignant glioma · malignant neuroglial neoplasm · malignant neuroglial tumor · malignant neuroglial tumour · neuroglial tumor · neuroglial tumour

Data availability: 5 ClinVar variants · 3 GWAS associations (1 study) · 7 cell lines.

Disease family

An umbrella term covering 12 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 › malignant glioma

Related subtypes (19): central nervous system primitive neuroectodermal neoplasm, brain cancer, central nervous system sarcoma, primary central nervous system lymphoma, central nervous system germinoma, central nervous system melanocytic neoplasm, central nervous system endodermal sinus tumor, spinal cord cancer, malignant carotid body paraganglioma, malignant adrenal gland pheochromocytoma, malignant jugulotympanic paraganglioma, pheochromocytoma/paraganglioma syndrome 2, pheochromocytoma/paraganglioma syndrome 5, central nervous system Ewing sarcoma/peripheral primitive neuroectodermal tumor, choriocarcinoma of the central nervous system, mixed germ cell tumor of central nervous system, embryonal carcinoma of the central nervous system, malignant tumor of meninges, malignant central nervous system mesenchymal, non-meningothelial neoplasm

Subtypes (12): spinal cord glioma, granular cell cancer, neurofibroma of gallbladder, neurofibroma of the heart, brain glioma, high grade astrocytic tumor, malignant perineurioma, malignant peripheral nerve sheath tumor, oligodendroglial tumor, grade III glioma, isolated melanotic schwannoma, pediatric high-grade glioma

Genetics & variants

GWAS landscape

3 GWAS associations across 1 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs37516677e-07LMF1?2.17
rs28160623e-06DYNLL1P3 - PAX7?2.03
rs78277911e-05NDUFB9?1.91

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90134571Lin JC20221950Genome-Wide Association Study Identifies Multiple Susceptibility Loci for Malignant Neoplasms of the Brain in Taiwan.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic3

MAF distribution

BucketVariants
common (>=0.05)3
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
synonymous_variant1
intergenic_variant1
intron_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs375166716954554C>T0.05synonymous_variantLMF17e-07Tier 4: intronic/intergenic
rs2816062118577408G>A,C0.05intergenic_variantDYNLL1P3 - PAX73e-06Tier 4: intronic/intergenic
rs78277918124549270A>G0.05intron_variantNDUFB91e-05Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

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

ClinVarVariant (HGVS)GeneClassificationReview
127463NM_000051.4(ATM):c.8786+1G>AATMPathogenicreviewed by expert panel
91268NM_000251.3(MSH2):c.97A>G (p.Thr33Ala)MSH2Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
1751748NM_000038.6(APC):c.6125G>A (p.Cys2042Tyr)APCUncertain significancecriteria provided, multiple submitters, no conflicts
127824NM_000546.6(TP53):c.847C>T (p.Arg283Cys)TP53Likely benignreviewed by expert panel
406605NM_000546.6(TP53):c.760A>G (p.Ile254Val)TP53Likely benignreviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 75 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
BRAFActBLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTCCIViC #5
EGFRActBRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SICCIViC #19
H3-3AActHGGNOS,PASTCIViC #2537
IDH1ActAML,CHOL,GB,GBM,HCC,HGGNOS,LGGNOS,MBL,MEL,MT,OS,PAST,PCM,PRAD,SKCMCIViC #26
IDH2ActAML,BLCA,CHOL,LGGNOS,OSCIViC #27
MGMTCIViC #34
PDGFRAActCSCC,GB,GBM,HGGNOS,LGGNOS,LUSC,PASTCIViC #38
TP53LoFACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WTCIViC #45
APCLoFAML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVACIViC #66
MSH2CIViC #3628
ATMLoFBLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTCCIViC #69

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BRAFOrphanet:1340Cardiofaciocutaneous syndrome
BRAFOrphanet:146Differentiated thyroid carcinoma
BRAFOrphanet:251615Pilomyxoid astrocytoma
BRAFOrphanet:389Langerhans cell histiocytosis
BRAFOrphanet:500Noonan syndrome with multiple lentigines
BRAFOrphanet:54595Craniopharyngioma
BRAFOrphanet:58017Classic hairy cell leukemia
BRAFOrphanet:626Large/giant congenital melanocytic nevus
BRAFOrphanet:648Noonan syndrome
BRAFOrphanet:840Syringocystadenoma papilliferum
BRAFOrphanet:96253Cushing disease
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
MGMTOrphanet:251576Gliosarcoma
MGMTOrphanet:251579Giant cell glioblastoma
MGMTOrphanet:618Familial melanoma
PDGFRAOrphanet:168940Chronic eosinophilic leukemia
PDGFRAOrphanet:168947Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRAOrphanet:199306Cleft lip/palate
PDGFRAOrphanet:314950Primary hypereosinophilic syndrome
PDGFRAOrphanet:44890Gastrointestinal stromal tumor
PDGFRAOrphanet:585877B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
TP53Orphanet:1333Familial pancreatic carcinoma
TP53Orphanet:145Hereditary breast and/or ovarian cancer syndrome
TP53Orphanet:1501Adrenocortical carcinoma
TP53Orphanet:210159Adult hepatocellular carcinoma
TP53Orphanet:251576Gliosarcoma
TP53Orphanet:251579Giant cell glioblastoma
TP53Orphanet:251899Choroid plexus carcinoma
TP53Orphanet:2807Papilloma of choroid plexus
TP53Orphanet:293199Pleomorphic rhabdomyosarcoma
TP53Orphanet:3318Essential thrombocythemia

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only7
multi_evidence4

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BRAFHGNC:1097ENSG00000157764P15056Serine/threonine-protein kinase B-rafcivic_evidence
EGFRHGNC:3236ENSG00000146648P00533Epidermal growth factor receptorcivic_evidence
H3-3AHGNC:4764ENSG00000163041P84243Histone H3.3civic_evidence
IDH1HGNC:5382ENSG00000138413O75874Isocitrate dehydrogenase [NADP] cytoplasmiccivic_evidence
IDH2HGNC:5383ENSG00000182054P48735Isocitrate dehydrogenase [NADP], mitochondrialcivic_evidence
MGMTHGNC:7059ENSG00000170430P16455Methylated-DNA–protein-cysteine methyltransferasecivic_evidence
PDGFRAHGNC:8803ENSG00000134853P16234Platelet-derived growth factor receptor alphacivic_evidence
TP53HGNC:11998ENSG00000141510P04637Cellular tumor antigen p53clinvar
APCHGNC:583ENSG00000134982P25054Adenomatous polyposis coli proteinclinvar
MSH2HGNC:7325ENSG00000095002P43246DNA mismatch repair protein Msh2clinvar
ATMHGNC:795ENSG00000149311Q13315Serine-protein kinase ATMclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
BRAFSerine/threonine-protein kinase B-rafProtein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
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.
H3-3AHistone H3.3Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes.
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.
MGMTMethylated-DNA–protein-cysteine methyltransferaseInvolved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA.
PDGFRAPlatelet-derived growth factor receptor alphaTyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
TP53Cellular tumor antigen p53Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
APCAdenomatous polyposis coli proteinTumor suppressor.
MSH2DNA mismatch repair protein Msh2Component of the post-replicative DNA mismatch repair system (MMR).
ATMSerine-protein kinase ATMSerine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.

Protein-family classification

Druggable: 7 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.64

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
Kinase410.1×0.002
Enzyme (other)33.3×0.115
Transcription factor10.8×0.987
Other/Unknown30.5×0.987

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BRAFKinaseyes2.7.10.2Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
EGFRKinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
H3-3AOther/UnknownnoHistone_H3/CENP-A, H2A/H2B/H3, Histone-fold
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
MGMTEnzyme (other)yes2.1.1.63MethylDNA_cys_MeTrfase_AS, MethylG_MeTrfase_N, MethylDNA_cys_MeTrfase_DNA-bd
PDGFRAKinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
TP53Transcription factornop53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
APCOther/UnknownnoArmadillo, APC_rpt, SAMP
MSH2Other/UnknownnoDNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
ATMKinaseyes2.7.11.1PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom

Expression context

Cohort genes with no expression data: 0.

11 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)11
unknown0

Top tissues across cohort

TissueCohort genes
ventricular zone3
calcaneal tendon2
colonic epithelium2
ganglionic eminence2
buccal mucosa cell1
gingiva1
gingival epithelium1
nipple1
monocyte1
adrenal tissue1
corpus epididymis1
jejunal mucosa1
apex of heart1
gastrocnemius1
hindlimb stylopod muscle1
endometrium epithelium1
liver1
right lobe of liver1
decidua1
synovial joint1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
BRAF265ubiquitousmarkerbuccal mucosa cell, colonic epithelium, calcaneal tendon
EGFR285ubiquitousmarkernipple, gingiva, gingival epithelium
H3-3A134ubiquitousmarkerganglionic eminence, monocyte, ventricular zone
IDH1294ubiquitousmarkercorpus epididymis, jejunal mucosa, adrenal tissue
IDH2292ubiquitousmarkerapex of heart, gastrocnemius, hindlimb stylopod muscle
MGMT261ubiquitousmarkerright lobe of liver, liver, endometrium epithelium
PDGFRA289ubiquitousmarkertibia, decidua, synovial joint
TP53223ubiquitousmarkerventricular zone, ganglionic eminence, tendon of biceps brachii
APC297ubiquitousmarkersubstantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus
MSH2278ubiquitousmarkersecondary oocyte, oocyte, ventricular zone
ATM286ubiquitousmarkercalcaneal tendon, colonic epithelium, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 12.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TP5322,736
EGFR18,421
BRAF7,394
ATM7,383
IDH15,464
PDGFRA5,186
IDH24,912
MSH24,537
APC2,903
MGMT2,853

Intra-cohort edges

ABSources
ATMMSH2string_interaction
ATMTP53biogrid_interaction, string_interaction
BRAFEGFRbiogrid_interaction
BRAFTP53string_interaction
EGFRIDH2biogrid_interaction
EGFRMGMTstring_interaction
EGFRPDGFRAintact
IDH1IDH2biogrid_interaction
IDH1MGMTstring_interaction
IDH1TP53string_interaction
IDH2MGMTstring_interaction
MGMTTP53string_interaction

Structural data

PDB: 11 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
EGFRP00533388
TP53P04637313
BRAFP15056131
H3-3AP84243103
IDH1O7587461
APCP2505431
MSH2P4324630
MGMTP1645523
PDGFRAP1623415
ATMQ1331514
IDH2P4873511

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 258. Enrichment computed across 11 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
TP53 Regulates Transcription of Caspase Activators and Caspases2173.0×0.006TP53, ATM
Stabilization of p532138.4×0.006TP53, ATM
Diseases of DNA repair2103.8×0.006MSH2, ATM
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release298.9×0.006TP53, ATM
Regulation of TP53 Activity through Methylation298.9×0.006TP53, ATM
TP53 Regulates Transcription of DNA Repair Genes349.4×0.006TP53, MSH2, ATM
DNA Repair326.9×0.006MGMT, MSH2, ATM
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate11038.2×0.012IDH1
APC truncation mutants are not K63 polyubiquitinated11038.2×0.012APC
MGMT-mediated DNA damage reversal11038.2×0.012MGMT
Imatinib-resistant PDGFR mutants11038.2×0.012PDGFRA
Sunitinib-resistant PDGFR mutants11038.2×0.012PDGFRA
Regorafenib-resistant PDGFR mutants11038.2×0.012PDGFRA
Sorafenib-resistant PDGFR mutants11038.2×0.012PDGFRA
PDGFR mutants bind TKIs11038.2×0.012PDGFRA
Loss of function of TP53 in cancer due to loss of tetramerization ability11038.2×0.012TP53
Regulation of TP53 Degradation253.2×0.012TP53, ATM
Ovarian tumor domain proteases250.6×0.012TP53, APC
Autodegradation of the E3 ubiquitin ligase COP1248.3×0.012TP53, ATM
RAF/MAP kinase cascade316.7×0.012BRAF, EGFR, PDGFRA
NADPH regeneration1519.1×0.020IDH1
Defective Mismatch Repair Associated With MSH31519.1×0.020MSH2
Defective Mismatch Repair Associated With MSH61519.1×0.020MSH2
Regulation of TP53 Expression1519.1×0.020TP53
DNA Damage/Telomere Stress Induced Senescence229.7×0.020TP53, ATM
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks226.6×0.024TP53, ATM
Defective Mismatch Repair Associated With MSH21346.1×0.025MSH2
NFE2L2 regulating TCA cycle genes1346.1×0.025IDH1
PLCG1 events in ERBB2 signaling1259.6×0.025EGFR
Mismatch Repair1259.6×0.025MSH2

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 termCohort genesFoldFDRSample cohort genes
glyoxylate cycle21532.0×1e-04IDH1, IDH2
determination of adult lifespan3117.8×3e-04TP53, MSH2, ATM
isocitrate metabolic process2612.8×5e-04IDH1, IDH2
negative regulation of glial cell proliferation2306.4×0.001TP53, IDH2
NADP+ metabolic process2278.6×0.001IDH1, IDH2
double-strand break repair355.4×0.001TP53, MSH2, ATM
positive regulation of cell migration422.4×0.001EGFR, APC, ATM, PDGFRA
replicative senescence2180.2×0.002TP53, ATM
2-oxoglutarate metabolic process2170.2×0.002IDH1, IDH2
response to X-ray2161.3×0.002TP53, MSH2
multicellular organism growth337.4×0.002TP53, H3-3A, ATM
positive regulation of peptidyl-serine phosphorylation2139.3×0.003BRAF, EGFR
cellular response to gamma radiation2109.4×0.004TP53, ATM
mitotic spindle assembly checkpoint signaling2102.1×0.004APC, ATM
tricarboxylic acid cycle292.8×0.004IDH1, IDH2
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator290.1×0.004TP53, MSH2
negative regulation of apoptotic process412.6×0.004BRAF, TP53, EGFR, MGMT
positive regulation of ERK1 and ERK2 cascade323.2×0.005BRAF, EGFR, PDGFRA
T cell differentiation in thymus274.7×0.006BRAF, TP53
cellular response to reactive oxygen species274.7×0.006ATM, PDGFRA
somitogenesis268.1×0.006TP53, ATM
DNA damage response, signal transduction by p53 class mediator265.2×0.006TP53, ATM
in utero embryonic development319.6×0.006TP53, MSH2, PDGFRA
somatic recombination of immunoglobulin genes involved in immune response11532.0×0.006MSH2
negative regulation of helicase activity11532.0×0.006TP53
regulation of phospholipid catabolic process11532.0×0.006IDH1
cellular response to actinomycin D11532.0×0.006TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator11532.0×0.006TP53
negative regulation of G1 to G0 transition11532.0×0.006TP53
negative regulation of cardiocyte differentiation11532.0×0.006EGFR

Therapeutics

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 8 · Phased (≥1): 8 · Undrugged: 3

Druggability breadth: 11 of 11 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
BRAFVEMURAFENIB
EGFRLEVODOPA
IDH1ENASIDENIB
IDH2ENASIDENIB
PDGFRAPONATINIB
TP53NITROFURANTOIN
ATMAMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
TP531964
EGFR1754
PDGFRA774
BRAF484
ATM354
IDH1104
IDH274
MGMT23
H3-3A00
APC00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
VEMURAFENIB4BRAF, EGFR
PONATINIB4BRAF, EGFR, PDGFRA
FEDRATINIB4BRAF, EGFR, PDGFRA
SORAFENIB4BRAF, EGFR, PDGFRA
DASATINIB ANHYDROUS4BRAF, EGFR
RUXOLITINIB4BRAF
INFIGRATINIB PHOSPHATE4BRAF, PDGFRA
INFIGRATINIB4BRAF, PDGFRA
REGORAFENIB4BRAF, PDGFRA
DABRAFENIB4BRAF
COBIMETINIB4BRAF
NILOTINIB4BRAF, PDGFRA
ABEMACICLIB4BRAF, EGFR
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF, PDGFRA
DASATINIB4BRAF, EGFR, PDGFRA
ERLOTINIB4BRAF, EGFR, PDGFRA
GEFITINIB4BRAF, EGFR
IMATINIB4BRAF, EGFR, PDGFRA
LEVODOPA4EGFR
CLOTRIMAZOLE4EGFR, TP53
ERLOTINIB HYDROCHLORIDE4EGFR
CISPLATIN4EGFR
AFATINIB4EGFR
CHROMIC CHLORIDE4EGFR
BACITRACIN4EGFR
ZINC CHLORIDE4EGFR
LAPATINIB DITOSYLATE4EGFR
AXITINIB4EGFR, PDGFRA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

SymbolAssaysType breakdown
EGFR6,531Binding:6211, Functional:173, ADMET:138, Toxicity:9
BRAF1,442Binding:1400, Functional:37, ADMET:5
PDGFRA1,172Binding:1160, Functional:8, ADMET:4
TP53869Binding:775, ADMET:83, Functional:10, Toxicity:1
IDH1488Binding:475, Functional:12, ADMET:1
ATM240Binding:233, Functional:5, ADMET:2
MGMT86Binding:84, ADMET:2
IDH284Binding:84
APC24Binding:24
MSH29Binding:9
H3-3A6Binding:6

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BRAF2.7.10.2, 2.7.11.1non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
EGFR2.7.10.1receptor protein-tyrosine kinase
IDH11.1.1.42isocitrate dehydrogenase (NADP+)
IDH21.1.1.42isocitrate dehydrogenase (NADP+)
MGMT2.1.1.63methylated-DNA-[protein]-cysteine S-methyltransferase
PDGFRA2.7.10.1receptor protein-tyrosine kinase
ATM2.7.11.1non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BRAF1,442
EGFR6,531
IDH1488
PDGFRA1,172
TP53869
ATM240

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).

Drug repurposing candidates

27 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)
PONATINIB4BRAF, EGFR, PDGFRA
FEDRATINIB4BRAF, EGFR, PDGFRA
SORAFENIB4BRAF, EGFR, PDGFRA
DASATINIB ANHYDROUS4BRAF, EGFR
RUXOLITINIB4BRAF
INFIGRATINIB PHOSPHATE4BRAF, PDGFRA
INFIGRATINIB4BRAF, PDGFRA
REGORAFENIB4BRAF, PDGFRA
COBIMETINIB4BRAF
NILOTINIB4BRAF, PDGFRA
ABEMACICLIB4BRAF, EGFR
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF, PDGFRA
DASATINIB4BRAF, EGFR, PDGFRA
ERLOTINIB4BRAF, EGFR, PDGFRA
GEFITINIB4BRAF, EGFR
IMATINIB4BRAF, EGFR, PDGFRA
LEVODOPA4EGFR
CLOTRIMAZOLE4EGFR, TP53
ERLOTINIB HYDROCHLORIDE4EGFR
CISPLATIN4EGFR
CHROMIC CHLORIDE4EGFR
BACITRACIN4EGFR
ZINC CHLORIDE4EGFR
LAPATINIB DITOSYLATE4EGFR
AXITINIB4EGFR, PDGFRA

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)7BRAF, EGFR, IDH1, IDH2, PDGFRA, TP53, ATM
BPhased (≥1) drug, not yet approved1MGMT
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug3H3-3A, APC, MSH2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
H3-3A6—
APC24—
MSH29—

Clinical trials & evidence

Clinical trials

Clinical trials: 963.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified392
PHASE1217
PHASE2182
PHASE1/PHASE287
EARLY_PHASE153
PHASE319
PHASE2/PHASE38
PHASE45

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03048084PHASE4RECRUITINGSeizure Treatment in Glioma
NCT03340506PHASE4RECRUITINGDabrafenib and/or Trametinib Rollover Study
NCT07486713PHASE4RECRUITINGOlutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT04650204PHASE4TERMINATEDPerampanel for the Reduction of Seizure Frequency in Patients With High-grade Glioma and Focal Epilepsy
NCT06625047PHASE4COMPLETEDComparing Telehealth and In-person Assessments in Glioma Patients Receiving Oral Chemotherapy
NCT04164901PHASE3ACTIVE_NOT_RECRUITINGStudy of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
NCT05271240PHASE3RECRUITINGRepeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed GBM
NCT05303519PHASE3RECRUITINGSIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance)
NCT05512403PHASE3RECRUITINGEvaluation of Diagnostic Performances of 18F-FDOPA PET KInetics
NCT05580562PHASE3RECRUITINGONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study)
NCT05768178PHASE2/PHASE3RECRUITINGDETERMINE Trial Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.
NCT05770544PHASE2/PHASE3RECRUITINGDETERMINE Trial Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage/Young Adult Patients With ROS1 Gene Fusion-Positive Cancers.
NCT06330337PHASE3RECRUITINGEffect of Electroacupuncture Combined With Paclitaxel Clinical Efficacy of Patients With Recurrence of High-grade Glioma
NCT06496971PHASE3RECRUITINGA Prospective Pivotal Study to Evaluate the Efficacy and Safety of Avastin® Bevacizumab (BEV) With or Without Microbubble-mediated Focused Ultrasound (FUS-MB) Using NaviFUS System in Recurrent Glioblastoma Multiforme Patients
NCT06750458PHASE3NOT_YET_RECRUITINGDapagliflozin Versus Dexamethasone Role in Pre-operative Management of Non- Diabetic Brain Tumor Patients
NCT06888817PHASE3RECRUITINGBevacizumab Versus Corticosteroids as First-line Treatment in Patients With Symptomatic Cerebral Radiation Necrosis After Radiation for High-grade Glioma or Brain Metastases
NCT06988475PHASE2/PHASE3RECRUITINGDETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations
NCT07440290PHASE2/PHASE3NOT_YET_RECRUITINGDETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positive Cancers.
NCT00045968PHASE3UNKNOWNStudy of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer
NCT00256425PHASE3UNKNOWNCognitive Rehabilitation of Glioma Patients
NCT01167322PHASE3COMPLETEDStudy of NPC-07 for Fluorescence-guided Resection of Malignant Gliomas
NCT01460706PHASE2/PHASE3COMPLETEDImaging Malignant Glioma With 68Ga-DOTATOC PET/CT
NCT01479686PHASE3COMPLETEDiMRI Guided Resection in Cerebral Glioma Surgery
NCT01502280PHASE3COMPLETEDFluorescence-guided Surgery for Low- and High-grade Gliomas
NCT01655927PHASE3UNKNOWNEfficacy of Tranexamic Acid in Brain Tumor Resections
NCT01961934PHASE2/PHASE3WITHDRAWNC11-Sodium Acetate PET/CT Imaging Evaluation in Brain Glioma, Post Therapy Necrosis and Pseudo-progression
NCT02363075PHASE3UNKNOWNDexamfetamine Sulphate in Patients With Glioma Suffering From Severe Asthenia
NCT02678975PHASE2/PHASE3COMPLETEDDisulfiram in Recurrent Glioblastoma
NCT02879682PHASE2/PHASE3COMPLETEDnTMS for Motor Mapping of Rolandic Lesions
NCT02892708PHASE3COMPLETEDImpact of Surgery on the Treatment of Supratentorial Malignant Gliomas in Subjects Aged 70 and Over
NCT03149575PHASE3TERMINATEDVAL-083 Phase 3 Study in Temozolomide-Avastin (Bevacizumab) Recurrent GBM
NCT03722355PHASE3COMPLETEDHyperfractionated RT With BCNU Versus Conventional RT With BCNU for Supratentorial Malignant Glioma
NCT01906385PHASE1/PHASE2RECRUITINGMaximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioma (ReSPECT)
NCT02465060PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT02800486PHASE2RECRUITINGSuper Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA
NCT03155620PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03180502PHASE2ACTIVE_NOT_RECRUITINGProton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients With IDH Mutant Grade II or III Glioma
NCT03210714PHASE2ACTIVE_NOT_RECRUITINGErdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03212274PHASE2ACTIVE_NOT_RECRUITINGOlaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations
NCT03212742PHASE1/PHASE2ACTIVE_NOT_RECRUITINGPhase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
LAROTRECTINIB47
DABRAFENIB46
LAPATINIB46
LOMUSTINE46
IVOSIDENIB45
TRAMETINIB45
VALACYCLOVIR45
VALPROIC ACID45
VORASIDENIB45
AMINOLEVULINIC ACID44
ERDAFITINIB44
AFATINIB43
EFLORNITHINE43
RETIFANLIMAB43
SELUMETINIB43
VANDETANIB43
VEMURAFENIB43
BINIMETINIB42
CARMUSTINE42
CEMIPLIMAB42
CRIZOTINIB42
ENSARTINIB42
ENTRECTINIB42
FLUORODOPA F 1842
LACOSAMIDE42
OLUTASIDENIB42
PANOBINOSTAT42
PERAMPANEL42
RIBOCICLIB42
SELINEXOR42

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 25 predictive associations from 27 curated evidence items; also 5 prognostic, 3 diagnostic, 2 oncogenic.

Molecular subtypeTherapyEffectLevelCIViC
IDH2 Mutation OR IDH1 MutationVorasidenibSensitivity/ResponseCIViC AEID11708
BRAF V600ESelumetinibSensitivity/ResponseCIViC BEID2145 +1
H3-3A K28MDordaviproneSensitivity/ResponseCIViC BEID7601
IDH1 R132Bevacizumab + SunitinibSensitivity/ResponseCIViC BEID2020
IDH1 R132BevacizumabSensitivity/ResponseCIViC BEID2330
IDH1 R132SafusidenibSensitivity/ResponseCIViC BEID7448
IDH1 R132SBevacizumabSensitivity/ResponseCIViC BEID2339
MGMT UnderexpressionTemozolomideSensitivity/ResponseCIViC BEID2901
BRAF V600EVemurafenibSensitivity/ResponseCIViC CEID12719 +1
EGFR Amplification OR EGFR VIIIOsimertinibSensitivity/ResponseCIViC CEID12694
EML4::ALK FusionEntrectinibSensitivity/ResponseCIViC CEID12607
EML4::NTRK3 FusionLarotrectinibSensitivity/ResponseCIViC CEID11100
ETV6::NTRK3 FusionLarotrectinibSensitivity/ResponseCIViC CEID10931
TPR::NTRK1 FusionEntrectinibSensitivity/ResponseCIViC CEID11851
EGFR A289VErlotinibSensitivity/ResponseCIViC DEID4188
EGFR L858RErlotinibSensitivity/ResponseCIViC DEID4295
EGFR L861QErlotinibSensitivity/ResponseCIViC DEID4299
EGFR OverexpressionGefitinib + Radiation TherapySensitivity/ResponseCIViC DEID7803
EGFR R108KErlotinibSensitivity/ResponseCIViC DEID4186
EGFR T263PErlotinibSensitivity/ResponseCIViC DEID4187
EGFR VIIIErlotinibSensitivity/ResponseCIViC DEID4500
HOXC10 OverexpressionBevacizumabSensitivity/ResponseCIViC DEID9949
HSP90B1 OverexpressionOnalespib + TemozolomideSensitivity/ResponseCIViC DEID10153
IDH1 R132CAGI-5198Sensitivity/ResponseCIViC DEID2329
PDGFRA OverexpressionDasatinibSensitivity/ResponseCIViC DEID7934

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 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmeddramedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot