◎ Sugi Atlas

Atlas / Disease / Astrocytoma (excluding glioblastoma)

Astrocytoma (excluding glioblastoma)

disease
On this page

Also known as astrocytoma

Summary

Astrocytoma (excluding glioblastoma) (MONDO:0019781) is a disease (an umbrella term covering 5 Mondo subtypes) with 11 cohort genes (548 GWAS associations across 6 studies) and 96 clinical trials. The dominant Reactome pathway is Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (3 cohort genes). Top therapeutic interventions include imatinib, temozolomide, and aminolevulinic acid.

At a glance

  • Umbrella term: 5 Mondo subtypes
  • Cohort genes: 11
  • GWAS associations: 548
  • ClinVar variants: 11
  • Clinical trials: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameastrocytoma (excluding glioblastoma)
Mondo IDMONDO:0019781
EFOEFO:0000272
MeSHD001254
NCITC60781
SNOMED CT147101000119108
UMLSC0004114
MedGen438
GARD0025146
Is cancer (heuristic)no

Also known as: astrocytoma

Data availability: 11 ClinVar variants · 548 GWAS associations (6 studies) · 209 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › nervous system neoplasm › neuroepithelial neoplasm › glioma › astrocytic tumor › astrocytoma (excluding glioblastoma)

Related subtypes (7): adult astrocytic tumor, childhood astrocytic tumor, gliofibroma, high grade astrocytic tumor, low grade astrocytic tumor, anaplastic pleomorphic xanthoastrocytoma, infant-type hemispheric glioma

Subtypes (5): cauda equina intradural extramedullary astrocytoma, spinal cord astrocytoma, anaplastic astrocytoma, low-grade astrocytoma, brain astrocytoma

Genetics & variants

GWAS landscape

548 GWAS associations across 6 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1470220927e-10CYP2J2 - RN7SL475P?5.47
rs1892255272e-09AP5M1 - NAA30?12.43
rs1427215532e-09FGGY?5.48
chr9:219993283e-09?
rs28117133e-09CDKN2B-AS1?1.3
rs784572614e-09LINC02220 - RPS23P5?3.08
rs1903308806e-09SLC14A2?12.62
rs799094031e-08STRBP - CRB2?3.14
rs1402633311e-08OR5C1 - PDCL?11.36
rs5343826661e-08MAPRE1P2 - RPL31P31?7.12
rs1176095792e-08TCERG1L - LINC01164?11.26
rs788812372e-08PDZRN4?7.56
rs1509127273e-08CNTN1?7.59
rs1444597623e-08RABGAP1?9.43
rs1465296533e-08RCSD1?10.47
rs5736873e-08CDKN2B-AS1?1.31
rs31015224e-08ACBD3?2.26
rs5385592585e-08HSPE1P14 - RPS12P15?10.78
rs21834285e-08GPC6?0.19
rs1931990716e-08TPT1P9 - LINC02578?3.72
rs1508907447e-08PGBD4P8 - LINC02778?4.7
rs1448995457e-08CNTN1?6.36
rs792743307e-08PDZRN4?7.23
rs1826434499e-08ZNF148?7.31
rs1841685999e-08OLA1?5.21
chr8:1032982281e-07?10.14
rs1827264611e-07MYLKP2 - OR7E130P?8.84
rs1869485191e-07LINC02778 - LINC01748?8.14
rs619034681e-07NTM?2.68
rs1162640572e-07TENM2?3.75

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90296466Foss-Skiftesvik J20231,5417,183Multi-ancestry genome-wide association study of 4,069 children with glioma identifies 9p21.3 risk locus.
GCST90296476Foss-Skiftesvik J20231,5417,183Multi-ancestry genome-wide association study of 4,069 children with glioma identifies 9p21.3 risk locus.
GCST90296467Foss-Skiftesvik J20231,1477,183Multi-ancestry genome-wide association study of 4,069 children with glioma identifies 9p21.3 risk locus.
GCST90296477Foss-Skiftesvik J20231,1477,183Multi-ancestry genome-wide association study of 4,069 children with glioma identifies 9p21.3 risk locus.
GCST90296468Foss-Skiftesvik J20232807,183Multi-ancestry genome-wide association study of 4,069 children with glioma identifies 9p21.3 risk locus.
GCST90296478Foss-Skiftesvik J20232807,183Multi-ancestry genome-wide association study of 4,069 children with glioma identifies 9p21.3 risk locus.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR1
Tier 3: regulatory0
Tier 4: intronic/intergenic49

MAF distribution

BucketVariants
common (>=0.05)15
low_freq (0.01-0.05)0
rare (<0.01)0
unknown35

Functional consequences

ConsequenceCount
intron_variant32
intergenic_variant15
unknown2
3_prime_UTR_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs147022092159969208G>Aintergenic_variantCYP2J2 - RN7SL475P7e-10Tier 4: intronic/intergenic
rs1892255271457378883G>Aintron_variantAP5M1 - NAA302e-09Tier 4: intronic/intergenic
rs142721553159773132C>Tintron_variantFGGY2e-09Tier 4: intronic/intergenic
chr9:219993283e-09Tier 4: intronic/intergenic
rs2811713921999329G>A,T0.05intron_variantCDKN2B-AS13e-09Tier 4: intronic/intergenic
rs78457261513206067T>G0.05intergenic_variantLINC02220 - RPS23P54e-09Tier 4: intronic/intergenic
rs1903308801845349873G>Aintron_variantSLC14A26e-09Tier 4: intronic/intergenic
rs799094039123292889C>T0.05intergenic_variantSTRBP - CRB21e-08Tier 4: intronic/intergenic
rs1402633319122792635G>Aintergenic_variantOR5C1 - PDCL1e-08Tier 4: intronic/intergenic
rs534382666433735687G>A,Tintergenic_variantMAPRE1P2 - RPL31P311e-08Tier 4: intronic/intergenic
rs11760957910131482444A>G,Tintergenic_variantTCERG1L - LINC011642e-08Tier 4: intronic/intergenic
rs788812371241288171G>A,Tintron_variantPDZRN42e-08Tier 4: intronic/intergenic
rs1509127271240938934C>A,Tintron_variantCNTN13e-08Tier 4: intronic/intergenic
rs1444597629123055711G>A,Tintron_variantRABGAP13e-08Tier 4: intronic/intergenic
rs1465296531167668816G>Aintron_variantRCSD13e-08Tier 4: intronic/intergenic
rs573687922011643G>A0.05intron_variantCDKN2B-AS13e-08Tier 4: intronic/intergenic
rs31015221226178209T>C0.05intron_variantACBD34e-08Tier 4: intronic/intergenic
rs5385592588102473296A>Cintron_variantHSPE1P14 - RPS12P155e-08Tier 4: intronic/intergenic
rs21834281393881124T>A,C,Gintron_variantGPC65e-08Tier 4: intronic/intergenic
rs1931990719118627326A>G0.05intergenic_variantTPT1P9 - LINC025786e-08Tier 4: intronic/intergenic
rs150890744160112660G>A,Tintergenic_variantPGBD4P8 - LINC027787e-08Tier 4: intronic/intergenic
rs1448995451240820597G>A,Tintron_variantCNTN17e-08Tier 4: intronic/intergenic
rs792743301241536465G>A,Tintron_variantPDZRN47e-08Tier 4: intronic/intergenic
rs1826434493125314666T>Cintron_variantZNF1489e-08Tier 4: intronic/intergenic
rs1841685992174174068C>Tintron_variantOLA19e-08Tier 4: intronic/intergenic
chr8:1032982281e-07Tier 4: intronic/intergenic
rs1827264613125692111C>Tintron_variantMYLKP2 - OR7E130P1e-07Tier 4: intronic/intergenic
rs186948519160220115A>C,Gintergenic_variantLINC02778 - LINC017481e-07Tier 4: intronic/intergenic
rs6190346811131990671A>G0.05intron_variantNTM1e-07Tier 4: intronic/intergenic
rs1162640575167934496A>C,Tintron_variantTENM22e-07Tier 4: intronic/intergenic

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

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

ClinVarVariant (HGVS)GeneClassificationReview
128042NM_007194.4(CHEK2):c.1100del (p.Thr367fs)CHEK2Pathogeniccriteria provided, multiple submitters, no conflicts
504473NC_000014.9:g.38411139_38421941dupLikely pathogeniccriteria provided, single submitter
1698836NM_004656.4(BAP1):c.437G>C (p.Arg146Thr)BAP1Likely pathogeniccriteria provided, multiple submitters, no conflicts
434329NM_006015.6(ARID1A):c.48GCC[6] (p.Pro21dup)ARID1AConflicting classifications of pathogenicitycriteria provided, conflicting classifications
496813NM_001374828.1(ARID1B):c.1000T>G (p.Cys334Gly)ARID1BUncertain significancecriteria provided, single submitter
1435621NM_001384732.1(CPLANE1):c.356A>G (p.Tyr119Cys)CPLANE1Uncertain significancecriteria provided, multiple submitters, no conflicts
503605NM_001281766.3(EPHA5):c.1043A>G (p.Asp348Gly)EPHA5Uncertain significancecriteria provided, single submitter
2576980NM_023110.3(FGFR1):c.1179_2378dup (p.Val429_Asn763delinsGluSerArgTrpGlyIleCysThrLeuSerThrThrSerLeuSerGlyProLeuMetProCysProLeuHisCysProTer)FGFR1Uncertain significanceno assertion criteria provided
503606NM_003482.4(KMT2D):c.15876G>C (p.Glu5292Asp)KMT2DUncertain significancecriteria provided, single submitter
142324NM_000546.6(TP53):c.848G>A (p.Arg283His)TP53Uncertain significancecriteria provided, multiple submitters, no conflicts
523362NM_000368.5(TSC1):c.359T>C (p.Leu120Pro)TSC1Uncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 60 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
ARID1AOrphanet:1465Coffin-Siris syndrome
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
TP53Orphanet:524Li-Fraumeni syndrome
TP53Orphanet:52688Myelodysplastic syndrome
TP53Orphanet:585909B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53Orphanet:667662Breast implant-associated anaplastic large cell lymphoma
TP53Orphanet:668Osteosarcoma
TP53Orphanet:67038B-cell chronic lymphocytic leukemia
TP53Orphanet:70573Small cell lung cancer
TP53Orphanet:96253Cushing disease
TP53Orphanet:99756Alveolar rhabdomyosarcoma
TP53Orphanet:99757Embryonal rhabdomyosarcoma
TSC1Orphanet:210159Adult hepatocellular carcinoma
TSC1Orphanet:269008Isolated focal cortical dysplasia type IIb
TSC1Orphanet:538Lymphangioleiomyomatosis
TSC1Orphanet:805Tuberous sclerosis complex
CHEK2Orphanet:1331Familial prostate cancer
CHEK2Orphanet:145Hereditary breast and/or ovarian cancer syndrome
CHEK2Orphanet:440437Familial colorectal cancer Type X
CHEK2Orphanet:524Li-Fraumeni syndrome
CHEK2Orphanet:668Osteosarcoma
ARID1BOrphanet:1465Coffin-Siris syndrome
ARID1BOrphanet:2510566q25.2q25.3 microdeletion syndrome
CPLANE1Orphanet:2754Orofaciodigital syndrome type 6
CPLANE1Orphanet:475Isolated Joubert syndrome
CPLANE1Orphanet:65684Monomelic amyotrophy
FGFR1Orphanet:168953Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1Orphanet:2117Hartsfield syndrome
FGFR1Orphanet:220386Semilobar holoprosencephaly
FGFR1Orphanet:2396Encephalocraniocutaneous lipomatosis
FGFR1Orphanet:251576Gliosarcoma
FGFR1Orphanet:251579Giant cell glioblastoma
FGFR1Orphanet:251615Pilomyxoid astrocytoma
FGFR1Orphanet:2645Osteoglosphonic dysplasia
FGFR1Orphanet:280200Microform holoprosencephaly
FGFR1Orphanet:314950Primary hypereosinophilic syndrome
FGFR1Orphanet:3157Septo-optic dysplasia spectrum
FGFR1Orphanet:3366Non-syndromic metopic craniosynostosis
FGFR1Orphanet:432Normosmic congenital hypogonadotropic hypogonadism
FGFR1Orphanet:478Kallmann syndrome
FGFR1Orphanet:93258Pfeiffer syndrome type 1

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence11

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
ARID1AHGNC:11110ENSG00000117713O14497AT-rich interactive domain-containing protein 1Aclinvar
TP53HGNC:11998ENSG00000141510P04637Cellular tumor antigen p53clinvar
TSC1HGNC:12362ENSG00000165699Q92574Hamartinclinvar
CHEK2HGNC:16627ENSG00000183765O96017Serine/threonine-protein kinase Chk2clinvar
ARID1BHGNC:18040ENSG00000049618Q8NFD5AT-rich interactive domain-containing protein 1Bclinvar
CPLANE1HGNC:25801ENSG00000197603Q9H799Ciliogenesis and planar polarity effector 1clinvar
EPHA5HGNC:3389ENSG00000145242P54756Ephrin type-A receptor 5clinvar
FGFR1HGNC:3688ENSG00000077782P11362Fibroblast growth factor receptor 1clinvar
KMT2DHGNC:7133ENSG00000167548O14686Histone-lysine N-methyltransferase 2Dclinvar
MAGI1HGNC:946ENSG00000151276Q96QZ7Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1clinvar
BAP1HGNC:950ENSG00000163930Q92560Ubiquitin carboxyl-terminal hydrolase BAP1clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
ARID1AAT-rich interactive domain-containing protein 1AInvolved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
TP53Cellular tumor antigen p53Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TSC1HamartinNon-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolec…
CHEK2Serine/threonine-protein kinase Chk2Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.
ARID1BAT-rich interactive domain-containing protein 1BInvolved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
CPLANE1Ciliogenesis and planar polarity effector 1Involved in ciliogenesis.
EPHA5Ephrin type-A receptor 5Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
FGFR1Fibroblast growth factor receptor 1Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
KMT2DHistone-lysine N-methyltransferase 2DHistone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4).
MAGI1Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1Plays a role in coupling actin fibers to cell junctions in endothelial cells, via its interaction with AMOTL2 and CDH5.
BAP1Ubiquitin carboxyl-terminal hydrolase BAP1Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1.

Protein-family classification

Druggable: 5 · Difficult: 3 · Unknown: 3 · Druggable fraction: 0.45

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
Protease13.3×0.601
Scaffold/PPI11.6×0.601
Transcription factor21.5×0.601
Other/Unknown30.5×0.987

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
ARID1AOther/UnknownnoARID_dom, ARM-like, ARM-type_fold
TP53Transcription factornop53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TSC1Other/UnknownnoHamartin
CHEK2Kinaseyes2.7.11.1FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
ARID1BOther/UnknownnoARID_dom, BAF250/Osa, BAF250_C
CPLANE1Scaffold/PPInoCPLANE1, WD40_repeat_dom_sf
EPHA5Kinaseyes2.7.10.1Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
FGFR1Kinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
KMT2DTranscription factornoSET_dom, Znf_RING, Znf_PHD
MAGI1KinaseyesWW_dom, PDZ, Guanylate_kin-like_dom
BAP1Proteaseyes3.4.19.12Peptidase_C12_UCH, Peptidase_C12_UCH_sf, Papain-like_cys_pep_sf

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 zone4
sural nerve4
bone marrow cell2
ganglionic eminence2
male germ line stem cell (sensu Vertebrata) in testis2
calcaneal tendon2
buccal mucosa cell2
embryo1
tendon of biceps brachii1
gluteal muscle1
lateral globus pallidus1
substantia nigra pars compacta1
lower esophagus mucosa1
primordial germ cell in gonad1
colonic epithelium1
cortical plate1
stromal cell of endometrium1
medial globus pallidus1
corpus callosum1
left testis1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
ARID1A286ubiquitousmarkerbone marrow cell, ventricular zone, embryo
TP53223ubiquitousmarkerventricular zone, ganglionic eminence, tendon of biceps brachii
TSC1297ubiquitousmarkersubstantia nigra pars compacta, gluteal muscle, lateral globus pallidus
CHEK2183ubiquitousmarkerprimordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis
ARID1B256ubiquitousmarkerbone marrow cell, colonic epithelium, sural nerve
CPLANE1195ubiquitousmarkersural nerve, calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis
EPHA5142broadmarkercortical plate, ganglionic eminence, ventricular zone
FGFR1292ubiquitousmarkerbuccal mucosa cell, stromal cell of endometrium, calcaneal tendon
KMT2D272ubiquitousmarkerbuccal mucosa cell, medial globus pallidus, sural nerve
MAGI1133ubiquitousmarkerventricular zone, sural nerve, corpus callosum
BAP1253ubiquitousmarkerleft testis, right testis, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TP5322,736
FGFR15,693
TSC15,445
CHEK24,795
ARID1A3,476
BAP13,373
KMT2D3,223
EPHA52,566
ARID1B2,131
MAGI12,043

Intra-cohort edges

ABSources
ARID1AARID1Bbiogrid_interaction, string_interaction
ARID1AKMT2Dstring_interaction
CHEK2TP53intact, string_interaction
KMT2DTP53string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TP53P04637313
FGFR1P1136283
CHEK2O9601738
MAGI1Q96QZ716
KMT2DO1468611
ARID1AO144977
TSC1Q925745
BAP1Q925604
ARID1BQ8NFD52
EPHA5P547562

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
CPLANE1Q9H799

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 118. 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.

PathwayCohort genesFoldFDRSample cohort genes
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks348.8×0.001TP53, CHEK2, BAP1
Transcriptional regulation by RUNX1348.8×0.001ARID1A, ARID1B, KMT2D
Stabilization of p532169.2×0.002TP53, CHEK2
Formation of the canonical BAF (cBAF) complex2141.0×0.002ARID1A, ARID1B
Regulation of TP53 Activity through Methylation2120.8×0.003TP53, CHEK2
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)2101.5×0.003ARID1A, ARID1B
Chromatin organization327.2×0.003ARID1A, ARID1B, KMT2D
Chromatin modifying enzymes324.1×0.003ARID1A, ARID1B, KMT2D
Epigenetic regulation of gene expression323.8×0.003ARID1A, ARID1B, KMT2D
Regulation of endogenous retroelements281.9×0.003ARID1A, ARID1B
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known266.8×0.004ARID1A, ARID1B
Regulation of TP53 Degradation265.1×0.004TP53, CHEK2
Regulation of MITF-M-dependent genes involved in pigmentation259.0×0.004ARID1A, ARID1B
Loss of function of TP53 in cancer due to loss of tetramerization ability11268.9×0.007TP53
MITF-M-dependent gene expression240.3×0.008ARID1A, ARID1B
Signaling by FGFR1 amplification mutants1634.4×0.011FGFR1
Regulation of TP53 Expression1634.4×0.011TP53
RMTs methylate histone arginines232.5×0.011ARID1A, ARID1B
TP53 Regulates Metabolic Genes228.8×0.013TP53, TSC1
G2/M DNA damage checkpoint226.7×0.013TP53, CHEK2
Regulation of TP53 Activity through Phosphorylation226.2×0.013TP53, CHEK2
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)226.2×0.013ARID1A, ARID1B
MITF-M-regulated melanocyte development225.4×0.013ARID1A, ARID1B
FGFR1c and Klotho ligand binding and activation1317.2×0.014FGFR1
Transcriptional activation of cell cycle inhibitor p211317.2×0.014TP53
Signaling by plasma membrane FGFR1 fusions1317.2×0.014FGFR1
Inhibition of TSC complex formation by AKT (PKB)1253.8×0.017TSC1
Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome1253.8×0.017KMT2D
Activation of NOXA and translocation to mitochondria1211.5×0.019TP53
RUNX3 regulates CDKN1A transcription1181.3×0.022TP53

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
transcription initiation-coupled chromatin remodeling3104.5×8e-04ARID1A, TP53, ARID1B
positive regulation of cell differentiation373.0×0.001ARID1A, ARID1B, FGFR1
thymocyte apoptotic process2255.3×0.002TP53, CHEK2
replicative senescence2180.2×0.004TP53, CHEK2
regulation of G0 to G1 transition2122.6×0.006ARID1A, ARID1B
cellular response to gamma radiation2109.4×0.006TP53, CHEK2
regulation of nucleotide-excision repair2109.4×0.006ARID1A, ARID1B
regulation of mitotic metaphase/anaphase transition290.1×0.007ARID1A, ARID1B
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator290.1×0.007TP53, CHEK2
thrombocyte differentiation11532.0×0.007BAP1
nucleate erythrocyte differentiation11532.0×0.007BAP1
negative regulation of helicase activity11532.0×0.007TP53
cellular response to actinomycin D11532.0×0.007TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator11532.0×0.007TP53
negative regulation of G1 to G0 transition11532.0×0.007TP53
beta-catenin-TCF complex assembly11532.0×0.007KMT2D
positive regulation of T cell differentiation282.8×0.007ARID1A, ARID1B
positive regulation of myoblast differentiation266.6×0.007ARID1A, ARID1B
DNA damage response, signal transduction by p53 class mediator265.2×0.007TP53, CHEK2
positive regulation of double-strand break repair262.5×0.007ARID1A, ARID1B
stem cell proliferation256.7×0.007TP53, FGFR1
regulation of G1/S transition of mitotic cell cycle255.7×0.007ARID1A, ARID1B
regulation of cell cycle320.3×0.007TP53, TSC1, BAP1
in utero embryonic development319.6×0.007TP53, FGFR1, BAP1
protein stabilization318.2×0.007TP53, TSC1, CHEK2
positive regulation of DNA-templated transcription410.2×0.007ARID1A, TP53, CHEK2, ARID1B
heterochromatin formation246.4×0.009KMT2D, BAP1
cellular response to xenobiotic stimulus243.8×0.009TP53, CHEK2
positive regulation of mitochondrial membrane permeability1766.0×0.009TP53
vitamin D3 metabolic process1766.0×0.009FGFR1

Therapeutics

Drugs indicated for this disease

3 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
CarmustineApproved (phase 4)
EverolimusApproved (phase 4)
VorasidenibApproved (phase 4)
CarboplatinPhase 3 (in late-stage trials)
HydroxyureaPhase 3 (in late-stage trials)
TemozolomidePhase 3 (in late-stage trials)
Tranexamic AcidPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Atezolizumab, Bevacizumab, Cilengitide, Doxorubicin, Etoposide, Influenza Virus Vaccine, Irinotecan, PEGINTERFERON ALFA-2B, Tetanus Toxoid, Tipifarnib, Tislelizumab, Tocilizumab.

Drug target analysis

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

Druggability breadth: 8 of 11 evidence-associated genes (73%) 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
TP53NITROFURANTOIN
CHEK2NERATINIB
EPHA5PONATINIB
FGFR1PONATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
TP531964
FGFR1934
EPHA5354
CHEK2304
ARID1A00
TSC100
ARID1B00
CPLANE100
KMT2D00
MAGI100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
NITROFURANTOIN4TP53
DIOSMIN4TP53
VERTEPORFIN4TP53
CANDESARTAN CILEXETIL4TP53
DIENESTROL4TP53
CLOTRIMAZOLE4TP53
COLCHICINE4TP53
NABUMETONE4TP53
SALMETEROL XINAFOATE4TP53
AMIODARONE HYDROCHLORIDE4TP53
FURAZOLIDONE4TP53
AMOXAPINE4TP53
RALOXIFENE HYDROCHLORIDE4TP53
NICARDIPINE HYDROCHLORIDE4TP53
SULCONAZOLE NITRATE4TP53
PYRITHIONE ZINC4TP53
LACTIC ACID4TP53
OXYMETHOLONE4TP53
CHLOROXINE4TP53
PROPIOLACTONE4TP53
CLOMIPRAMINE HYDROCHLORIDE4TP53
PHENYL AMINOSALICYLATE4TP53
THIORIDAZINE HYDROCHLORIDE4TP53
AMITRIPTYLINE HYDROCHLORIDE4TP53
ETHOPROPAZINE HYDROCHLORIDE4TP53
MECHLORETHAMINE HYDROCHLORIDE4TP53
ECONAZOLE NITRATE4TP53
TRIFLUPROMAZINE HYDROCHLORIDE4TP53
PROCHLORPERAZINE EDISYLATE4TP53
DEQUALINIUM CHLORIDE4TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
FGFR11,465Binding:1428, Functional:24, ADMET:13
TP53869Binding:775, ADMET:83, Functional:10, Toxicity:1
CHEK2690Binding:687, Functional:2, ADMET:1
EPHA5243Binding:243
KMT2D11Binding:11
ARID1A6Binding:6
BAP15Binding:4, Functional:1
MAGI14Binding:4

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CHEK22.7.11.1non-specific serine/threonine protein kinase
EPHA52.7.10.1receptor protein-tyrosine kinase
FGFR12.7.10.1receptor protein-tyrosine kinase
BAP13.4.19.12ubiquitinyl hydrolase 1

Cohort genes with high screening signal

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

SymbolChEMBL assays
TP53869
CHEK2690
EPHA5243
FGFR11,465

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

30 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)
NITROFURANTOIN4TP53
DIOSMIN4TP53
VERTEPORFIN4TP53
CANDESARTAN CILEXETIL4TP53
DIENESTROL4TP53
CLOTRIMAZOLE4TP53
COLCHICINE4TP53
NABUMETONE4TP53
SALMETEROL XINAFOATE4TP53
AMIODARONE HYDROCHLORIDE4TP53
FURAZOLIDONE4TP53
AMOXAPINE4TP53
RALOXIFENE HYDROCHLORIDE4TP53
NICARDIPINE HYDROCHLORIDE4TP53
SULCONAZOLE NITRATE4TP53
PYRITHIONE ZINC4TP53
LACTIC ACID4TP53
OXYMETHOLONE4TP53
CHLOROXINE4TP53
PROPIOLACTONE4TP53
CLOMIPRAMINE HYDROCHLORIDE4TP53
PHENYL AMINOSALICYLATE4TP53
THIORIDAZINE HYDROCHLORIDE4TP53
AMITRIPTYLINE HYDROCHLORIDE4TP53
ETHOPROPAZINE HYDROCHLORIDE4TP53
MECHLORETHAMINE HYDROCHLORIDE4TP53
ECONAZOLE NITRATE4TP53
TRIFLUPROMAZINE HYDROCHLORIDE4TP53
PROCHLORPERAZINE EDISYLATE4TP53
DEQUALINIUM CHLORIDE4TP53

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)4TP53, CHEK2, EPHA5, FGFR1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug2MAGI1, BAP1
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug5ARID1A, TSC1, ARID1B, CPLANE1, KMT2D

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
ARID1A6—
TSC10—
ARID1B0—
CPLANE10—
KMT2D11—
MAGI14—
BAP15—

Clinical trials & evidence

Clinical trials

Clinical trials: 96.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified32
PHASE222
PHASE122
PHASE1/PHASE27
PHASE36
EARLY_PHASE16
PHASE41

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03975829PHASE4RECRUITINGPediatric Long-Term Follow-up and Rollover Study
NCT01649830PHASE3RECRUITINGEfficacy of Post-radiation Adjuvant Temozolomide Chemotherapy in Residue Low-grade Glioma
NCT00154375PHASE3COMPLETEDStudy of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
NCT00335075PHASE3COMPLETEDEfficacy and Safety of Temodal vs Semustine in Subjects With Recurrent Glioblastoma or Anaplastic Astrocytoma (Study P03644)
NCT00897377PHASE3TERMINATEDTreatment Strategy for Low-grade Gliomas
NCT01655927PHASE3UNKNOWNEfficacy of Tranexamic Acid in Brain Tumor Resections
NCT03722355PHASE3COMPLETEDHyperfractionated RT With BCNU Versus Conventional RT With BCNU for Supratentorial Malignant Glioma
NCT05345002PHASE2RECRUITINGAll-Trans Retinoic Acid (ATRA) Plus PD-1 Inhibition in Recurrent IDH-Mutant Glioma
NCT05683808PHASE2RECRUITINGVenous Thromboembolism Prevention in Outpatients With Glioma
NCT06161974PHASE2RECRUITINGStudy of Olutasidenib and Temozolomide in HGG
NCT07417761PHASE2RECRUITINGTuvusertib in Astrocytoma With ATRX Mutation
NCT07439172PHASE2NOT_YET_RECRUITINGPre-Radiation Chemotherapy for Newly Diagnosed High-Grade Glioma.
NCT00028158PHASE1/PHASE2COMPLETEDSafety and Effectiveness Study of G207, a Tumor-Killing Virus, in Patients With Recurrent Brain Cancer
NCT00165360PHASE2COMPLETEDProlonged Daily Temozolomide for Low-Grade Glioma
NCT00179803PHASE2COMPLETEDStem Cell Transplant for High Risk Central Nervous System (CNS) Tumors
NCT00360828PHASE2TERMINATEDPhase II Study of Irinotecan HCI for Recurrent Anaplastic Astrocytomas, Mixed Malignant Gliomas, and Oligodendrogliomas
NCT00389090PHASE2TERMINATEDA Phase II Study of Temozolomide and O6-Benzylguanine (O6-BG) in Patients With Temozolomide-Resistant Anaplastic Glioma
NCT00392171PHASE2COMPLETEDThe Effects of Continuous 28-day (28/28) Temozolomide Chemotherapy in Subjects With Recurrent Malignant Glioma Who Have Failed the Conventional 5-day (5/28) Treatment (P04601)
NCT00575887PHASE2COMPLETEDEfficacy of Protracted Temozolomide in Patients With Progressive High Grade Glioma
NCT00624728PHASE1/PHASE2COMPLETEDAssessment of 18FLT PET-CT for Volume Definition of High-grade Gliomas (GLIO-TEP)
NCT00683761PHASE1/PHASE2UNKNOWNA Study of 131I-TM601 in Adults With Recurrent Malignant Glioma
NCT00782626PHASE2COMPLETEDEverolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
NCT00783393PHASE2COMPLETEDSCH 52365 Phase II Clinical Study: A Study on the Efficacy and Safety of Monotherapy With SCH 52365 in Patients With First Relapsed Anaplastic Astrocytoma (Study P03745)
NCT00921167PHASE2COMPLETEDA Study to Evaluate the Efficacy of Bevacizumab Plus Irinotecan in Recurrent Gliomas
NCT01044966PHASE1/PHASE2TERMINATEDA Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma
NCT01125800PHASE1/PHASE2COMPLETEDA Phase I Dose Finding and Safety Study of Oral LDE225 in Children and a Phase II Portion to Assess Preliminary Efficacy in Recurrent or Refractory MB
NCT01288235PHASE2COMPLETEDProton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01351519PHASE2TERMINATEDA Study of Aminolevulinic Acid Used to Enhance Visualization and Surgical Removal of Brain Tumors
NCT02209428PHASE2UNKNOWNA Prospective Cohort to Study the Effect of Temozolomide on IDH Mutational Low Grade Gliomas
NCT02372409PHASE2TERMINATEDUsing MRI-Guided Laser Heat Ablation to Induce Disruption of the Peritumoral Blood Brain Barrier to Enhance Delivery and Efficacy of Treatment of Pediatric Brain Tumors
NCT02684058PHASE2COMPLETEDStudy of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Pediatric Patients With BRAF V600 Mutation Positive LGG or Relapsed or Refractory HGG Tumors
NCT02942264PHASE1/PHASE2TERMINATEDZotiraciclib (TG02) Plus Dose-Dense or Metronomic Temozolomide Followed by Randomized Phase II Trial of Zotiraciclib (TG02) Plus Temozolomide Versus Temozolomide Alone in Adults With Recurrent Anaplastic Astrocytoma and Glioblastoma
NCT03032484PHASE2COMPLETEDTVB- 2640 in Combination With Bevacizumab in Patients With First Relapse of High Grade Astrocytoma
NCT03649464PHASE1/PHASE2WITHDRAWNInvestigation of Oral OKN-007 in Recurrent High-grade Glioma Participants
NCT05297864PHASE2TERMINATEDPARP Inhibition for Gliomas (PI-4G or π4g)
NCT06439420PHASE2COMPLETEDCBT-I in Primary Brain Tumor Patients: Phase IIc Randomized Feasibility Pilot Trial
NCT03152318PHASE1ACTIVE_NOT_RECRUITINGA Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2
NCT03911388PHASE1RECRUITINGHSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
NCT05236036PHASE1ACTIVE_NOT_RECRUITINGMycophenolate Mofetil in Combination With Standard of Care for the Treatment of Glioblastoma
NCT05484622PHASE1ACTIVE_NOT_RECRUITINGStudy of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive IDH-1 Mutant Glioma

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
IMATINIB43
TEMOZOLOMIDE43
AMINOLEVULINIC ACID42
DABRAFENIB42
TRAMETINIB42
CARMUSTINE41
HYDROXYUREA41
MYCOPHENOLATE MOFETIL41
NIRAPARIB41
OLUTASIDENIB41
RETIFANLIMAB41
SONIDEGIB41
VORASIDENIB41
6-O-BENZYLGUANINE31
DISUFENTON SODIUM31
SEMUSTINE31
VELIPARIB31
CHLOROTOXIN21
DENIFANSTAT21
HILTONOL21
TUVUSERTIB21
ZOTIRACICLIB21
PF-0684000311
TROTABRESIB11
CHEMBL422879403
CHEMBL424819503
CHEMBL543395002
CHEMBL427884501

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 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot