Low grade glioma

disease

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Also known as benign gliomaglioma, benignlow-grade glioma

Summary

Low grade glioma (MONDO:0021637) is a cancer (an umbrella term covering 6 Mondo subtypes) with 6 cohort genes (6 CIViC-evidence somatic drivers; 5 ClinVar predisposition records) and 69 clinical trials. The dominant Reactome pathway is Impaired BRCA2 binding to PALB2 (3 cohort genes). Molecularly, BRAF V600E confers sensitivity to Dabrafenib + Trametinib in Low Grade Glioma (CIViC Level A); 5 further subtype–drug associations are mapped below. Top therapeutic interventions include selumetinib, tovorafenib, and vinblastine.

At a glance

Classification: Cancer
Umbrella term: 6 Mondo subtypes
Cohort genes: 6
ClinVar variants: 5
Clinical trials: 69
Precision-medicine evidence (CIViC): 6 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	low grade glioma
Mondo ID	MONDO:0021637
DOID	DOID:0060101, DOID:0080829
NCIT	C132067
UMLS	C1997217
MedGen	744283
GARD	0025343
Is cancer (heuristic)	yes

Also known as: benign glioma · glioma, benign · low grade glioma · low-grade glioma

Data availability: 5 ClinVar variants.

Disease family

An umbrella term covering 6 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 › low grade glioma

Subtypes (6): schwannoma, angiocentric glioma, low grade astrocytic tumor, grade II glioma, childhood low-grade glioma, diffuse low-grade glioma, MAPK pathway–altered

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

5 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
37996	NM_000059.4(BRCA2):c.5782G>T (p.Glu1928Ter)	BRCA2	Pathogenic	reviewed by expert panel
945299	NM_007294.4(BRCA1):c.2407A>G (p.Ser803Gly)	BRCA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
51476	NM_000059.4(BRCA2):c.3499A>G (p.Ile1167Val)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
650794	NM_000059.4(BRCA2):c.442T>A (p.Cys148Ser)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410564	NM_002878.4(RAD51D):c.551A>T (p.Glu184Val)	RAD51D	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 52 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRAF	Act	BLCA,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,WDTC	CIViC #5
IDH1	Act	AML,CHOL,GB,GBM,HCC,HGGNOS,LGGNOS,MBL,MEL,MT,OS,PAST,PCM,PRAD,SKCM	CIViC #26
IDH2	Act	AML,BLCA,CHOL,LGGNOS,OS	CIViC #27
BRCA1	LoF	BLCA,BRCA,MEL,OVT	CIViC #6
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
RAD51D			CIViC #4765

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
IDH1	Orphanet:163634	Maffucci syndrome
IDH1	Orphanet:251576	Gliosarcoma
IDH1	Orphanet:251579	Giant cell glioblastoma
IDH1	Orphanet:296	Ollier disease
IDH1	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
IDH1	Orphanet:99646	Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria
IDH2	Orphanet:163634	Maffucci syndrome
IDH2	Orphanet:251589	Anaplastic astrocytoma
IDH2	Orphanet:251598	Protoplasmic astrocytoma
IDH2	Orphanet:251601	Fibrillary astrocytoma
IDH2	Orphanet:251604	Gemistocytic astrocytoma
IDH2	Orphanet:251627	Oligodendroglioma
IDH2	Orphanet:251630	Anaplastic oligodendroglioma
IDH2	Orphanet:251656	Oligoastrocytoma
IDH2	Orphanet:251663	Anaplastic oligoastrocytoma
IDH2	Orphanet:296	Ollier disease
IDH2	Orphanet:79315	D-2-hydroxyglutaric aciduria
IDH2	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	3
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	civic_evidence
IDH2	HGNC:5383	ENSG00000182054	P48735	Isocitrate dehydrogenase [NADP], mitochondrial	civic_evidence
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
RAD51D	HGNC:9823	ENSG00000185379	O75771	DNA repair protein RAD51 homolog 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
IDH1	Isocitrate dehydrogenase [NADP] cytoplasmic	Catalyzes 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.
IDH2	Isocitrate dehydrogenase [NADP], mitochondrial	Plays a role in intermediary metabolism and energy production.
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
RAD51D	DNA repair protein RAD51 homolog 4	Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	2	4.0×	0.333
Kinase	1	4.6×	0.396
Transcription factor	1	1.4×	0.719
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
IDH1	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
IDH2	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
RAD51D	Other/Unknown	no		AAA+_ATPase, Rad51_C, DNA_recomb/repair_RecA-like

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
ventricular zone	2
buccal mucosa cell	1
calcaneal tendon	1
colonic epithelium	1
adrenal tissue	1
corpus epididymis	1
jejunal mucosa	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1
primordial germ cell in gonad	1
secondary oocyte	1
male germ cell	1
oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
IDH1	294	ubiquitous	marker	corpus epididymis, jejunal mucosa, adrenal tissue
IDH2	292	ubiquitous	marker	apex of heart, gastrocnemius, hindlimb stylopod muscle
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
RAD51D	187	ubiquitous	yes	sperm, male germ cell, oocyte

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
BRAF	7,394
IDH1	5,464
IDH2	4,912
BRCA2	4,839
RAD51D	3,089

Intra-cohort edges

A	B	Sources
BRAF	BRCA2	biogrid_interaction
BRCA1	BRCA2	string_interaction
BRCA1	RAD51D	string_interaction
BRCA2	RAD51D	string_interaction
IDH1	IDH2	biogrid_interaction

Structural data

PDB: 6 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRAF	P15056	131
IDH1	O75874	61
BRCA1	P38398	33
RAD51D	O75771	17
BRCA2	P51587	14
IDH2	P48735	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 109. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 binding to PALB2	3	228.4×	6e-06	BRCA1, BRCA2, RAD51D
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	3	211.5×	6e-06	BRCA1, BRCA2, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	3	211.5×	6e-06	BRCA1, BRCA2, RAD51D
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	3	211.5×	6e-06	BRCA1, BRCA2, RAD51D
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	3	196.9×	6e-06	BRCA1, BRCA2, RAD51D
Homologous DNA Pairing and Strand Exchange	3	190.3×	6e-06	BRCA1, BRCA2, RAD51D
Resolution of D-loop Structures through Holliday Junction Intermediates	3	150.3×	1e-05	BRCA1, BRCA2, RAD51D
Presynaptic phase of homologous DNA pairing and strand exchange	3	135.9×	1e-05	BRCA1, BRCA2, RAD51D
HDR through Homologous Recombination (HRR)	3	95.2×	3e-05	BRCA1, BRCA2, RAD51D
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2	317.2×	2e-04	BRCA1, BRCA2
Diseases of DNA Double-Strand Break Repair	2	271.9×	2e-04	BRCA1, BRCA2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2	271.9×	2e-04	BRCA1, BRCA2
Resolution of D-Loop Structures	2	211.5×	3e-04	BRCA1, BRCA2
Diseases of DNA repair	2	190.3×	3e-04	BRCA1, BRCA2
Homology Directed Repair	2	102.9×	1e-03	BRCA1, BRCA2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2	102.9×	1e-03	BRCA1, BRCA2
Impaired BRCA2 binding to RAD51	2	102.9×	1e-03	BRCA1, BRCA2
Meiosis	2	95.2×	0.001	BRCA1, BRCA2
DNA Double-Strand Break Repair	2	82.8×	0.001	BRCA1, BRCA2
Reproduction	2	63.4×	0.002	BRCA1, BRCA2
TP53 Regulates Transcription of DNA Repair Genes	2	60.4×	0.002	BRCA1, RAD51D
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1	1903.3×	0.003	IDH1
Meiotic recombination	2	43.3×	0.004	BRCA1, BRCA2
NADPH regeneration	1	951.7×	0.004	IDH1
Defective DNA double strand break response due to BRCA1 loss of function	1	951.7×	0.004	BRCA1
Defective DNA double strand break response due to BARD1 loss of function	1	951.7×	0.004	BRCA1
Impaired BRCA2 translocation to the nucleus	1	634.4×	0.006	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	634.4×	0.006	BRCA2
NFE2L2 regulating TCA cycle genes	1	634.4×	0.006	IDH1
DNA Repair	2	32.8×	0.006	BRCA1, BRCA2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glyoxylate cycle	2	2808.7×	1e-05	IDH1, IDH2
isocitrate metabolic process	2	1123.5×	6e-05	IDH1, IDH2
telomere maintenance via recombination	2	510.7×	1e-04	BRCA2, RAD51D
NADP+ metabolic process	2	510.7×	1e-04	IDH1, IDH2
double-strand break repair via homologous recombination	3	78.0×	1e-04	BRCA1, BRCA2, RAD51D
regulation of DNA damage checkpoint	2	374.5×	2e-04	BRCA1, BRCA2
2-oxoglutarate metabolic process	2	312.1×	3e-04	IDH1, IDH2
female gonad development	2	267.5×	3e-04	BRCA2, IDH1
tricarboxylic acid cycle	2	170.2×	8e-04	IDH1, IDH2
cellular response to ionizing radiation	2	137.0×	0.001	BRCA1, BRCA2
regulation of phospholipid catabolic process	1	2808.7×	0.004	IDH1
double-strand break repair	2	67.7×	0.004	BRCA1, BRCA2
regulation of phospholipid biosynthetic process	1	1404.3×	0.005	IDH1
negative regulation of glial cell migration	1	1404.3×	0.005	IDH2
negative regulation of matrix metallopeptidase secretion	1	1404.3×	0.005	IDH2
mitotic recombination-dependent replication fork processing	1	1404.3×	0.005	BRCA2
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	936.2×	0.008	BRAF
DNA strand invasion	1	702.2×	0.010	RAD51D
NADPH regeneration	1	561.7×	0.010	IDH1
negative regulation of mammary gland epithelial cell proliferation	1	561.7×	0.010	BRCA2
positive regulation of axon regeneration	1	561.7×	0.010	BRAF
cellular response to indole-3-methanol	1	561.7×	0.010	BRCA1
negative regulation of synaptic vesicle exocytosis	1	561.7×	0.010	BRAF
chordate embryonic development	1	468.1×	0.011	BRCA1
CD4-positive, alpha-beta T cell differentiation	1	468.1×	0.011	BRAF
myeloid progenitor cell differentiation	1	401.2×	0.011	BRAF
NADP+ biosynthetic process	1	401.2×	0.011	IDH2
negative regulation of centriole replication	1	401.2×	0.011	BRCA1
positive regulation of D-glucose transmembrane transport	1	351.1×	0.011	BRAF
head morphogenesis	1	351.1×	0.011	BRAF

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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.

Symbol	Example approved molecule
BRAF	VEMURAFENIB
IDH1	ENASIDENIB
IDH2	ENASIDENIB
BRCA1	RIBOFLAVIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRAF	48	4
BRCA1	12	4
IDH1	10	4
IDH2	7	4
BRCA2	0	0
RAD51D	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
ENASIDENIB	4	IDH1, IDH2
IVOSIDENIB	4	IDH1, IDH2
VORASIDENIB	4	IDH1, IDH2
OLUTASIDENIB	4	IDH1, IDH2
ENASIDENIB MESYLATE	4	IDH2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
IDH1	488	Binding:475, Functional:12, ADMET:1
IDH2	84	Binding:84
BRCA1	13	Binding:9, Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)
IDH2	1.1.1.42	isocitrate dehydrogenase (NADP+)
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRAF	1,442
IDH1	488

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
ENASIDENIB	4	IDH1, IDH2
IVOSIDENIB	4	IDH1, IDH2
OLUTASIDENIB	4	IDH1, IDH2
ENASIDENIB MESYLATE	4	IDH2
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	BRAF, IDH1, IDH2, BRCA1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BRCA2, RAD51D

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	BRCA1
RAD51D	0	BRCA1

Clinical trials & evidence

Clinical trials

Clinical trials: 69.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	23
PHASE2	21
PHASE3	8
PHASE1	8
PHASE1/PHASE2	5
EARLY_PHASE1	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02455245	PHASE3	ACTIVE_NOT_RECRUITING	A Study Comparing Two Carboplatin Containing Regimens for Children and Young Adults With Previously Untreated Low Grade Glioma
NCT03871257	PHASE3	ACTIVE_NOT_RECRUITING	A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
NCT04166409	PHASE3	RECRUITING	A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
NCT04316039	PHASE2/PHASE3	RECRUITING	Radiotherapy Versus Radiotherapy Combined With Temozolomide in High-risk Low-grade Gliomas After Surgery
NCT04576117	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
NCT05566795	PHASE3	ACTIVE_NOT_RECRUITING	DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
NCT07004075	PHASE3	NOT_YET_RECRUITING	FCN-159 Monotherapy Versus Chemotherapy by Investigator’s Choice in Pediatric Low-grade Glioma Patients With BRAF Alteration
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT03763422	PHASE3	TERMINATED	Trial in Low Grade Glioma Patients: Wait or Treat
NCT01089101	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
NCT02358187	PHASE2	RECRUITING	A Vaccine Trial for Low Grade Gliomas
NCT02840409	PHASE2	ACTIVE_NOT_RECRUITING	Vinblastine +/- Bevacizumab in Children With Unresectable or Progressive Low Grade Glioma (LGG)
NCT03363217	PHASE2	ACTIVE_NOT_RECRUITING	Trametinib for Pediatric Neuro-oncology Patients With Refractory Tumor and Activation of the MAPK/ERK Pathway.
NCT03718767	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype
NCT04775485	PHASE2	RECRUITING	A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors
NCT04923126	PHASE1/PHASE2	RECRUITING	SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma
NCT05964569	PHASE2	RECRUITING	Feasibility of Individualized, Model-guided Optimization of Proton Beam Treatment Planning in Patients With Low Grade Glioma
NCT06132685	PHASE2	RECRUITING	Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial
NCT06159478	PHASE2	RECRUITING	Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)
NCT06684795	PHASE2	RECRUITING	FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery
NCT06712875	PHASE1/PHASE2	RECRUITING	MAPK Inhibition Combined With Anti-PD1 Therapy for BRAF-altered Pediatric Gliomas
NCT07110246	PHASE2	RECRUITING	Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
NCT00782626	PHASE2	COMPLETED	Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01497860	PHASE2	COMPLETED	Vinorelbine for Children With Progressive or Recurrent Low-grade Gliomas
NCT01837862	PHASE1/PHASE2	COMPLETED	A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas
NCT02023905	PHASE2	TERMINATED	Everolimus With and Without Temozolomide in Adult Low Grade Glioma
NCT02197637	PHASE2	COMPLETED	Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma
NCT02285439	PHASE1/PHASE2	COMPLETED	Study of MEK162 for Children With Low-Grade Gliomas
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03952598	PHASE2	SUSPENDED	Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy
NCT04044937	PHASE2	COMPLETED	Fluoroethyltyrosine for Evaluation of Intracranial Neoplasms
NCT04544007	PHASE2	TERMINATED	A Phase II Trial of Poly-ICLC for Low-Grade Gliomas
NCT04659421	PHASE2	COMPLETED	Study of Recombinant Human Endostatin Combined With CV Regimen in the Treatment of Pediatric Low-grade Gliomas
NCT03749187	PHASE1	ACTIVE_NOT_RECRUITING	BGB-290 and Temozolomide in Treating Isocitrate Dehydrogenase (IDH)1/2-Mutant Grade I-IV Gliomas
NCT05538130	PHASE1	RECRUITING	A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors
NCT06104488	PHASE1	RECRUITING	A Study of Avutometinib for People With Solid Tumor Cancers
NCT07441707	PHASE1	RECRUITING	A Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours
NCT00901849	PHASE1	COMPLETED	Tarceva/Rapamycin for Children With Low-grade Gliomas With or Without Neurofibromatosis Type 1 (NF1)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SELUMETINIB	4	7
TOVORAFENIB	4	6
VINBLASTINE	4	5
CARBOPLATIN	4	4
BINIMETINIB	4	2
DABRAFENIB	4	2
TEMOZOLOMIDE	4	2
MEBENDAZOLE	4	1
TAZEMETOSTAT	4	1
TRAMETINIB	4	1
VINCRISTINE	4	1
VORASIDENIB	4	1
AVUTOMETINIB	3	1
HILTONOL	2	1
LUVOMETINIB	2	1
MIRDAMETINIB	2	1
CLATURAFENIB	1	1
CHEMBL4228794	0	2
CHEMBL4248195	0	2
CHEMBL4788494	0	2
CHEMBL376464	0	1
CHEMBL4463209	0	1
CHEMBL5398431	0	1
CHEMBL5433950	0	1
CHEMBL4278845	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 6 predictive associations from 6 curated evidence items; also 1 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
BRAF V600E	Dabrafenib + Trametinib	Sensitivity/Response	CIViC A	EID12162
IDH1 R132C OR IDH1 R132H OR IDH1 R132L OR IDH1 R132G OR IDH1 R132S	Vorasidenib	Sensitivity/Response	CIViC A	EID11508
IDH2 R172K OR IDH2 R172G OR IDH2 R172W	Vorasidenib	Sensitivity/Response	CIViC A	EID11509
IDH2 R172M OR IDH2 R172S	Vorasidenib	Sensitivity/Response	CIViC A	EID12235
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC B	EID11770
GOPC::ROS1 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID11855

Cohort genes: BRAF, IDH1, IDH2, BRCA1, BRCA2, RAD51D
Drugs: Selumetinib, Tovorafenib, Vinblastine, Carboplatin, Binimetinib, Dabrafenib, Temozolomide, Mebendazole, Tazemetostat, Trametinib, Vincristine, Vorasidenib, Avutometinib, Vemurafenib, Entrectinib