Glioblastoma

Summary

Glioblastoma (MONDO:0018177) is a disease (an umbrella term covering 7 Mondo subtypes) with 42 cohort genes (1,099 GWAS associations across 6 studies) and 1,466 clinical trials. The dominant Reactome pathway is Constitutive Signaling by EGFRvIII (4 cohort genes). Molecularly, MGMT Promoter Methylation confers sensitivity to Temozolomide in Glioblastoma (CIViC Level A); 67 further subtype–drug associations are mapped below. Top therapeutic interventions include temozolomide, lomustine, and aminolevulinic acid.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 42
• GWAS associations: 1,099
• ClinVar variants: 10
• Phenotypes (HPO): 15
• Clinical trials: 1,466
• Precision-medicine evidence (CIViC): 68 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

7 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	3	Worldwide	Validated
Point prevalence	1-9 / 100 000	1	Worldwide	Validated
Annual incidence	1-9 / 100 000	2.52	Europe	Validated
Annual incidence	1-9 / 100 000	3.2	United States	Validated
Annual incidence	1-9 / 100 000	4.2	Croatia	Validated
Annual incidence	1-9 / 100 000	3.7	Greece	Validated
Annual incidence	1-9 / 100 000	3	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0012174	Glioblastoma multiforme	Obligate (100%)
HP:0025461	Abnormal cell morphology	Very frequent (80-99%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0012638	Abnormality of nervous system physiology	Frequent (30-79%)
HP:0000572	Visual loss	Frequent (30-79%)
HP:0000712	Emotional lability	Frequent (30-79%)
HP:0001273	Abnormal corpus callosum morphology	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0002181	Cerebral edema	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002463	Language impairment	Frequent (30-79%)
HP:0002500	Abnormal cerebral white matter morphology	Frequent (30-79%)
HP:0003470	Paralysis	Frequent (30-79%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	glioblastoma
Mondo ID	MONDO:0018177
EFO	EFO:0000519
MeSH	D005909
Orphanet	360
DOID	DOID:3068
NCIT	C3058
SNOMED CT	393563007
UMLS	C0017636
MedGen	42228
GARD	0002491
MedDRA	10018336, 10018337
NORD	1187
Is cancer (heuristic)	no

Also known as: GBM · GBM (glioblastoma) · giant cell glioblastoma (histologic variant) · glioblastoma · glioblastoma (disease) · glioblastoma multiforme · glioblastoma multiforme (disease) · gliosarcoma (histologic variant) · grade IV adult astrocytic tumor · grade IV adult astrocytic tumour · grade IV astrocytic neoplasm · grade IV astrocytic tumor · grade IV astrocytic tumour · grade IV astrocytoma · spongioblastoma multiforme · WHO grade IV glioma

Data availability: 10 ClinVar variants · 1,099 GWAS associations (6 studies) · 2 HPO phenotypes · 1,249 cell lines · 53 intOGen driver records.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › nervous system neoplasm › neuroepithelial neoplasm › glioma › astrocytic tumor › high grade astrocytic tumor › glioblastoma

Related subtypes (2): gliomatosis cerebri, anaplastic astrocytoma

Subtypes (7): classical glioblastoma, proneural glioblastoma, mesenchymal glioblastoma, neural glioblastoma, brain glioblastoma, adult glioblastoma, IDH-wildtype glioblastoma

Genetics & variants

GWAS landscape

1,099 GWAS associations across 6 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs10069690	8e-74	TERT	T	1.61
rs2297440	4e-46	RTEL1-TNFRSF6B, RTEL1	C	1.48
rs634537	7e-45	CDKN2B-AS1	G	1.37
rs75061358	5e-34	SEC61G-DT - EGFR	G	1.63
rs78378222	5e-29	TP53	G	2.63
rs72709458	6e-24	TERT	T	1.68
rs723527	5e-23	EGFR	A	1.25
rs6062302	1e-13	RTEL1, RTEL1-TNFRSF6B	C	1.43
rs35850753	4e-12	TP53	T	2.79
rs145929329	5e-12	CDKN2B-AS1	ATT	1.35
rs10852606	1e-11	HEATR3	C	1.18
rs55705857	9e-11	CCDC26	G	1.76
rs2235573	2e-10	SLC16A8	G	1.15
rs11979158	2e-10	EGFR	A	1.42
rs11233250	1e-09	MIR4300HG	C	1.24
rs12752552	2e-09	RAVER2	T	1.22
rs3851634	3e-09	POLR3B	T	1.23
rs72865837	3e-09	SPOPL-DT	?	5.73
rs61870246	3e-09	OSBPL5 - MRGPRG-AS1	?	10.31
rs59060240	4e-09	EGFR	T	1.41
rs141579660	5e-09	PIK3R1 - LINC02198	?	13.32
rs564284198	5e-09	CLTCL1	?	33.71
rs188173401	6e-09	RPL10P1 - NCSTNP1	?	21.73
rs572820010	1e-08	FBXO21	?	5.06
rs140314418	1e-08	LINC01808 - CISD1P1	?	20.55
rs2562152	2e-08	RHBDF1	T	1.21
rs182548820	2e-08	LINC02997 - RNU6-1232P	?	11.95
rs150388591	2e-08	DRAIC	?	5.01
rs115431060	2e-08	MAP3K20	?	21.35
rs118062537	2e-08	PCA3, PRUNE2	?	4.96

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004349	Melin BS	2017	6,191	18,190	Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
GCST003220	Kinnersley B	2015	1,783	7,435	Genome-wide association study identifies multiple susceptibility loci for glioma.
GCST006480	Ostrom QT	2018	1,533	10,582	Age-specific genome-wide association study in glioblastoma identifies increased proportion of ’lower grade glioma’-like features associated with younger age.
GCST001470	Xiao Y	2012	315	0	SSBP2 variants are associated with survival in glioblastoma patients.
GCST90296471	Foss-Skiftesvik J	2023	90	7,183	Multi-ancestry genome-wide association study of 4,069 children with glioma identifies 9p21.3 risk locus.
GCST90296481	Foss-Skiftesvik J	2023	90	7,183	Multi-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)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	2
Tier 3: regulatory	2
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	26
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	23

Functional consequences

Consequence	Count
intron_variant	31
intergenic_variant	13
synonymous_variant	2
regulatory_region_variant	2
3_prime_UTR_variant	1
splice_polypyrimidine_tract_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs10069690	5	1279675	C>T	0.276	intron_variant	TERT	8e-74	Tier 4: intronic/intergenic
rs2297440	20	63680946	T>C	0.204	intron_variant	RTEL1-TNFRSF6B, RTEL1	4e-46	Tier 4: intronic/intergenic
rs634537	9	22032153	T>G	0.411	intron_variant	CDKN2B-AS1	7e-45	Tier 4: intronic/intergenic
rs75061358	7	54848587	T>C,G	0.099	intron_variant	SEC61G-DT - EGFR	5e-34	Tier 4: intronic/intergenic
rs78378222	17	7668434	T>A,G	0.013	3_prime_UTR_variant	TP53	5e-29	Tier 2: splice/UTR
rs72709458	5	1283640	C>A,G,T	0.05	intron_variant	TERT	6e-24	Tier 4: intronic/intergenic
rs723527	7	55067179	A>C,G,T	0.427	intron_variant	EGFR	5e-23	Tier 4: intronic/intergenic
rs6062302	20	63689615	T>C	0.05	synonymous_variant	RTEL1, RTEL1-TNFRSF6B	1e-13	Tier 4: intronic/intergenic
rs35850753	17	7675353	C>T	0.05	intron_variant	TP53	4e-12	Tier 4: intronic/intergenic
rs145929329	9	22066213	ATTTT>A,AT,ATT,ATTT,ATTTTT,ATTTTTT,ATTTTTTTTTT	0.05	splice_polypyrimidine_tract_variant	CDKN2B-AS1	5e-12	Tier 2: splice/UTR
rs10852606	16	50094961	T>A,C,G	0.287	intron_variant	HEATR3	1e-11	Tier 4: intronic/intergenic
rs55705857	8	129633446	A>G	0.05	intergenic_variant	CCDC26	9e-11	Tier 4: intronic/intergenic
rs2235573	22	38081923	G>A	0.493	synonymous_variant	SLC16A8	2e-10	Tier 4: intronic/intergenic
rs11979158	7	55091656	A>G,T	0.05	intron_variant	EGFR	2e-10	Tier 4: intronic/intergenic
rs11233250	11	82685972	C>T	0.132	intron_variant	MIR4300HG	1e-09	Tier 4: intronic/intergenic
rs12752552	1	64763616	T>C	0.13	intron_variant	RAVER2	2e-09	Tier 4: intronic/intergenic
rs3851634	12	106419124	T>C	0.3	intron_variant	POLR3B	3e-09	Tier 4: intronic/intergenic
rs72865837	2	138077718	G>A,C,T	0.05	intergenic_variant	SPOPL-DT	3e-09	Tier 4: intronic/intergenic
rs61870246	11	3179212	C>T		intergenic_variant	OSBPL5 - MRGPRG-AS1	3e-09	Tier 4: intronic/intergenic
rs59060240	7	55080369	TAAA>T,TA,TAA,TAAAA,TAAAAA,TAAAAAAAAAAAA	0.05	intron_variant	EGFR	4e-09	Tier 4: intronic/intergenic
rs141579660	5	68338523	T>C,G		intergenic_variant	PIK3R1 - LINC02198	5e-09	Tier 4: intronic/intergenic
rs564284198	22	19211894	C>T		intron_variant	CLTCL1	5e-09	Tier 4: intronic/intergenic
rs188173401	21	27433299	T>C		intron_variant	RPL10P1 - NCSTNP1	6e-09	Tier 4: intronic/intergenic
rs572820010	12	117178907	A>AT	0.05	intron_variant	FBXO21	1e-08	Tier 4: intronic/intergenic
rs140314418	2	19800425	G>A		regulatory_region_variant	LINC01808 - CISD1P1	1e-08	Tier 3: regulatory
rs2562152	16	73898	A>C,T	0.15	intron_variant	RHBDF1	2e-08	Tier 4: intronic/intergenic
rs182548820	5	68129079	G>A,C		intergenic_variant	LINC02997 - RNU6-1232P	2e-08	Tier 4: intronic/intergenic
rs150388591	15	69682617	G>A	0.05	intron_variant	DRAIC	2e-08	Tier 4: intronic/intergenic
rs115431060	2	173126114	A>G,T		intron_variant	MAP3K20	2e-08	Tier 4: intronic/intergenic
rs118062537	9	76803211	T>C	0.05	intron_variant	PCA3, PRUNE2	2e-08	Tier 4: intronic/intergenic

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 pathogenic, 2 other, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
555284	NM_000051.4(ATM):c.8535G>A (p.Trp2845Ter)	ATM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
284290	NM_001123385.2(BCOR):c.3883_3884del (p.Leu1296fs)	BCOR	Pathogenic	criteria provided, multiple submitters, no conflicts
590849	NM_000251.3(MSH2):c.1958_1965del (p.Asn653fs)	MSH2	Pathogenic	criteria provided, single submitter
635110	NM_022552.5(DNMT3A):c.2710C>T (p.Pro904Ser)	DNMT3A	Likely pathogenic	no assertion criteria provided
1177131	inv(2)(p23.1p23.2)	ALK	Uncertain significance	no assertion criteria provided
1177132	inv(9)(p12q21.33)	CNTNAP3	Uncertain significance	no assertion criteria provided
1177145	t(10;19)(q26.13;q13.43)	FGFR2	Uncertain significance	no assertion criteria provided
438766	NM_002107.7(H3-3A):c.103G>A (p.Gly35Arg)	H3-3A	other	no assertion criteria provided
1177130	t(2;15)(q23.1;q25.3)	KIF5C	Uncertain significance	no assertion criteria provided
438772	NM_005120.3(MED12):c.5980C>T (p.Arg1994Trp)	MED12	other	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 203 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
TP53	TP53	GWAS, Orphanet
EGFR	EGFR	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma

Cohort genes → proteins

42 cohort genes, 41 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	10
civic_only	18
multi_evidence	14

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas,civic_evidence
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gwas,civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas,civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	gwas,civic_evidence
H3-3A	HGNC:4764	ENSG00000163041	P84243	Histone H3.3	clinvar,civic_evidence
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar,civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	civic_evidence
SOS1	HGNC:11187	ENSG00000115904	Q07889	Son of sevenless homolog 1	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence
H3C2	HGNC:4776	ENSG00000286522	P68431	Histone H3.1	civic_evidence
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	civic_evidence
IDH2	HGNC:5383	ENSG00000182054	P48735	Isocitrate dehydrogenase [NADP], mitochondrial	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
LRP1B	HGNC:6693	ENSG00000168702	Q9NZR2	Low-density lipoprotein receptor-related protein 1B	civic_evidence
MGMT	HGNC:7059	ENSG00000170430	P16455	Methylated-DNA–protein-cysteine methyltransferase	civic_evidence
ATRX	HGNC:886	ENSG00000085224	P46100	Transcriptional regulator ATRX	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
PIK3R1	HGNC:8979	ENSG00000145675	P27986	Phosphatidylinositol 3-kinase regulatory subunit alpha	civic_evidence
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	civic_evidence
POLE	HGNC:9177	ENSG00000177084	Q07864	DNA polymerase epsilon catalytic subunit A	civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	civic_evidence
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	civic_evidence
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	clinvar
CNTNAP3	HGNC:13834	ENSG00000106714	Q9BZ76	Contactin-associated protein-like 3	clinvar
LMF1	HGNC:14154	ENSG00000103227	Q96S06	Lipase maturation factor 1	gwas
SSBP2	HGNC:15831	ENSG00000145687	P81877	Single-stranded DNA-binding protein 2	gwas
RTEL1	HGNC:15888	ENSG00000258366	Q9NZ71	Regulator of telomere elongation helicase 1	gwas
SLC16A8	HGNC:16270	ENSG00000100156	O95907	Monocarboxylate transporter 3	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	clinvar
RAVER2	HGNC:25577	ENSG00000162437	Q9HCJ3	Ribonucleoprotein PTB-binding 2	gwas
HEATR3	HGNC:26087	ENSG00000155393	Q7Z4Q2	HEAT repeat-containing protein 3	gwas
CCDC26	HGNC:28416	ENSG00000229140		CCDC26 long non-coding RNA	gwas
DNMT3A	HGNC:2978	ENSG00000119772	Q9Y6K1	DNA (cytosine-5)-methyltransferase 3A	clinvar
POLR3B	HGNC:30348	ENSG00000013503	Q9NW08	DNA-directed RNA polymerase III subunit RPC2	gwas
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	clinvar
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	clinvar
KIF5C	HGNC:6325	ENSG00000168280	O60282	Kinesin heavy chain isoform 5C	clinvar
MPG	HGNC:7211	ENSG00000103152	P29372	DNA-3-methyladenine glycosylase	gwas
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
H3-3A	Histone H3.3	Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes.
ATM	Serine-protein kinase ATM	Serine/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.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
SOS1	Son of sevenless homolog 1	Promotes the exchange of Ras-bound GDP by GTP.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
H3C2	Histone H3.1	Core component of nucleosome.
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.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
LRP1B	Low-density lipoprotein receptor-related protein 1B	Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis.
MGMT	Methylated-DNA–protein-cysteine methyltransferase	Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA.
ATRX	Transcriptional regulator ATRX	Involved in transcriptional regulation and chromatin remodeling.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PIK3R1	Phosphatidylinositol 3-kinase regulatory subunit alpha	Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane.
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
POLE	DNA polymerase epsilon catalytic subunit A	Catalytic component of the DNA polymerase epsilon complex.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.
MED12	Mediator of RNA polymerase II transcription subunit 12	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
LMF1	Lipase maturation factor 1	Involved in the maturation of specific proteins in the endoplasmic reticulum.
RTEL1	Regulator of telomere elongation helicase 1	A probable ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability.
SLC16A8	Monocarboxylate transporter 3	Probable retinal pigment epithelium (RPE)-specific proton-coupled L-lactate transporter.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
BCOR	BCL-6 corepressor	Transcriptional corepressor.
RAVER2	Ribonucleoprotein PTB-binding 2	May bind single-stranded nucleic acids.
HEATR3	HEAT repeat-containing protein 3	Plays a role in ribosome biogenesis and in nuclear import of the 60S ribosomal protein L5/large ribosomal subunit protein uL18 (RPL5).
DNMT3A	DNA (cytosine-5)-methyltransferase 3A	Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development.
POLR3B	DNA-directed RNA polymerase III subunit RPC2	Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
KIF5C	Kinesin heavy chain isoform 5C	Microtubule-associated force-producing protein that may play a role in organelle transport.
MPG	DNA-3-methyladenine glycosylase	Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).

Protein-family classification

Druggable: 16 · Difficult: 7 · Unknown: 19 · Druggable fraction: 0.38

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
Kinase	8	5.3×	9e-04
Complement	1	6.4×	0.541
Scaffold/PPI	4	1.6×	0.541
Enzyme (other)	5	1.4×	0.541
Phosphatase	1	2.0×	0.559
Transporter	1	1.9×	0.559
Other/Unknown	19	0.8×	0.937
Transcription factor	3	0.6×	0.937

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
H3-3A	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, Histone-fold
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
SOS1	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
H3C2	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, Histone-fold
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
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
LRP1B	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
MGMT	Enzyme (other)	yes	2.1.1.63	MethylDNA_cys_MeTrfase_AS, MethylG_MeTrfase_N, MethylDNA_cys_MeTrfase_DNA-bd
ATRX	Transcription factor	no		SNF2_N, Helicase_C-like, Znf_FYVE_PHD
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PIK3R1	Kinase	yes	2.7.1.153	RhoGAP_dom, SH2, SH3_domain
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
POLE	Transcription factor	no	2.7.7.7	DNA-dir_DNA_pol_B_exonuc, DNA-dir_DNA_pol_B, RNaseH-like_sf
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
CNTNAP3	Other/Unknown	no		FA58C, EGF, Laminin_G
LMF1	Other/Unknown	no		LMF, LMF1/2_C, LMF1/2_N
SSBP2	Other/Unknown	no		LisH, SSDP_DNA-bd
RTEL1	Other/Unknown	no		Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
SLC16A8	Transporter	yes		MCT, MFS, MFS_dom
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD
RAVER2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RAVER2_RRM2
HEATR3	Other/Unknown	no		ARM-like, ARM-type_fold, SYO1-like
CCDC26	Other/Unknown	no
DNMT3A	Complement	yes	2.1.1.37	PWWP_dom, C5_MeTfrase, C5_DNA_meth_AS
POLR3B	Other/Unknown	no		DNA-dir_RNAP_su2_dom, RNA_pol_bsu_CS, RNA_pol_Rpb2_7
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
KIF5C	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
MPG	Enzyme (other)	yes	3.2.2.21	MPG, Formyl_transferase-like_C_sf, MPG_sf
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core

Expression context

Cohort genes with no expression data: 0.

40 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)	42
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	7
calcaneal tendon	7
ganglionic eminence	6
colonic epithelium	6
male germ line stem cell (sensu Vertebrata) in testis	6
secondary oocyte	4
jejunal mucosa	4
sural nerve	4
endothelial cell	4
adrenal tissue	3
cortical plate	3
tendon of biceps brachii	2
monocyte	2
corpus callosum	2
buccal mucosa cell	2
bone marrow cell	2
corpus epididymis	2
oocyte	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
H3-3A	134	ubiquitous	marker	ganglionic eminence, monocyte, ventricular zone
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
SOS1	289	ubiquitous	marker	colonic epithelium, jejunal mucosa, tendon of biceps brachii
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
H3C2	94	ubiquitous	marker	adrenal tissue, colonic epithelium, bone marrow cell
IDH1	294	ubiquitous	marker	corpus epididymis, jejunal mucosa, adrenal tissue
IDH2	292	ubiquitous	marker	apex of heart, gastrocnemius, hindlimb stylopod muscle
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
LRP1B	194	broad	marker	endothelial cell, Brodmann (1909) area 23, cortical plate
MGMT	261	ubiquitous	marker	right lobe of liver, liver, endometrium epithelium
ATRX	294	ubiquitous	marker	endothelial cell, calcaneal tendon, colonic epithelium
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PIK3R1	294	ubiquitous	marker	calcaneal tendon, caput epididymis, corpus epididymis
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
POLE	221	ubiquitous	marker	right hemisphere of cerebellum, right testis, cerebellar hemisphere
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
CNTNAP3	134		marker	male germ line stem cell (sensu Vertebrata) in testis, mucosa of stomach, lower esophagus muscularis layer
LMF1	276	ubiquitous	marker	right uterine tube, C1 segment of cervical spinal cord, sural nerve
SSBP2	293	ubiquitous	marker	cortical plate, ventricular zone, ganglionic eminence
RTEL1	134	ubiquitous	yes	sural nerve, right hemisphere of cerebellum, cerebellar hemisphere
SLC16A8	169	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, nucleus accumbens

Protein interactions among cohort

Intra-cohort edges: 63.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
PTEN	11,626
EZH2	9,646
CDKN2A	9,311
BRAF	7,394
ATM	7,383
KIT	6,087
ATRX	5,796
TERT	5,717

Intra-cohort edges

A	B	Sources
ALK	PIK3R1	intact
ATM	BRCA2	string_interaction
ATM	MSH2	string_interaction
ATM	TP53	biogrid_interaction, string_interaction
ATRX	BRCA2	string_interaction
ATRX	EZH2	intact
ATRX	H3-3A	intact
ATRX	IDH1	string_interaction
ATRX	MGMT	string_interaction
ATRX	TP53	string_interaction
BRAF	BRCA2	biogrid_interaction
BRAF	CDKN2A	string_interaction
BRAF	EGFR	biogrid_interaction
BRAF	FGFR2	biogrid_interaction
BRAF	PIK3CA	biogrid_interaction, string_interaction
BRAF	PMS2	string_interaction
BRAF	POLE	intact
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	SOS1	string_interaction
BRAF	TP53	string_interaction
BRCA2	MSH2	string_interaction
BRCA2	PMS2	string_interaction
BRCA2	TP53	string_interaction
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	MGMT	string_interaction
CDKN2A	RB1	string_interaction
CDKN2A	TP53	string_interaction
CDKN2B	TP53	string_interaction
DNMT3A	EZH2	intact, string_interaction
DNMT3A	H3-3A	intact
EGFR	HEATR3	intact
EGFR	IDH2	biogrid_interaction
EGFR	MGMT	string_interaction
EGFR	PIK3CA	string_interaction
EGFR	PIK3R1	string_interaction
EGFR	PTEN	string_interaction
EGFR	SOS1	intact, string_interaction
IDH1	IDH2	biogrid_interaction
IDH1	MGMT	string_interaction
IDH1	PTEN	string_interaction
IDH1	TP53	string_interaction
IDH2	MGMT	string_interaction
KIT	PIK3CA	biogrid_interaction
KIT	PIK3R1	biogrid_interaction, intact
KIT	TP53	biogrid_interaction
LRP1B	PIK3CA	string_interaction
LRP1B	TP53	string_interaction
MGMT	MPG	string_interaction
MGMT	PMS2	string_interaction
MGMT	TP53	string_interaction

Structural data

PDB: 33 · AlphaFold-only: 8 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
H3C2	P68431	548
EGFR	P00533	388
TP53	P04637	313
PIK3CA	P42336	135
BRAF	P15056	131
PIK3R1	P27986	105
H3-3A	P84243	103
SOS1	Q07889	91
ALK	Q9UM73	79
FGFR2	P21802	63
IDH1	O75874	61
KIT	P10721	52
DNMT3A	Q9Y6K1	43
EZH2	Q15910	38
MSH2	P43246	30
POLR3B	Q9NW08	29
TERT	O14746	23
MGMT	P16455	23
RB1	P06400	19
POLE	Q07864	18
ATM	Q13315	14
BRCA2	P51587	14
ATRX	P46100	12
PTEN	P60484	12
IDH2	P48735	11
PMS2	P54278	9
MPG	P29372	9
CDKN2A	P42771	5
BCOR	Q6W2J9	5
MED12	Q93074	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LMF1	Q96S06	90.49
CDKN2B	P42772	90.12
CNTNAP3	Q9BZ76	83.35
HEATR3	Q7Z4Q2	83.07
KIF5C	O60282	78.70
SLC16A8	O95907	77.38
SLTM	Q9NWH9	52.38
LRP1B	Q9NZR2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 542. Enrichment computed across 42 evidence-associated genes (34 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 34 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Constitutive Signaling by EGFRvIII	4	84.0×	4e-05	EGFR, SOS1, PIK3CA, PIK3R1
Signaling by ERBB2 ECD mutants	4	79.0×	4e-05	EGFR, SOS1, PIK3CA, PIK3R1
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	4	67.2×	6e-05	EGFR, SOS1, PIK3CA, PIK3R1
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	4	61.1×	6e-05	SOS1, KIT, PIK3CA, PIK3R1
Signaling by ERBB2 KD Mutants	4	49.8×	8e-05	EGFR, SOS1, PIK3CA, PIK3R1
DNA Repair	6	17.4×	8e-05	ATM, BRCA2, RTEL1, MGMT, MPG, MSH2
RAF/MAP kinase cascade	7	12.6×	8e-05	EGFR, BRAF, SOS1, FGFR2, KIT, PIK3CA, PIK3R1
Oxidative Stress Induced Senescence	6	16.0×	1e-04	TP53, CDKN2A, H3-3A, CDKN2B, EZH2, H3C2
Oncogene Induced Senescence	4	39.5×	2e-04	TP53, CDKN2A, CDKN2B, RB1
IRS-mediated signalling	3	91.6×	2e-04	SOS1, PIK3CA, PIK3R1
Signaling by FGFR4 in disease	3	84.0×	2e-04	SOS1, PIK3CA, PIK3R1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	3	77.5×	2e-04	SOS1, PIK3CA, PIK3R1
Signaling by PDGFRA extracellular domain mutants	3	77.5×	2e-04	SOS1, PIK3CA, PIK3R1
Signaling by LTK	3	77.5×	2e-04	SOS1, PIK3CA, PIK3R1
Constitutive Signaling by Aberrant PI3K in Cancer	5	18.7×	2e-04	EGFR, FGFR2, KIT, PIK3CA, PIK3R1
Signaling by FGFR2 in disease	4	31.2×	3e-04	SOS1, FGFR2, PIK3CA, PIK3R1
Stabilization of p53	3	67.2×	3e-04	TP53, CDKN2A, ATM
Signaling by FLT3 ITD and TKD mutants	3	67.2×	3e-04	SOS1, PIK3CA, PIK3R1
Signaling by SCF-KIT	4	29.2×	3e-04	SOS1, KIT, PIK3CA, PIK3R1
PI3K events in ERBB2 signaling	3	59.3×	4e-04	EGFR, PIK3CA, PIK3R1
GAB1 signalosome	3	56.0×	5e-04	EGFR, PIK3CA, PIK3R1
Resolution of D-Loop Structures	3	56.0×	5e-04	ATM, BRCA2, RTEL1
Tie2 Signaling	3	53.0×	5e-04	SOS1, PIK3CA, PIK3R1
Role of LAT2/NTAL/LAB on calcium mobilization	3	53.0×	5e-04	SOS1, PIK3CA, PIK3R1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	14.2×	5e-04	EGFR, FGFR2, KIT, PIK3CA, PIK3R1
Signaling by ALK	3	50.4×	5e-04	ALK, PIK3CA, PIK3R1
Diseases of DNA repair	3	50.4×	5e-04	ATM, BRCA2, MSH2
Signaling by FLT3 fusion proteins	3	50.4×	5e-04	SOS1, PIK3CA, PIK3R1
HDR through Homologous Recombination (HRR)	4	22.4×	5e-04	ATM, BRCA2, RTEL1, POLE
TP53 Regulates Transcription of DNA Repair Genes	4	21.3×	6e-04	TP53, ATM, MSH2, PMS2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 40 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
replicative senescence	4	99.1×	5e-05	TERT, TP53, CDKN2A, ATM
cellular senescence	5	37.0×	9e-05	TP53, CDKN2A, ATM, BRCA2, CDKN2B
negative regulation of glial cell proliferation	3	126.4×	4e-04	TP53, IDH2, RB1
subtelomeric heterochromatin formation	3	114.9×	4e-04	H3-3A, EZH2, ATRX
DNA damage response, signal transduction by p53 class mediator	4	35.9×	6e-04	TP53, ATM, BRCA2, ATRX
negative regulation of G1/S transition of mitotic cell cycle	4	35.9×	6e-04	CDKN2B, EZH2, PTEN, RB1
glyoxylate cycle	2	421.3×	6e-04	IDH1, IDH2
multicellular organism growth	5	17.1×	0.001	TP53, H3-3A, ATM, SOS1, ATRX
response to X-ray	3	66.5×	0.001	TP53, BRCA2, MSH2
epidermal growth factor receptor signaling pathway	4	24.8×	0.001	EGFR, BRAF, SOS1, PIK3CA
somatic stem cell population maintenance	4	24.8×	0.001	CDKN2A, BRAF, MED12, KIT
somatic recombination of immunoglobulin gene segments	2	210.7×	0.002	MSH2, PMS2
B cell differentiation	4	21.9×	0.002	EZH2, KIT, MSH2, PIK3R1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	4	21.1×	0.002	EGFR, PIK3CA, PIK3R1, PTEN
Ras protein signal transduction	4	20.6×	0.002	TP53, CDKN2A, SOS1, RB1
double-strand break repair	4	20.3×	0.002	TP53, ATM, BRCA2, MSH2
positive regulation of transcription by RNA polymerase II	11	4.1×	0.002	TP53, CDKN2A, EGFR, ATM, MED12, SSBP2, FGFR2, ATRX (+3 more)
isocitrate metabolic process	2	168.5×	0.002	IDH1, IDH2
negative regulation of mammary gland epithelial cell proliferation	2	168.5×	0.002	CDKN2A, BRCA2
digestive tract development	3	39.5×	0.002	FGFR2, KIT, RB1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	3	37.2×	0.003	TP53, BRCA2, MSH2
insulin-like growth factor receptor signaling pathway	3	37.2×	0.003	SOS1, PIK3CA, PIK3R1
positive regulation of isotype switching to IgA isotypes	2	140.4×	0.003	MSH2, PMS2
positive regulation of telomere maintenance via telomere lengthening	2	140.4×	0.003	ATM, RTEL1
embryonic organ development	3	36.1×	0.003	TP53, FGFR2, POLE
myeloid progenitor cell differentiation	2	120.4×	0.003	BRAF, KIT
autosome genomic imprinting	2	120.4×	0.003	DNMT3A, PIK3CA
determination of adult lifespan	3	32.4×	0.003	TP53, ATM, MSH2
heart development	5	9.8×	0.004	TERT, ATM, MED12, BCOR, PTEN
establishment of protein localization to telomere	2	105.3×	0.004	TERT, BRCA2

Therapeutics

Drugs indicated for this disease

3 approved, 21 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bevacizumab	Approved (phase 4)
Carmustine	Approved (phase 4)
Temozolomide	Approved (phase 4)
Carboplatin	Phase 3 (in late-stage trials)
Cediranib	Phase 3 (in late-stage trials)
Chloroquine	Phase 3 (in late-stage trials)
Cilengitide	Phase 3 (in late-stage trials)
Cintredekin Besudotox	Phase 3 (in late-stage trials)
Depatuxizumab Mafodotin	Phase 3 (in late-stage trials)
Dianhydrogalactitol	Phase 3 (in late-stage trials)
Edotecarin	Phase 3 (in late-stage trials)
Enzastaurin	Phase 3 (in late-stage trials)
Hydroxyurea	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Lomustine	Phase 3 (in late-stage trials)
Losartan	Phase 3 (in late-stage trials)
Marizomib	Phase 3 (in late-stage trials)
Nimotuzumab	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Ombipepimut-S	Phase 3 (in late-stage trials)
Rindopepimut	Phase 3 (in late-stage trials)
Semustine	Phase 3 (in late-stage trials)
Tofacitinib	Phase 3 (in late-stage trials)
Trabedersen	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): 6-O-BENZYLGUANINE, ANG1005, ANTINEOPLASTON A10, Abemaciclib, Aglatimagene Besadenovec, Aminolevulinic Acid, Ascorbic Acid, Aspirin, Asunercept, Atezolizumab, Atorvastatin, Avelumab, Axitinib, Azeliragon, Basiliximab, Bavituximab, Belinostat, Bortezomib, Bosutinib, Buparlisib, Cabazitaxel, Cabozantinib, Camrelizumab, Cannabidiol, Capecitabine, Carboxyamidotriazole, Carotuximab, Catequentinib, Celecoxib, Cemiplimab, Ceritinib, Cetuximab, Chlorpromazine, Cisplatin, Copper, Crenolanib, Dacomitinib Anhydrous, Dasatinib Anhydrous, Diphtheria Toxoid, Disulfiram, Dordaviprone, Dovitinib, Doxorubicin, Durvalumab, Erlotinib, Etirinotecan Pegol, Etoposide, Everolimus, Evofosfamide, Fenretinide, Ferumoxytol, Filgrastim, Fotemustine, Ganciclovir, Gefitinib, Hydroxychloroquine, Imatinib, Incomplete Freund’S Adjuvant, Infigratinib, Irinotecan, Isotretinoin, Keyhole Limpet Hemocyanin, Levetiracetam, Memantine, Metformin, Methimazole, Methionine, Neratinib, Nintedanib, Niraparib, Nogapendekin Alfa, Olaparib, Olaratumab, Onartuzumab, Onfekafusp Alfa, Osimertinib, Panobinostat, Pegargiminase, Pembrolizumab, Penpulimab, Pexidartinib, Phytonadione, Ponatinib, Procarbazine, Ramucirumab, Regorafenib, Regramostim, Retifanlimab, Romiplostim, Sacituzumab Govitecan, Sargramostim, Selinexor, Sintilimab, Sirolimus, Sodium Chloride, Sodium Dichloroacetate, Sorafenib, Streptozocin, Sunitinib, Talazoparib, Tamoxifen, Temsirolimus, Tesevatinib, Tetanus Toxoid Adsorbed, Thalidomide, Thioguanine, Tipifarnib, Tiragolumab, Tislelizumab, Tivozanib, Topotecan, Trebananib, Tremelimumab, Troriluzole, Ubidecarenone, Valacyclovir, Valproic Acid, Vandetanib, Vincristine, Vismodegib, Vitespen, Vorinostat.

Drug target analysis

Approved (phase 4): 16 · Phase ≥3: 17 · Phased (≥1): 19 · Undrugged: 23

Druggability breadth: 29 of 42 evidence-associated genes (69%) 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
TERT	BERBERINE
TP53	NITROFURANTOIN
EGFR	LEVODOPA
ATM	AMIODARONE HYDROCHLORIDE
BRAF	VEMURAFENIB
SOS1	IDARUBICIN
SLTM	CABOZANTINIB
EZH2	TAZEMETOSTAT
IDH1	ENASIDENIB
IDH2	ENASIDENIB
KIT	PONATINIB
PIK3CA	IDELALISIB
PIK3R1	IDELALISIB
FGFR2	PONATINIB
ALK	CERITINIB
MPG	MITOXANTRONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
KIT	99	4
PIK3CA	67	4
ALK	61	4
FGFR2	59	4
BRAF	48	4
ATM	35	4
PIK3R1	26	4
TERT	10	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	SOS1, TERT
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 16.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
ALK	1,815	Binding:1801, Functional:13, ADMET:1
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
FGFR2	966	Binding:940, Functional:22, ADMET:4
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
EZH2	839	Binding:833, Functional:6
PIK3R1	493	Binding:470, ADMET:23
IDH1	488	Binding:475, Functional:12, ADMET:1
SOS1	421	Binding:409, Functional:12
TERT	391	Binding:389, Functional:2
ATM	240	Binding:233, Functional:5, ADMET:2
DNMT3A	120	Binding:118, ADMET:1, Functional:1
MGMT	86	Binding:84, ADMET:2
IDH2	84	Binding:84
RB1	59	Binding:59
SLTM	14	Binding:14
MPG	12	Binding:11, Functional:1
MSH2	9	Binding:9
PTEN	8	Binding:8
H3-3A	6	Binding:6
MED12	6	Binding:6
KIF5C	3	Binding:3
CDKN2A	2	Binding:2
SLC16A8	2	Binding:2
BCOR	2	Binding:2
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ATM	2.7.11.1	non-specific serine/threonine protein kinase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)
IDH2	1.1.1.42	isocitrate dehydrogenase (NADP+)
KIT	2.7.10.1	receptor protein-tyrosine kinase
MGMT	2.1.1.63	methylated-DNA-[protein]-cysteine S-methyltransferase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PIK3R1	2.7.1.153	phosphatidylinositol-4,5-bisphosphate 3-kinase
POLE	2.7.7.7	DNA-directed DNA polymerase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
DNMT3A	2.1.1.37	DNA (cytosine-5-)-methyltransferase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase
ALK	2.7.10.1	receptor protein-tyrosine kinase
MPG	3.2.2.21	DNA-3-methyladenine glycosylase II

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TERT	391
TP53	869
EGFR	6,531
ATM	240
BRAF	1,442
SOS1	421
EZH2	839
IDH1	488
KIT	2,305
PIK3CA	2,034
PIK3R1	493
DNMT3A	120
FGFR2	966
ALK	1,815

Pharmacogenomics

Cohort genes with a PharmGKB record: 42; 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.

Compound	Max phase	Cohort target (bioactivity)
BERBERINE	4	TERT
DOXORUBICIN	4	SOS1, TERT
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	EGFR, TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	ATM, TP53
FURAZOLIDONE	4	ATM, TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	ATM, TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	16	TERT, TP53, EGFR, ATM, BRAF, SOS1, SLTM, EZH2, IDH1, IDH2 (+6 more)
B	Phased (≥1) drug, not yet approved	3	MGMT, RB1, MED12
C	Druggable family + PDB, no drug	2	PTEN, DNMT3A
D	Druggable family + AlphaFold only, no drug	1	SLC16A8
E	Difficult family or no structure, no drug	20	CDKN2A, H3-3A, BRCA2, H3C2, LRP1B, ATRX, PMS2, POLE, CNTNAP3, LMF1 (+10 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNMT3A	120	EZH2
PTEN	8	TP53
CDKN2B	0	TP53
CDKN2A	2	—
H3-3A	6	—
BRCA2	0	—
H3C2	0	—
LRP1B	0	—
ATRX	0	—
PMS2	1	—
POLE	0	—
CNTNAP3	0	—
LMF1	0	—
SSBP2	0	—
RTEL1	0	—
SLC16A8	2	—
BCOR	2	—
RAVER2	0	—
HEATR3	0	—
CCDC26	0	—
POLR3B	0	—
KIF5C	3	—
MSH2	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,466.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	406
PHASE1	347
PHASE1/PHASE2	180
EARLY_PHASE1	76
PHASE3	66
PHASE2/PHASE3	16
PHASE4	7
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT05342883	PHASE4	ACTIVE_NOT_RECRUITING	GammaTile and Stupp in Newly Diagnosed GBM
NCT07546669	PHASE4	NOT_YET_RECRUITING	Efficacy of Zoster Vaccination in Glioblastoma Patients
NCT00686725	PHASE4	COMPLETED	Standard Temodal (Temozolomide) Regimen Versus Standard Regimen Plus Early Postsurgery Temodal for Newly Diagnosed Glioblastoma Multiforme (Study P05572)
NCT01756729	PHASE4	TERMINATED	Post-approval Study of NovoTTF-100A in Recurrent GBM Patients
NCT05900908	PHASE4	WITHDRAWN	Post-operative Adjuvant Therapy w/wo GammaTile + Systemic Therapy
NCT06625047	PHASE4	COMPLETED	Comparing Telehealth and In-person Assessments in Glioma Patients Receiving Oral Chemotherapy
NCT02152982	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Temozolomide With or Without Veliparib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
NCT02685605	PHASE3	ACTIVE_NOT_RECRUITING	Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma Multiforme
NCT03663725	PHASE3	ACTIVE_NOT_RECRUITING	Treatment Intensification With Temozolomide in Adults With a Glioblastoma
NCT03970447	PHASE2/PHASE3	RECRUITING	A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
NCT04250922	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	LAM561 With RT and TMZ for Adults With Glioblastoma
NCT05095376	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma
NCT05100641	PHASE3	NOT_YET_RECRUITING	AV-GBM-1 vs Control as Adjunctive Therapy Following Surgery and RT/TMZ in Newly Diagnosed GBM
NCT05118776	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of ASC40 Tablets in Combination With Bevacizumab in Subjects With rGBM
NCT05271240	PHASE3	RECRUITING	Repeated Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab With Temozolomide and Radiation Compared to Temozolomide and Radiation Alone in Newly Diagnosed GBM
NCT05318612	PHASE3	ACTIVE_NOT_RECRUITING	Effectiveness of MR-guided LITT Therapy in Irresectable Glioblastoma (EMITT)
NCT05326464	PHASE3	ACTIVE_NOT_RECRUITING	Tofacitinib in Recurrent GBM Patients
NCT05439278	PHASE3	RECRUITING	Conventional Versus Hypofractionated Radiotherapy With Temozolomide in Elderly Glioblastoma
NCT05669820	PHASE2/PHASE3	RECRUITING	Antisecretory Factor Glioblastoma Phase 2
NCT05902169	PHASE3	RECRUITING	Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM
NCT06105619	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study of PLB1001 Enteric Capsules in the Treatment of sGBM/IDH Mutant Glioblastoma Patients With the ZM Fusion Gene (FUGEN).
NCT06388733	PHASE3	RECRUITING	A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma
NCT06448286	PHASE3	NOT_YET_RECRUITING	PH Weighted Chemical Exchange Saturation Transfer MRI-Based Surgical Resection to Improve Survival in Patients With Glioblastoma
NCT06477939	PHASE3	NOT_YET_RECRUITING	Study of Adding or Not Liposomal Transcrocetin (L-TC) With Concomitant HypoFractionated Radiation ThErapy and TEmozolomide in Newly Diagnosed GLioblastoma (GBM) Patients
NCT06496971	PHASE3	RECRUITING	A 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
NCT06556563	PHASE3	RECRUITING	EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
NCT06749925	PHASE3	NOT_YET_RECRUITING	Clinical Trial Assessing the Efficacy and Safety of Dendritic Cell-Based Immunotherapy for Glioblastoma
NCT07100730	PHASE3	RECRUITING	Study of TLX101-Tx Plus Standard of Care (SoC) Versus SoC Alone for the Treatment of Patients With Recurrent Glioblastoma
NCT07195591	PHASE3	RECRUITING	Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
NCT07461948	PHASE3	RECRUITING	Advanced Imaging Techniques for Evaluating the Tumor Immune Microenvironment in Glioblastoma Patients
NCT07605364	PHASE2/PHASE3	NOT_YET_RECRUITING	Testing the Addition of an Anti-Cancer Drug, Mycophenolate Mofetil, to the Usual Treatment (Radiation Therapy and Temozolomide) for Advanced Brain Cancer
NCT00045968	PHASE3	UNKNOWN	Study of a Drug [DCVax®-L] to Treat Newly Diagnosed GBM Brain Cancer
NCT00068952	PHASE3	COMPLETED	Study of IV Edotecarin Vs Temozolomide or Carmustine (BCNU) or Lomustine (CCNU) in Patients With Glioblastoma Multiforme
NCT00076986	PHASE3	COMPLETED	The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme
NCT00083447	PHASE3	WITHDRAWN	Study of Therapy With TransMID™ Compared to Best Standard of Care in Patients With Glioblastoma Multiforme
NCT00088400	PHASE3	COMPLETED	Comparison of TransMID vs Standard Treatment of Cancerous Brain Tumors
NCT00154375	PHASE3	COMPLETED	Study of Imatinib Mesylate in Combination With Hydroxyurea Versus Hydroxyurea Alone as an Oral Therapy in Patients With Temozolomide Resistant Progressive Glioblastoma
NCT00224978	PHASE3	COMPLETED	Chloroquine for Treatment of Glioblastoma Multiforme
NCT00295815	PHASE3	COMPLETED	Enzastaurin Versus Lomustine in Glioblastoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TEMOZOLOMIDE	4	39
LOMUSTINE	4	35
AMINOLEVULINIC ACID	4	8
DISULFIRAM	4	8
ATEZOLIZUMAB	4	6
CARMUSTINE	4	5
SUNITINIB	4	5
VANDETANIB	4	5
CHLOROQUINE	4	4
NIRAPARIB	4	4
RETIFANLIMAB	4	4
TRAMETINIB	4	4
ABEMACICLIB	4	3
COPPER	4	3
DABRAFENIB	4	3
FERUMOXYTOL	4	3
HYDROXYUREA	4	3
LONAFARNIB	4	3
NINTEDANIB	4	3
VALACYCLOVIR	4	3
VORINOSTAT	4	3
AXITINIB	4	2
CABOZANTINIB	4	2
CABOZANTINIB S-MALATE	4	2
CEMIPLIMAB	4	2
CERITINIB	4	2
CHLORPROMAZINE	4	2
CHLORPROMAZINE HYDROCHLORIDE	4	2
DACOMITINIB ANHYDROUS	4	2
ERLOTINIB HYDROCHLORIDE	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 68 predictive associations from 71 curated evidence items; also 18 prognostic, 17 diagnostic, 13 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
MGMT Promoter Methylation	Temozolomide	Sensitivity/Response	CIViC A	EID307
MGMT Promoter Methylation	Lomustine + Temozolomide	Sensitivity/Response	CIViC A	EID7303
IDH1 R132	Cetuximab	Sensitivity/Response	CIViC B	EID3718 +1
MGMT Underexpression	Temozolomide	Sensitivity/Response	CIViC B	EID2899 +1
DRD5 low expression	Dordaviprone	Sensitivity/Response	CIViC B	EID7600
EGFR Expression	Temozolomide + Nimotuzumab + 3-Dimensional Conformal Radiation Therapy	Sensitivity/Response	CIViC B	EID8299
EGFR Overexpression	Lomustine + Bevacizumab	Sensitivity/Response	CIViC B	EID10894
EGFR VIII	Erlotinib + Gefitinib	Sensitivity/Response	CIViC B	EID1128
EGFR VIII	Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor	Sensitivity/Response	CIViC B	EID772
EGFR VIII	Rindopepimut	Sensitivity/Response	CIViC B	EID971
EGFR::VSTM2A Fusion	Bevacizumab/Lomustine Regimen	Sensitivity/Response	CIViC B	EID11101
IDH1 R132S	Cetuximab	Sensitivity/Response	CIViC B	EID4033
KIT EXPRESSION	Sunitinib	Sensitivity/Response	CIViC B	EID10180
MGMT Promoter Methylation	Carmustine	Sensitivity/Response	CIViC B	EID308
MGMT RS16906252	Temozolomide	Sensitivity/Response	CIViC B	EID822
PIK3CA Mutation	Buparlisib	Sensitivity/Response	CIViC B	EID7072
PIK3R1 Mutation	Buparlisib	Sensitivity/Response	CIViC B	EID7073
PTEN Expression	Erlotinib + Gefitinib	Sensitivity/Response	CIViC B	EID1129
PTEN Expression	Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor	Sensitivity/Response	CIViC B	EID774
PTEN Mutation	Buparlisib	Sensitivity/Response	CIViC B	EID7074
SLC12A2 OVEREXPRESSION	Antisecretory Factor-enriched Egg Yolk Powder Supplement + Temozolomide	Sensitivity/Response	CIViC B	EID12689
VEGFA Overexpression	Bevacizumab	Sensitivity/Response	CIViC B	EID7013
PTEN Mutation	Nivolumab + Pembrolizumab	Resistance	CIViC B	EID8176
TP53 Mutation	Temozolomide	Resistance	CIViC B	EID7978
VEGFA Overexpression of VEGF121	Bevacizumab	Resistance	CIViC B	EID9490
ALK Expression	Crizotinib	Sensitivity/Response	CIViC C	EID7866
ARHGEF2::NTRK1 Fusion	Entrectinib	Sensitivity/Response	CIViC C	EID12606
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC C	EID3771
BRCA2 K3326*	Olaparib + Temozolomide	Sensitivity/Response	CIViC C	EID7724
EGFR Amplification AND EGFR EGFRVIII	Afatinib	Sensitivity/Response	CIViC C	EID773

+38 more predictive associations (showing top 30 by evidence level).