Central nervous system cancer

disease

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Also known as cancer of central nervous systemcancer of CNScancer of the central nervous systemcancer of the CNScentral nervous system neoplasms, malignantcentral nervous system tumorcentral nervous system tumourcentral nervous system tumoursCNS cancerCNS malignant neoplasmsCNS neoplasmCNS neoplasms, malignantmalignant central nervous system neoplasmmalignant central nervous system tumormalignant central nervous system tumourmalignant CNS neoplasmmalignant CNS neoplasmsmalignant CNS tumormalignant CNS tumour

Summary

Central nervous system cancer (MONDO:0002714) is a cancer (an umbrella term covering 20 Mondo subtypes) with 29 cohort genes (114 GWAS associations across 19 studies; 11 CIViC-evidence somatic drivers) and 98 clinical trials. The dominant Reactome pathway is Oncogene Induced Senescence (4 cohort genes). Top therapeutic interventions include 2-mercaptoethanesulfonic acid, lomustine, and filgrastim.

At a glance

Classification: Cancer
Umbrella term: 20 Mondo subtypes
Cohort genes: 29
GWAS associations: 114
Clinical trials: 98

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	central nervous system cancer
Mondo ID	MONDO:0002714
EFO	EFO:0000326
MeSH	D016543
DOID	DOID:3620
NCIT	C4627
SNOMED CT	126951006
UMLS	C0348374
MedGen	87593
GARD	0027614
Anatomy (UBERON)	UBERON:0001017
Is cancer (heuristic)	yes

Also known as: cancer of central nervous system · cancer of CNS · cancer of the central nervous system · cancer of the CNS · central nervous system cancer · central nervous system neoplasms, malignant · central nervous system tumor · central nervous system tumour · central nervous system tumours · CNS cancer · CNS malignant neoplasms · CNS neoplasm · CNS neoplasms, malignant · malignant central nervous system neoplasm · malignant central nervous system tumor · malignant central nervous system tumour · malignant CNS neoplasm · malignant CNS neoplasms · malignant CNS tumor · malignant CNS tumour (+12 more)

Data availability: 114 GWAS associations (19 studies).

Disease family

An umbrella term covering 20 Mondo subtypes.

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

Related subtypes (5): sensory system cancer, ectomesenchymoma, adrenal gland neuroblastoma, cutaneous neuroendocrine carcinoma, peripheral nervous system cancer

Genetics & variants

GWAS landscape

114 GWAS associations across 19 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs55705857	7e-149	CCDC26	G	3.39
rs10069690	8e-74	TERT	T	1.61
rs2297440	4e-46	RTEL1-TNFRSF6B, RTEL1	C	1.48
rs634537	1e-45	CDKN2B-AS1	G	1.3
rs12803321	6e-43	PHLDB1	G	1.42
rs78378222	9e-38	TP53	G	2.53
rs75061358	5e-34	SEC61G-DT - EGFR	G	1.63
rs723527	5e-23	EGFR	A	1.25
rs4295627	5e-21	CCDC26	?	1.4
rs35850753	9e-20	TP53	T	2.53
rs6010620	5e-19	RTEL1-TNFRSF6B, RTEL1	G	1.56
rs8753	8e-18	POLR2A	T	3.09
rs2736100	2e-17	TERT	G	1.27
rs2157719	3e-17	CDKN2B-AS1	C	1.28
rs4977756	7e-15	CDKN2B-AS1	G	1.24
rs2853676	4e-14	TERT	A	1.26
rs77633900	2e-13	ETFA	C	1.35
rs140442570	3e-12	CUBNP2 - OR6D1P	?
rs369236100	4e-12	CCDST	C	2.28
rs648044	5e-12	ZBTB16	A	1.19
rs564536017	9e-12	SSU72L4 - SSU72L3	G	1.67
rs10852606	1e-11	HEATR3	C	1.18
rs577665147	1e-11	TENM2	G	3.79
rs373095162	2e-11	ZBTB7C	G	3.5
rs531528187	2e-11	ZIM2, PEG3	A	3.01
rs187076300	3e-11	LINC01343 - RNU6-753P	G	3.54
rs545299824	4e-11	STK10	G	3.39
rs567055062	4e-11	SVOPL	T	2.69
rs498872	5e-11	PHLDB1	?	1.22
rs10131032	5e-11	AKAP6	G	1.33

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST004347	Melin BS	2017	12,469	18,190	Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
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.
GCST004348	Melin BS	2017	5,819	18,190	Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.
GCST001058	Sanson M	2011	4,147	7,435	Chromosome 7p11.2 (EGFR) variation influences glioma risk.
GCST003227	Kinnersley B	2015	2,364	7,435	Genome-wide association study identifies multiple susceptibility loci for glioma.
GCST90477217	Verma A	2024	2,157	447,268	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST000439	Shete S	2009	1,878	3,670	Genome-wide association study identifies five susceptibility loci for glioma.
GCST003228	Kinnersley B	2015	1,783	7,435	Genome-wide association study identifies multiple susceptibility loci for glioma.
GCST002474	Walsh KM	2014	1,013	6,595	Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.
GCST011832	Foss-Skiftesvik J	2020	944	4,320	Genome-wide association study across pediatric central nervous system tumors implicates shared predisposition and points to 1q25.2 (PAPPA2) and 11p12 (LRRC4C) as novel candidate susceptibility loci.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	40
low_freq (0.01-0.05)	1
rare (<0.01)	8
unknown	1

Functional consequences

Consequence	Count
intron_variant	38
intergenic_variant	5
3_prime_UTR_variant	2
synonymous_variant	2
non_coding_transcript_exon_variant	1
regulatory_region_variant	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs55705857	8	129633446	A>G	0.057	intergenic_variant	CCDC26	7e-149	Tier 4: intronic/intergenic
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	1e-45	Tier 4: intronic/intergenic
rs12803321	11	118609400	G>A,C,T	0.357	intron_variant	PHLDB1	6e-43	Tier 4: intronic/intergenic
rs78378222	17	7668434	T>A,G	0.013	3_prime_UTR_variant	TP53	9e-38	Tier 2: splice/UTR
rs75061358	7	54848587	T>C,G	0.099	intron_variant	SEC61G-DT - EGFR	5e-34	Tier 4: intronic/intergenic
rs723527	7	55067179	A>C,G,T	0.427	intron_variant	EGFR	5e-23	Tier 4: intronic/intergenic
rs4295627	8	129673211	T>C,G	0.05	intergenic_variant	CCDC26	5e-21	Tier 4: intronic/intergenic
rs35850753	17	7675353	C>T	0.05	intron_variant	TP53	9e-20	Tier 4: intronic/intergenic
rs6010620	20	63678486	A>C,G,T	0.24	intron_variant	RTEL1-TNFRSF6B, RTEL1	5e-19	Tier 4: intronic/intergenic
rs8753	17	7514323	C>G,T	0.05	3_prime_UTR_variant	POLR2A	8e-18	Tier 2: splice/UTR
rs2736100	5	1286401	C>A,G,T	0.49	intron_variant	TERT	2e-17	Tier 4: intronic/intergenic
rs2157719	9	22033367	C>A,G,T	0.05	intron_variant	CDKN2B-AS1	3e-17	Tier 4: intronic/intergenic
rs4977756	9	22068653	G>A,C,T	0.4	intron_variant	CDKN2B-AS1	7e-15	Tier 4: intronic/intergenic
rs2853676	5	1288432	T>A,C,G	0.27	intron_variant	TERT	4e-14	Tier 4: intronic/intergenic
rs77633900	15	76246118	G>C	0.086	intron_variant	ETFA	2e-13	Tier 4: intronic/intergenic
rs140442570	10	45253087	A>C		intergenic_variant	CUBNP2 - OR6D1P	3e-12	Tier 4: intronic/intergenic
rs369236100	1	152243734	C>T	0.001	intron_variant	CCDST	4e-12	Tier 4: intronic/intergenic
rs648044	11	114160077	A>G,T	0.39	non_coding_transcript_exon_variant	ZBTB16	5e-12	Tier 4: intronic/intergenic
rs564536017	11	4298543	G>C,T	0.004	intergenic_variant	SSU72L4 - SSU72L3	9e-12	Tier 4: intronic/intergenic
rs10852606	16	50094961	T>A,C,G	0.287	intron_variant	HEATR3	1e-11	Tier 4: intronic/intergenic
rs577665147	5	167650047	G>A,C	0	intron_variant	TENM2	1e-11	Tier 4: intronic/intergenic
rs373095162	18	48200909	G>A,T	0	intron_variant	ZBTB7C	2e-11	Tier 4: intronic/intergenic
rs531528187	19	56823460	A>G	0	intron_variant	ZIM2, PEG3	2e-11	Tier 4: intronic/intergenic
rs187076300	1	38236458	G>A,T	0	intergenic_variant	LINC01343 - RNU6-753P	3e-11	Tier 4: intronic/intergenic
rs545299824	5	172155984	G>A,C	0	intron_variant	STK10	4e-11	Tier 4: intronic/intergenic
rs567055062	7	138686655	T>A,C	0	intron_variant	SVOPL	4e-11	Tier 4: intronic/intergenic
rs498872	11	118606652	A>C,G,T	0.05	regulatory_region_variant	PHLDB1	5e-11	Tier 3: regulatory
rs10131032	14	32780875	G>A	0.084	intron_variant	AKAP6	5e-11	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 65 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
CDKN2A	CDKN2A	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TERT	Act	PRCC	CIViC #79
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
ZBTB16	Act	ESCC,PRAD
PAPPA2			CIViC #14195
MAML2	ambiguous	AML,LUSC,VULVA
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
CDKN2B			CIViC #916
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
AKT3	Act	PROSTATE,SKCM	CIViC #7936
IDH1	Act	AML,CHOL,GB,GBM,HCC,HGGNOS,LGGNOS,MBL,MEL,MT,OS,PAST,PCM,PRAD,SKCM	CIViC #26
MDM4			CIViC #3466

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TERC	Orphanet:1775	Dyskeratosis congenita
TERC	Orphanet:2032	Idiopathic pulmonary fibrosis
TERC	Orphanet:88	Idiopathic aplastic anemia
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
ZBTB16	Orphanet:520	Acute promyelocytic leukemia
ZBTB16	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
LMF1	Orphanet:535453	Familial lipase maturation factor 1 deficiency
RTEL1	Orphanet:1775	Dyskeratosis congenita
RTEL1	Orphanet:2032	Idiopathic pulmonary fibrosis
RTEL1	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
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
CDKN2B	Orphanet:618	Familial melanoma
CDKN2B	Orphanet:652	Multiple endocrine neoplasia type 1
HEATR3	Orphanet:124	Diamond-Blackfan anemia
STN1	Orphanet:2032	Idiopathic pulmonary fibrosis

Cohort genes → proteins

29 cohort genes, 27 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	29

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gwas
ZBTB16	HGNC:12930	ENSG00000109906	Q05516	Zinc finger and BTB domain-containing protein 16	gwas
LMF1	HGNC:14154	ENSG00000103227	Q96S06	Lipase maturation factor 1	gwas
PAPPA2	HGNC:14615	ENSG00000116183	Q9BXP8	Pappalysin-2	gwas
RTEL1	HGNC:15888	ENSG00000258366	Q9NZ71	Regulator of telomere elongation helicase 1	gwas
MAML2	HGNC:16259	ENSG00000184384	Q8IZL2	Mastermind-like protein 2	gwas
SLC16A8	HGNC:16270	ENSG00000100156	O95907	Monocarboxylate transporter 3	gwas
LRIG1	HGNC:17360	ENSG00000144749	Q96JA1	Leucine-rich repeats and immunoglobulin-like domains protein 1	gwas
VTI1A	HGNC:17792	ENSG00000151532	Q96AJ9	Vesicle transport through interaction with t-SNAREs homolog 1A	gwas
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	gwas
CDKN2B	HGNC:1788	ENSG00000147883	P42772	Cyclin-dependent kinase 4 inhibitor B	gwas
PHLDB1	HGNC:23697	ENSG00000019144	Q86UU1	Pleckstrin homology-like domain family B member 1	gwas
RAVER2	HGNC:25577	ENSG00000162437	Q9HCJ3	Ribonucleoprotein PTB-binding 2	gwas
KANSL2	HGNC:26024	ENSG00000139620	Q9H9L4	KAT8 regulatory NSL complex subunit 2	gwas
HEATR3	HGNC:26087	ENSG00000155393	Q7Z4Q2	HEAT repeat-containing protein 3	gwas
STN1	HGNC:26200	ENSG00000107960	Q9H668	CST complex subunit STN1	gwas
CCDC26	HGNC:28416	ENSG00000229140		CCDC26 long non-coding RNA	gwas
LRRC4C	HGNC:29317	ENSG00000148948	Q9HCJ2	Leucine-rich repeat-containing protein 4C	gwas
POLR3B	HGNC:30348	ENSG00000013503	Q9NW08	DNA-directed RNA polymerase III subunit RPC2	gwas
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	gwas
ETFA	HGNC:3481	ENSG00000140374	P13804	Electron transfer flavoprotein subunit alpha, mitochondrial	gwas
AKAP6	HGNC:376	ENSG00000151320	Q13023	A-kinase anchor protein 6	gwas
AKT3	HGNC:393	ENSG00000117020	Q9Y243	RAC-gamma serine/threonine-protein kinase	gwas
IDH1	HGNC:5382	ENSG00000138413	O75874	Isocitrate dehydrogenase [NADP] cytoplasmic	gwas
KLF7	HGNC:6350	ENSG00000118263	O75840	Krueppel-like factor 7	gwas
MDM4	HGNC:6974	ENSG00000198625	O15151	Protein Mdm4	gwas
MPG	HGNC:7211	ENSG00000103152	P29372	DNA-3-methyladenine glycosylase	gwas

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.
ZBTB16	Zinc finger and BTB domain-containing protein 16	Acts as a transcriptional repressor.
LMF1	Lipase maturation factor 1	Involved in the maturation of specific proteins in the endoplasmic reticulum.
PAPPA2	Pappalysin-2	Metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the ‘163-Ser-\|-Lys-164’ bond.
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.
MAML2	Mastermind-like protein 2	Acts as a transcriptional coactivator for NOTCH proteins.
SLC16A8	Monocarboxylate transporter 3	Probable retinal pigment epithelium (RPE)-specific proton-coupled L-lactate transporter.
LRIG1	Leucine-rich repeats and immunoglobulin-like domains protein 1	Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation.
VTI1A	Vesicle transport through interaction with t-SNAREs homolog 1A	V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
CDKN2B	Cyclin-dependent kinase 4 inhibitor B	Interacts strongly with CDK4 and CDK6.
RAVER2	Ribonucleoprotein PTB-binding 2	May bind single-stranded nucleic acids.
KANSL2	KAT8 regulatory NSL complex subunit 2	Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at ‘Lys-5’- and ‘Lys-8’ (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiatio…
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).
STN1	CST complex subunit STN1	Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex.
LRRC4C	Leucine-rich repeat-containing protein 4C	May promote neurite outgrowth of developing thalamic neurons.
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.
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.
ETFA	Electron transfer flavoprotein subunit alpha, mitochondrial	Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase.
AKAP6	A-kinase anchor protein 6	Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the nuclear membrane or sarcoplasmic reticulum.
AKT3	RAC-gamma serine/threonine-protein kinase	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis.
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.
KLF7	Krueppel-like factor 7	Transcriptional factor.
MDM4	Protein Mdm4	Contributes to p53/TP53 regulation.
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.

Protein-family classification

Druggable: 8 · Difficult: 8 · Unknown: 13 · Druggable fraction: 0.28

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
Transporter	1	2.7×	0.501
Antibody/Immunoglobulin	2	2.0×	0.501
Kinase	2	1.9×	0.501
Scaffold/PPI	3	1.8×	0.501
Transcription factor	5	1.4×	0.501
Protease	1	1.3×	0.736
Enzyme (other)	2	0.8×	0.810
Other/Unknown	13	0.8×	0.916

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERC	Other/Unknown	no
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
ZBTB16	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
LMF1	Other/Unknown	no		LMF, LMF1/2_C, LMF1/2_N
PAPPA2	Protease	yes		Sushi_SCR_CCP_dom, Notch_dom, LamG-like
RTEL1	Other/Unknown	no		Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
MAML2	Other/Unknown	no		Mastermind-like_N, MAML1-3, MAML_N_sf
SLC16A8	Transporter	yes		MCT, MFS, MFS_dom
LRIG1	Antibody/Immunoglobulin	yes		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
VTI1A	Other/Unknown	no		T_SNARE_dom, Vesicle_trsprt_v-SNARE_N, SNARE
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
CDKN2B	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor
PHLDB1	Scaffold/PPI	no		FHA_dom, PH_domain, SMAD_FHA_dom_sf
RAVER2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RAVER2_RRM2
KANSL2	Transcription factor	no		Znf_KANL2-like, NSL2
HEATR3	Other/Unknown	no		ARM-like, ARM-type_fold, SYO1-like
STN1	Other/Unknown	no		NA-bd_OB_tRNA, NA-bd_OB-fold, Stn1
CCDC26	Other/Unknown	no
LRRC4C	Antibody/Immunoglobulin	yes		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
POLR3B	Other/Unknown	no		DNA-dir_RNAP_su2_dom, RNA_pol_bsu_CS, RNA_pol_Rpb2_7
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ETFA	Other/Unknown	no		ETF_a/FixB, Rossmann-like_a/b/a_fold, ETF_a/b_N
AKAP6	Other/Unknown	no		Spectrin_repeat, Spectrin/alpha-actinin
AKT3	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, PH_domain
IDH1	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom
KLF7	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
MDM4	Transcription factor	no		Znf_RING, Znf_RanBP2, SWIB_MDM2_domain
MPG	Enzyme (other)	yes	3.2.2.21	MPG, Formyl_transferase-like_C_sf, MPG_sf

Expression context

Cohort genes with no expression data: 0.

26 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)	29
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	4
jejunal mucosa	4
colonic epithelium	3
male germ line stem cell (sensu Vertebrata) in testis	3
secondary oocyte	3
cortical plate	3
bone marrow cell	2
ventricular zone	2
Brodmann (1909) area 23	2
calcaneal tendon	2
lower esophagus mucosa	2
gastrocnemius	2
buccal mucosa cell	2
nipple	2
oocyte	2
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
ganglionic eminence	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis
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
ZBTB16	281	broad	marker	skin of hip, Brodmann (1909) area 23, tibialis anterior
LMF1	276	ubiquitous	marker	right uterine tube, C1 segment of cervical spinal cord, sural nerve
PAPPA2	176	tissue_specific	marker	decidua, placenta, islet of Langerhans
RTEL1	134	ubiquitous	yes	sural nerve, right hemisphere of cerebellum, cerebellar hemisphere
MAML2	238	ubiquitous	marker	mucosa of paranasal sinus, cartilage tissue, mammary duct
SLC16A8	169	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, nucleus accumbens
LRIG1	290	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, ventricular zone
VTI1A	240	ubiquitous	marker	sural nerve, calcaneal tendon, pancreatic ductal cell
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
CDKN2B	219	ubiquitous	marker	jejunal mucosa, colonic mucosa, lower esophagus mucosa
PHLDB1	281	ubiquitous	marker	sural nerve, tibial nerve, middle frontal gyrus
RAVER2	236	ubiquitous	marker	jejunal mucosa, rectum, mucosa of transverse colon
KANSL2	134	ubiquitous	marker	skeletal muscle tissue, bone marrow, gastrocnemius
HEATR3	248	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
STN1	284	ubiquitous	marker	lower esophagus mucosa, oral cavity, esophagus mucosa
CCDC26	160	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium, bone marrow cell
LRRC4C	206	broad	marker	middle temporal gyrus, buccal mucosa cell, Brodmann (1909) area 23
POLR3B	247	ubiquitous	marker	secondary oocyte, esophagus squamous epithelium, endothelial cell
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ETFA	297	ubiquitous	marker	oocyte, secondary oocyte, jejunal mucosa
AKAP6	226	broad	marker	cortical plate, gastrocnemius, muscle of leg
AKT3	231	ubiquitous	marker	cortical plate, calcaneal tendon, embryo
IDH1	294	ubiquitous	marker	corpus epididymis, jejunal mucosa, adrenal tissue
KLF7	283	ubiquitous	marker	buccal mucosa cell, cortical plate, saphenous vein
MDM4	270	ubiquitous	marker	nipple, oocyte, colonic epithelium
MPG	280	ubiquitous	marker	ascending aorta, thoracic aorta, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 17.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
EGFR	18,421
CDKN2A	9,311
TERT	5,717
POLR3B	5,712
IDH1	5,464
ZBTB16	3,514
CDKN2B	3,431
MDM4	3,431
AKT3	3,392

Intra-cohort edges

A	B	Sources
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	MDM4	string_interaction
CDKN2A	PHLDB1	string_interaction
CDKN2A	TP53	string_interaction
CDKN2B	PHLDB1	string_interaction
CDKN2B	TP53	string_interaction
EGFR	HEATR3	intact
EGFR	LRIG1	biogrid_interaction, intact, string_interaction
EGFR	PHLDB1	string_interaction
IDH1	MDM4	string_interaction
IDH1	TP53	string_interaction
LRIG1	ZBTB16	biogrid_interaction
MDM4	TP53	biogrid_interaction, intact, string_interaction
MPG	TP53	intact
PHLDB1	RTEL1	string_interaction
PHLDB1	TERT	string_interaction
RTEL1	TERT	string_interaction

Structural data

PDB: 18 · AlphaFold-only: 9 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EGFR	P00533	388
TP53	P04637	313
IDH1	O75874	61
MDM4	O15151	39
POLR3B	Q9NW08	29
TERT	O14746	23
MPG	P29372	9
STN1	Q9H668	8
CDKN2A	P42771	5
ETFA	P13804	4
ZBTB16	Q05516	3
RTEL1	Q9NZ71	3
LRIG1	Q96JA1	2
AKT3	Q9Y243	2
PAPPA2	Q9BXP8	1
RAVER2	Q9HCJ3	1
KANSL2	Q9H9L4	1
LRRC4C	Q9HCJ2	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LMF1	Q96S06	90.49
CDKN2B	P42772	90.12
VTI1A	Q96AJ9	85.00
HEATR3	Q7Z4Q2	83.07
SLC16A8	O95907	77.38
PHLDB1	Q86UU1	60.40
KLF7	O75840	55.46
MAML2	Q8IZL2	46.21
AKAP6	Q13023	43.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 284. Enrichment computed across 29 evidence-associated genes (21 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 21 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Oncogene Induced Senescence	4	64.0×	9e-05	TP53, CDKN2A, CDKN2B, MDM4
Regulation of TP53 Degradation	4	55.8×	9e-05	TP53, CDKN2A, AKT3, MDM4
Cell Cycle	7	12.0×	9e-05	TERT, RTEL1, CDKN2A, CDKN2B, STN1, AKT3, MDM4
Stabilization of p53	3	108.8×	2e-04	TP53, CDKN2A, MDM4
Extension of Telomeres	3	85.9×	3e-04	TERT, RTEL1, STN1
Regulation of TP53 Expression and Degradation	3	74.2×	4e-04	CDKN2A, AKT3, MDM4
Telomere Maintenance	3	52.6×	9e-04	TERT, RTEL1, STN1
Oxidative Stress Induced Senescence	4	17.3×	0.003	TP53, CDKN2A, CDKN2B, MDM4
Gene expression (Transcription)	7	6.0×	0.003	MAML2, CDKN2A, CDKN2B, KANSL2, POLR3B, AKT3, MDM4
Chromosome Maintenance	3	30.2×	0.004	TERT, RTEL1, STN1
Mitotic G1 phase and G1/S transition	3	26.3×	0.005	CDKN2A, CDKN2B, AKT3
Regulation of TP53 Activity through Association with Co-factors	2	77.7×	0.007	TP53, AKT3
Regulation of beta-cell development	2	68.0×	0.007	MAML2, AKT3
p53-Dependent G1 DNA Damage Response	2	68.0×	0.007	CDKN2A, MDM4
p53-Dependent G1/S DNA damage checkpoint	2	68.0×	0.007	CDKN2A, MDM4
G1/S DNA Damage Checkpoints	2	64.0×	0.007	CDKN2A, MDM4
Cellular Senescence	3	19.7×	0.007	CDKN2A, CDKN2B, MDM4
Regulation of TP53 Activity	3	19.0×	0.008	CDKN2A, AKT3, MDM4
SUMOylation of transcription factors	2	54.4×	0.009	TP53, CDKN2A
Regulation of TP53 Activity through Methylation	2	51.8×	0.009	TP53, MDM4
MITF-M-regulated melanocyte development	3	16.3×	0.010	TERT, CDKN2A, AKT3
Telomere Extension By Telomerase	2	43.5×	0.012	TERT, RTEL1
Regulation of TP53 Activity through Acetylation	2	43.5×	0.012	TP53, AKT3
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	2	41.8×	0.012	EGFR, AKT3
G1 Phase	2	37.5×	0.014	CDKN2A, CDKN2B
Downregulation of ERBB2 signaling	2	36.2×	0.015	EGFR, AKT3
Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate	1	543.8×	0.016	IDH1
Evasion of Oncogene Induced Senescence Due to p14ARF Defects	1	543.8×	0.016	CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects	1	543.8×	0.016	CDKN2A
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	543.8×	0.016	TP53

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 26 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	3	114.4×	8e-04	TERT, TP53, CDKN2A
response to salt stress	2	144.0×	0.009	TP53, PAPPA2
cellular senescence	3	34.1×	0.009	TP53, CDKN2A, CDKN2B
positive regulation of miRNA transcription	3	33.5×	0.009	TERT, TP53, EGFR
telomere maintenance	3	30.9×	0.009	TERT, RTEL1, STN1
rRNA transcription	2	76.2×	0.017	TP53, CDKN2A
negative regulation of cell population proliferation	5	8.1×	0.017	TP53, ZBTB16, CDKN2A, CDKN2B, MDM4
DNA strand displacement	1	648.1×	0.023	RTEL1
RNA-templated transcription	1	648.1×	0.023	TERT
DNA strand elongation	1	648.1×	0.023	TERT
negative regulation of helicase activity	1	648.1×	0.023	TP53
regulation of phospholipid catabolic process	1	648.1×	0.023	IDH1
cellular response to actinomycin D	1	648.1×	0.023	TP53
siRNA transcription	1	648.1×	0.023	TERT
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	648.1×	0.023	TP53
negative regulation of G1 to G0 transition	1	648.1×	0.023	TP53
positive regulation of transdifferentiation	1	648.1×	0.023	TERT
negative regulation of telomere maintenance in response to DNA damage	1	648.1×	0.023	RTEL1
positive regulation of telomeric loop disassembly	1	648.1×	0.023	RTEL1
negative regulation of cardiocyte differentiation	1	648.1×	0.023	EGFR
negative regulation of telomere maintenance via telomerase	2	56.4×	0.023	TP53, STN1
negative regulation of cellular senescence	2	49.9×	0.023	TERT, AKT3
positive regulation of DNA replication	2	44.7×	0.023	STN1, EGFR
protein import into nucleus	3	16.6×	0.023	TERT, TP53, HEATR3
cellular response to hypoxia	3	14.0×	0.023	TERT, TP53, MDM4
positive regulation of G1/S transition of mitotic cell cycle	2	30.9×	0.027	TERT, EGFR
glyoxylate cycle	1	324.1×	0.029	IDH1
RNA-templated DNA biosynthetic process	1	324.1×	0.029	TERT
lactate transport	1	324.1×	0.029	SLC16A8
nuclear body organization	1	324.1×	0.029	CDKN2A

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Temozolomide	Approved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): ANTINEOPLASTON A10, Bevacizumab, Busulfan, Everolimus, Gemcitabine, Irinotecan, Nivolumab, Thiotepa.

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 7 · Undrugged: 22

Druggability breadth: 12 of 29 evidence-associated genes (41%) 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
AKT3	CAPIVASERTIB
IDH1	ENASIDENIB
MDM4	DIOSMIN
MPG	MITOXANTRONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
EGFR	175	4
AKT3	18	4
TERT	10	4
IDH1	10	4
MDM4	7	4
MPG	2	4
TERC	0	0
ZBTB16	0	0
LMF1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
NITROFURANTOIN	4	TP53
DIOSMIN	4	MDM4, TP53
VERTEPORFIN	4	MDM4, 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	TP53
FURAZOLIDONE	4	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	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): 4.

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
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
AKT3	660	Binding:644, Functional:16
IDH1	488	Binding:475, Functional:12, ADMET:1
TERT	391	Binding:389, Functional:2
MDM4	149	Binding:148, Functional:1
MPG	12	Binding:11, Functional:1
ZBTB16	3	Binding:3
SLC16A8	2	Binding:2
CDKN2A	2	Binding:2
PHLDB1	1	Binding:1
ETFA	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EGFR	2.7.10.1	receptor protein-tyrosine kinase
AKT3	2.7.11.1	non-specific serine/threonine protein kinase
IDH1	1.1.1.42	isocitrate dehydrogenase (NADP+)
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
AKT3	660
IDH1	488
MDM4	149

Pharmacogenomics

Cohort genes with a PharmGKB record: 29; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
NITROFURANTOIN	4	TP53
DIOSMIN	4	MDM4, TP53
VERTEPORFIN	4	MDM4, 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	TP53
FURAZOLIDONE	4	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	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)	7	TERT, TP53, EGFR, AKT3, IDH1, MDM4, MPG
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	PAPPA2, LRIG1, LRRC4C
D	Druggable family + AlphaFold only, no drug	1	SLC16A8
E	Difficult family or no structure, no drug	18	TERC, ZBTB16, LMF1, RTEL1, MAML2, VTI1A, CDKN2A, CDKN2B, PHLDB1, RAVER2 (+8 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LRIG1	0	EGFR
CDKN2B	0	TP53
PHLDB1	1	TERT
TERC	0	—
ZBTB16	3	—
LMF1	0	—
PAPPA2	0	—
RTEL1	0	—
MAML2	0	—
SLC16A8	2	—
VTI1A	0	—
CDKN2A	2	—
RAVER2	0	—
KANSL2	0	—
HEATR3	0	—
STN1	0	—
CCDC26	0	—
LRRC4C	0	—
POLR3B	0	—
ETFA	1	—
AKAP6	0	—
KLF7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 98.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	40
PHASE1	23
PHASE2	22
PHASE1/PHASE2	7
PHASE3	5
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00002875	PHASE3	COMPLETED	Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma
NCT00002944	PHASE3	COMPLETED	Combination Chemotherapy in Treating Children With Progressive Brain Tumors
NCT00078988	PHASE3	COMPLETED	High-Dose Chemotherapy Plus Autologous Stem Cell Transplantation Compared With Intermediate-Dose Chemotherapy Plus Autologous Stem Cell Transplantation With or Without Isotretinoin in Treating Young Patients With Recurrent High-Grade Gliomas
NCT00085098	PHASE3	COMPLETED	Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor
NCT00716976	PHASE3	COMPLETED	Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy
NCT02797366	PHASE2	RECRUITING	Proton Radiotherapy for Primary Central Nervous System Tumours in Adults
NCT02932280	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Dose Finding Study of Neratinib in Children and Young Adults With Cancer That Has Returned or Not Responded to Treatment
NCT04992013	PHASE2	ACTIVE_NOT_RECRUITING	Niraparib in Tumors Metastatic to the CNS
NCT05235074	PHASE1/PHASE2	RECRUITING	OH2 Oncolytic Viral Therapy in Central Nervous System Tumors
NCT07462507	PHASE2	RECRUITING	Inflammation in Primary and Secondary Malignancies of the Central Nervous System Using [C-11]-CS1P1
NCT07539441	PHASE1/PHASE2	RECRUITING	A Study of Mirdametinib in People With Central Nervous System Tumors
NCT00002594	PHASE2	COMPLETED	Combination Chemotherapy Followed by Bone Marrow and/or Peripheral Stem Cell Transplantation in Treating Patients With Recurrent Medulloblastoma or CNS Germ Cell Tumors
NCT00003203	PHASE2	COMPLETED	Carboplatin and Vincristine Plus Radiation Therapy Followed By Adjuvant Chemotherapy in Treating Young Patients With Newly Diagnosed CNS Embryonal Tumors
NCT00003573	PHASE2	COMPLETED	Etoposide Plus Radiation Therapy Followed by Combination Chemotherapy in Treating Children With Newly Diagnosed Advanced Medulloblastoma
NCT00005812	PHASE2	TERMINATED	Temozolomide in Treating Patients With Leptomeningeal Metastases From a Solid Tumor or Lymphoma
NCT00027846	PHASE2	COMPLETED	Observation or Radiation Therapy and/or Chemotherapy and Second Surgery in Treating Children Who Have Undergone Surgery for Ependymoma
NCT00031590	PHASE2	TERMINATED	Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma
NCT00047320	PHASE2	COMPLETED	Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors
NCT00066248	PHASE2	COMPLETED	Cyproheptadine and Megestrol in Preventing Weight Loss in Children With Cachexia Caused By Cancer or Cancer Treatment
NCT00107471	PHASE1/PHASE2	TERMINATED	Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma
NCT00187226	PHASE2	COMPLETED	A Study for Image-Guided Radiation Therapy in Pediatric Brain Tumors and Side Effects
NCT00238264	PHASE2	COMPLETED	Radiation Therapy in Treating Young Patients With Gliomas
NCT00400816	PHASE2	COMPLETED	Temozolomide in Treating Patients With Newly Diagnosed Anaplastic Oligodendroglioma or Mixed Oligoastrocytoma
NCT00407433	PHASE2	COMPLETED	Clinical Studies of Gemcitabine-Oxaliplatin
NCT00588523	PHASE2	COMPLETED	Intensive Chemotherapy and Autotransplantation for Patients With Newly Diagnosed Anaplastic Oligodendroglioma
NCT00588640	PHASE1/PHASE2	COMPLETED	Study of D-Methadone in Patients With Chronic Pain
NCT00589784	PHASE2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT01164189	PHASE2	COMPLETED	Bevacizumab in Recurrent Grade II and III Glioma
NCT01735747	PHASE2	UNKNOWN	Temozolomide, Nedaplatin, Vincristine, and Radiotherapy as First-line Treatment in Newly Diagnosed Primary CNS Lymphoma
NCT01985451	PHASE2	UNKNOWN	Pemetrexed and Temozolomide in Treating Patients With Relapsed Primary Central Nervous System Lymphoma （PCNSL）
NCT02496520	PHASE1/PHASE2	COMPLETED	Dendritic Cell-based Immunotherapy for Advanced Solid Tumours of Children and Young Adults
NCT03690869	PHASE1/PHASE2	TERMINATED	REGN2810 in Pediatric Patients With Relapsed, Refractory Solid, or Central Nervous System (CNS) Tumors and Safety and Efficacy of REGN2810 in Combination With Radiotherapy in Pediatric Patients With Newly Diagnosed or Recurrent Glioma
NCT04743310	PHASE2	COMPLETED	Fluorescence Detection of Adult Primary Central Nervous System Tumors With Tozuleristide and the Canvas System
NCT06322342	PHASE2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT03911388	PHASE1	RECRUITING	HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
NCT04185038	PHASE1	RECRUITING	Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors
NCT04732065	PHASE1	RECRUITING	ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors
NCT05081180	PHASE1	ACTIVE_NOT_RECRUITING	Study of Avelumab in Combination With Lenvatinib for Children With Primary CNS Tumors
NCT06104488	PHASE1	RECRUITING	A Study of Avutometinib for People With Solid Tumor Cancers
NCT00003141	PHASE1	COMPLETED	Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
2-MERCAPTOETHANESULFONIC ACID	4	4
LOMUSTINE	4	4
FILGRASTIM	4	3
PROCARBAZINE	4	3
THIOTEPA	4	3
VINCRISTINE	4	2
CARBOPLATIN	4	1
CEMIPLIMAB	4	1
CISPLATIN	4	1
CYPROHEPTADINE HYDROCHLORIDE	4	1
DURVALUMAB	4	1
FLUCICLOVINE F18	4	1
GALLIUM CITRATE GA 67	4	1
ISOTRETINOIN	4	1
MEGESTROL ACETATE	4	1
MEMANTINE HYDROCHLORIDE	4	1
NERATINIB	4	1
NIRAPARIB	4	1
SARGRAMOSTIM	4	1
SODIUM THIOSULFATE	4	1
SUNITINIB	4	1
THIOGUANINE	4	1
TILMANOCEPT	4	1
TOPOTECAN HYDROCHLORIDE	4	1
VINBLASTINE	4	1
METHIONINE	3	2
AVUTOMETINIB	3	1
ESMETHADONE	3	1
NEDAPLATIN	3	1
TOZULERISTIDE	2	2

Cohort genes: TERT, TP53, ZBTB16, PAPPA2, MAML2, CDKN2A, CDKN2B, EGFR, AKT3, IDH1, MDM4, TERC, LMF1, RTEL1, SLC16A8, LRIG1, VTI1A, PHLDB1, RAVER2, KANSL2, HEATR3, STN1, CCDC26, LRRC4C, POLR3B, ETFA, AKAP6, KLF7, MPG
Drugs: 2-MERCAPTOETHANESULFONIC ACID, Lomustine, Filgrastim, Procarbazine, Thiotepa, Vincristine, Carboplatin, Cemiplimab, Cisplatin, Cyproheptadine, Durvalumab, FLUCICLOVINE F18, GALLIUM CITRATE GA 67, Isotretinoin, Megestrol Acetate, Memantine, Neratinib, Niraparib, Sargramostim, Sodium Thiosulfate, Sunitinib, Thioguanine, Tilmanocept, Topotecan, Vinblastine, Methionine, Avutometinib, Esmethadone, Nedaplatin