Childhood spinal cord tumor

Summary

Childhood spinal cord tumor (MONDO:0002716) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 8 clinical trials. Top therapeutic interventions include bevacizumab, fludeoxyglucose f 18, and romidepsin.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood spinal cord tumor
Mondo ID	MONDO:0002716
DOID	DOID:3637
NCIT	C9234
UMLS	C1134515
MedGen	209512
Is cancer (heuristic)	yes

Also known as: childhood spinal cord neoplasm · paediatric spinal cord neoplasm · pediatric spinal cord neoplasm · spinal cord neoplasm of childhood

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › childhood neoplasm › childhood spinal cord tumor

Related subtypes (13): childhood astrocytic tumor, childhood kidney neoplasm, childhood infratentorial neoplasm, pediatric meningioma, childhood mediastinal neurogenic neoplasm, childhood ependymoma, childhood germ cell tumor, childhood optic nerve glioma, childhood malignant neoplasm, childhood carcinoid tumor, childhood choroid plexus neoplasm, childhood testicular neoplasm, childhood adrenal gland pheochromocytoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
H3-3A	Act	HGGNOS,PAST	CIViC #2537

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
H3-3A	HGNC:4764	ENSG00000163041	P84243	Histone H3.3	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
H3-3A	Histone H3.3	Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
H3-3A	Other/Unknown	no		Histone_H3/CENP-A, H2A/H2B/H3, Histone-fold

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
monocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
H3-3A	134	ubiquitous	marker	ganglionic eminence, monocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H3-3A	1,595

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
H3-3A	P84243	103

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Replacement of protamines by nucleosomes in the male pronucleus	1	271.9×	0.012	H3-3A
RNA Polymerase I Promoter Opening	1	184.2×	0.012	H3-3A
DNA methylation	1	178.4×	0.012	H3-3A
FXIIa activates plasma kallikrein-kinin system	1	173.0×	0.012	H3-3A
SIRT1 negatively regulates rRNA expression	1	170.4×	0.012	H3-3A
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	1	167.9×	0.012	H3-3A
Inhibition of DNA recombination at telomere	1	167.9×	0.012	H3-3A
Assembly of the ORC complex at the origin of replication	1	165.5×	0.012	H3-3A
Chromatin modifications during the maternal to zygotic transition (MZT)	1	163.1×	0.012	H3-3A
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex	1	163.1×	0.012	H3-3A
Condensation of Prophase Chromosomes	1	156.4×	0.012	H3-3A
Defective pyroptosis	1	156.4×	0.012	H3-3A
PRC2 methylates histones and DNA	1	152.3×	0.012	H3-3A
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	1	152.3×	0.012	H3-3A
CHD6, CHD7, CHD8, CHD9 subfamily	1	148.3×	0.012	H3-3A
Transcriptional regulation by small RNAs	1	144.6×	0.012	H3-3A
NuRD complex assembly	1	141.0×	0.012	H3-3A
Meiotic recombination	1	129.8×	0.012	H3-3A
Interaction of NuRD complexes with transcription factors	1	126.9×	0.012	H3-3A
Transcriptional regulation of granulopoiesis	1	125.5×	0.012	H3-3A
Pre-NOTCH Transcription and Translation	1	122.8×	0.012	H3-3A
B-WICH complex positively regulates rRNA expression	1	121.5×	0.012	H3-3A
RNA Polymerase I Promoter Escape	1	121.5×	0.012	H3-3A
Formation of the beta-catenin:TCF transactivating complex	1	120.2×	0.012	H3-3A
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.012	H3-3A
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.012	H3-3A
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.012	H3-3A
Regulation of PD-L1(CD274) transcription	1	108.8×	0.012	H3-3A
CHD1 and CHD2 subfamily	1	108.8×	0.012	H3-3A
Regulation of endogenous retroelements by KRAB-ZFP proteins	1	106.7×	0.012	H3-3A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of chromosome condensation	1	4213.0×	0.002	H3-3A
pericentric heterochromatin formation	1	3370.4×	0.002	H3-3A
subtelomeric heterochromatin formation	1	1532.0×	0.003	H3-3A
muscle cell differentiation	1	842.6×	0.004	H3-3A
telomere organization	1	624.1×	0.004	H3-3A
oocyte maturation	1	601.9×	0.004	H3-3A
nucleus organization	1	561.7×	0.004	H3-3A
embryo implantation	1	351.1×	0.006	H3-3A
single fertilization	1	183.2×	0.008	H3-3A
positive regulation of cell growth	1	183.2×	0.008	H3-3A
male gonad development	1	156.0×	0.008	H3-3A
spermatid development	1	145.3×	0.008	H3-3A
nucleosome assembly	1	140.4×	0.008	H3-3A
multicellular organism growth	1	137.0×	0.008	H3-3A
osteoblast differentiation	1	121.2×	0.009	H3-3A
cell population proliferation	1	102.8×	0.010	H3-3A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
H3-3A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
H3-3A	6	Binding:6

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	H3-3A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
H3-3A	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	6
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01236560	PHASE2/PHASE3	COMPLETED	Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma
NCT00381797	PHASE2	COMPLETED	Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma
NCT00053963	PHASE1	COMPLETED	FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia
NCT00326664	PHASE1	COMPLETED	AZD2171 in Treating Young Patients With Recurrent, Progressive, or Refractory Primary CNS Tumors
NCT00363272	PHASE1	COMPLETED	Ispinesib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Lymphoma
NCT00946335	PHASE1	COMPLETED	ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors
NCT01076530	PHASE1	COMPLETED	Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors
NCT01088763	PHASE1	TERMINATED	Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BEVACIZUMAB	4	2
FLUDEOXYGLUCOSE F 18	4	1
ROMIDEPSIN	4	1
TEMOZOLOMIDE	4	1
VORINOSTAT	4	1
VELIPARIB	3	2
CEDIRANIB MALEATE	3	1
ISPINESIB	2	1
CHEMBL4228794	0	1
CHEMBL4248195	0	1
CHEMBL4066465	0	1
CHEMBL2326523	0	1