Chondroblastoma

Summary

Chondroblastoma (MONDO:0004997) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include denosumab.

At a glance

• Cohort genes: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chondroblastoma
Mondo ID	MONDO:0004997
EFO	EFO:0000331
MeSH	D002804
DOID	DOID:2649
NCIT	C2945
UMLS	C0008441
MedGen	40270
GARD	0006047
Is cancer (heuristic)	no

Also known as: CHBL · chondroblastoma · chondroblastoma (disease)

Data availability: 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › musculoskeletal system benign neoplasm › benign connective and soft tissue neoplasm › bone benign neoplasm › chondroblastoma

Related subtypes (18): bone ameloblastoma, phalanx chondroma, ossifying fibroma, periosteal chondroma, osteoma, paranasal sinus Schneiderian papilloma, osteoid osteoma, CHILD syndrome, chondromyxoid fibroma, craniopharyngioma, osteoblastoma, benign neoplasm of pituitary gland, benign neoplasm of sphenoidal sinus, benign neoplasm of frontal sinus, benign neoplasm of maxillary sinus, benign neoplasm of ethmoidal sinus, benign neoplasm of lower jaw bone, desmoplastic fibroma

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

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
H3-3B	HGNC:4765	ENSG00000132475	P84243	Histone H3.3	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
H3-3B	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)
H3-3B	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
oocyte	1
secondary oocyte	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
H3-3B	308	ubiquitous	marker	oocyte, secondary oocyte, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
H3-3B	1,595

Structural data

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

Cohort genes with PDB structures (top 30)

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

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

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
H3-3B	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
H3-3B	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).

Chemical tractability of cohort targets

0 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.

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	H3-3B

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)
H3-3B	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03605199	PHASE2	UNKNOWN	Denosumab in Subjects With Giant Cell Rich Tumors of Bone

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DENOSUMAB	4	1