Osteoblastoma

Summary

Osteoblastoma (MONDO:0018936) is a disease with 2 cohort genes and 1 clinical trial. Top therapeutic interventions include denosumab.

At a glance

• Cohort genes: 2
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteoblastoma
Mondo ID	MONDO:0018936
MeSH	D018215
Orphanet	58040
DOID	DOID:0060098
ICD-11	1948326341
NCIT	C3294
UMLS	C0029417
MedGen	18212
GARD	0018854
MedDRA	10004430
Is cancer (heuristic)	no

Also known as: giant osteoid osteoma · ossifying giant cell tumor · ossifying giant cell tumour · osteoblastoma · osteoblastoma (disease) · osteoblastoma, benign

Data availability: 1 HPO phenotype · 1 cell line.

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 › osteoblastoma

Related subtypes (18): bone ameloblastoma, phalanx chondroma, ossifying fibroma, periosteal chondroma, chondroblastoma, osteoma, paranasal sinus Schneiderian papilloma, osteoid osteoma, CHILD syndrome, chondromyxoid fibroma, craniopharyngioma, 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: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOS	Orphanet:675396	Epithelioid hemangioma
FOSB	Orphanet:673556	Pseudomyogenic hemangioendothelioma
FOSB	Orphanet:675396	Epithelioid hemangioma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FOS	HGNC:3796	ENSG00000170345	P01100	Protein c-Fos	civic_evidence
FOSB	HGNC:3797	ENSG00000125740	P53539	Protein FosB	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOS	Protein c-Fos	Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor.
FOSB	Protein FosB	Heterodimerizes with proteins of the JUN family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to gene promoters containing an AP-1 consensus sequence 5’-TGA[GC]TCA-3’ and enhancing their transcr…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FOS	Other/Unknown	no		AP-1, bZIP, bZIP_sf
FOSB	Other/Unknown	no		AP-1, bZIP, bZIP_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gall bladder	2
mucosa of stomach	2
upper leg skin	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOS	294	ubiquitous	marker	mucosa of stomach, upper leg skin, gall bladder
FOSB	244	ubiquitous	marker	mucosa of stomach, upper leg skin, gall bladder

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FOS	8,853
FOSB	2,773

Intra-cohort edges

A	B	Sources
FOS	FOSB	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FOSB	P53539	12
FOS	P01100	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NGF-stimulated transcription	2	285.5×	1e-04	FOS, FOSB
Regulation of PD-L1(CD274) transcription	2	108.8×	5e-04	FOS, FOSB
Estrogen-dependent gene expression	2	75.6×	7e-04	FOS, FOSB
Activation of the AP-1 family of transcription factors	1	571.0×	0.005	FOS
NPAS4 regulates expression of target genes	1	248.3×	0.009	FOS
Estrogen-dependent nuclear events downstream of ESR-membrane signaling	1	219.6×	0.009	FOS
FCERI mediated MAPK activation	1	173.0×	0.010	FOS
TP53 Regulates Transcription of DNA Repair Genes	1	90.6×	0.017	FOS
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	73.2×	0.018	FOS
Interleukin-4 and Interleukin-13 signaling	1	51.4×	0.022	FOS
Senescence-Associated Secretory Phenotype (SASP)	1	49.6×	0.022	FOS
Oxidative Stress Induced Senescence	1	45.3×	0.022	FOS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to corticosterone	2	1123.5×	4e-05	FOS, FOSB
response to cAMP	2	510.7×	7e-05	FOS, FOSB
response to progesterone	2	495.6×	7e-05	FOS, FOSB
female pregnancy	2	210.7×	3e-04	FOS, FOSB
cellular response to calcium ion	2	200.6×	3e-04	FOS, FOSB
response to ethanol	2	146.5×	4e-04	FOS, FOSB
medium-term memory	1	8426.0×	7e-04	FOS
mononuclear cell differentiation	1	8426.0×	7e-04	FOS
cellular response to prolactin	1	8426.0×	7e-04	FOS
transcription by RNA polymerase II	2	70.5×	1e-03	FOS, FOSB
response to xenobiotic stimulus	2	69.1×	1e-03	FOS, FOSB
response to forskolin	1	4213.0×	0.001	FOS
conditioned taste aversion	1	2808.7×	0.001	FOS
skeletal muscle cell proliferation	1	1685.2×	0.002	FOS
response to gravity	1	1404.3×	0.002	FOS
cellular response to zinc ion starvation	1	1203.7×	0.003	FOS
myoblast proliferation	1	702.2×	0.004	FOS
cellular response to parathyroid hormone stimulus	1	702.2×	0.004	FOS
cellular response to phorbol 13-acetate 12-myristate	1	648.1×	0.004	FOS
response to morphine	1	601.9×	0.004	FOSB
neural retina development	1	468.1×	0.005	FOS
response to light stimulus	1	443.5×	0.005	FOS
behavioral response to cocaine	1	421.3×	0.005	FOSB
response to muscle stretch	1	383.0×	0.005	FOS
response to immobilization stress	1	366.4×	0.005	FOS
SMAD protein signal transduction	1	366.4×	0.005	FOS
integrated stress response signaling	1	351.1×	0.005	FOS
positive regulation of osteoclast differentiation	1	290.6×	0.006	FOS
response to amphetamine	1	247.8×	0.007	FOSB
response to nicotine	1	210.7×	0.008	FOSB

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
FOS	1	3
FOSB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CURCUMIN	3	FOS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FOS	11	Binding:10, Functional:1
FOSB	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
CURCUMIN	3	FOS

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	1	FOS
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FOSB

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)
FOSB	2	FOS

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