Idiopathic juvenile osteoporosis

Summary

Idiopathic juvenile osteoporosis (MONDO:0019409) is a disease caused by WNT1 (GenCC Strong), with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include alendronic acid.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: WNT1 (GenCC Strong)
• Cohort genes: 1
• Phenotypes (HPO): 6
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

6 HPO clinical features (Orphanet curated; top 6 by frequency):

HPO ID	Term	Frequency
HP:0000939	Osteoporosis	Very frequent (80-99%)
HP:0002653	Bone pain	Very frequent (80-99%)
HP:0002757	Recurrent fractures	Very frequent (80-99%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0002953	Vertebral compression fracture	Frequent (30-79%)
HP:0002808	Kyphosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic juvenile osteoporosis
Mondo ID	MONDO:0019409
MeSH	C537700
OMIM	259750
Orphanet	85193
DOID	DOID:12559
ICD-11	183642011
NCIT	C119996
SNOMED CT	3345002
UMLS	C0264080
MedGen	120494
GARD	0006760
Is cancer (heuristic)	no

Also known as: idiopathic juvenile osteoporosis · IJO · Ijo · juvenile osteoporosis · Paediatric osteoporosis · Pediatric osteoporosis

Data availability: 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone remodeling disease › bone resorption disease › osteoporosis › idiopathic juvenile osteoporosis

Related subtypes (6): nephrolithiasis/osteoporosis, hypophosphatemic, postmenopausal osteoporosis, X-linked osteoporosis with fractures, drug-induced osteoporosis, pregnancy associated osteoporosis, premenopausal osteoporosis

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: 8 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
WNT1	Strong	Autosomal dominant	idiopathic juvenile osteoporosis	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT1	Orphanet:216812	Osteogenesis imperfecta type 3
WNT1	Orphanet:216820	Osteogenesis imperfecta type 4
WNT1	Orphanet:85193	Idiopathic juvenile osteoporosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WNT1	HGNC:12774	ENSG00000125084	P04628	Proto-oncogene Wnt-1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT1	Proto-oncogene Wnt-1	Ligand for members of the frizzled family of seven transmembrane receptors.

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)
WNT1	Other/Unknown	no		Wnt, Wnt1, Wnt_CS

Expression context

Cohort genes with no expression data: 0.

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
granulocyte	1
nucleus accumbens	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT1	73	tissue_specific	yes	granulocyte, nucleus accumbens, superior frontal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WNT1	2,506

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT1	P04628	86.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
WNT ligand biogenesis and trafficking	1	423.0×	0.007	WNT1
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.007	WNT1
PCP/CE pathway	1	300.5×	0.007	WNT1
Class B/2 (Secretin family receptors)	1	190.3×	0.008	WNT1
Transcriptional regulation of white adipocyte differentiation	1	129.8×	0.008	WNT1
TCF dependent signaling in response to WNT	1	117.7×	0.008	WNT1

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
cerebellum formation	1	16852.0×	0.001	WNT1
midbrain-hindbrain boundary maturation during brain development	1	16852.0×	0.001	WNT1
diencephalon development	1	8426.0×	0.001	WNT1
central nervous system morphogenesis	1	8426.0×	0.001	WNT1
astrocyte-dopaminergic neuron signaling	1	5617.3×	0.001	WNT1
Spemann organizer formation	1	5617.3×	0.001	WNT1
positive regulation of dermatome development	1	5617.3×	0.001	WNT1
forebrain anterior/posterior pattern specification	1	4213.0×	0.001	WNT1
cell proliferation in midbrain	1	3370.4×	0.002	WNT1
embryonic axis specification	1	2407.4×	0.002	WNT1
neuron fate determination	1	2106.5×	0.002	WNT1
positive regulation of hematopoietic stem cell proliferation	1	1872.4×	0.002	WNT1
spinal cord association neuron differentiation	1	1296.3×	0.002	WNT1
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	1	1296.3×	0.002	WNT1
positive regulation of insulin-like growth factor receptor signaling pathway	1	1203.7×	0.002	WNT1
hepatocyte differentiation	1	1203.7×	0.002	WNT1
midbrain dopaminergic neuron differentiation	1	1203.7×	0.002	WNT1
negative regulation of cell-substrate adhesion	1	1053.2×	0.003	WNT1
negative regulation of cell-cell adhesion	1	991.3×	0.003	WNT1
cellular response to peptide hormone stimulus	1	842.6×	0.003	WNT1
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.003	WNT1
signal transduction in response to DNA damage	1	802.5×	0.003	WNT1
embryonic brain development	1	802.5×	0.003	WNT1
hematopoietic stem cell proliferation	1	648.1×	0.003	WNT1
negative regulation of cellular senescence	1	648.1×	0.003	WNT1
myoblast fusion	1	601.9×	0.003	WNT1
positive regulation of lamellipodium assembly	1	601.9×	0.003	WNT1
midbrain development	1	601.9×	0.003	WNT1
animal organ regeneration	1	601.9×	0.003	WNT1
T cell differentiation in thymus	1	411.0×	0.004	WNT1

Therapeutics

Drug target analysis

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

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
WNT1	1	1

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CIRTUVIVINT	1	WNT1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
WNT1	10	Binding:10

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

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)
CIRTUVIVINT	1	WNT1

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	WNT1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00920075	Not specified	COMPLETED	Alendronate in Juvenile Osteoporosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALENDRONIC ACID	4	1