Juvenile nasopharyngeal angiofibroma

Summary

Juvenile nasopharyngeal angiofibroma (MONDO:0017340) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include sirolimus.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 8
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.6666	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

8 HPO clinical features (Orphanet curated; top 8 by frequency):

HPO ID	Term	Frequency
HP:0030429	Juvenile nasopharyngeal angiofibroma	Obligate (100%)
HP:0000282	Facial edema	Frequent (30-79%)
HP:0000421	Epistaxis	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0000651	Diplopia	Frequent (30-79%)
HP:0001742	Nasal congestion	Frequent (30-79%)
HP:0002516	Increased intracranial pressure	Occasional (5-29%)
HP:0012198	Juvenile colonic polyposis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile nasopharyngeal angiofibroma
Mondo ID	MONDO:0017340
Orphanet	289596
NCIT	C27479
SNOMED CT	716590006
UMLS	C1367536
MedGen	237137
GARD	0021144
Is cancer (heuristic)	no

Also known as: JNA · juvenile nasopharyngeal angiofibroma · juvenile nasopharyngeal angiofibroma (disease) · nasopharyngeal angiofibroma · nasopharyngeal juvenile angiofibroma

Data availability: 2 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › head and neck neoplasm › juvenile nasopharyngeal angiofibroma

Related subtypes (36): cranial nerve neoplasm, cavernous hemangioma of face, gasserian ganglion meningioma, nasal cavity neoplasm, palatal neoplasm, nasopharyngeal neoplasm, head and neck cancer, head and neck paraganglioma, nasal cavity and paranasal sinus lethal midline granuloma, familial thyroglossal duct cyst, laryngeal neuroendocrine neoplasm, laryngotracheal angioma, facial dermoid cyst, epignathus, nasal glial heterotopia, nasal ganglioglioma, malignant epithelial tumor of salivary glands, benign epithelial tumor of salivary glands, recurrent respiratory papillomatosis, ocular adnexal lymphoma, gingival neoplasm, odontogenic neoplasm, eye neoplasm, ear neoplasm, tongue neoplasm, buccal mucosa neoplasm, lip neoplasm, tonsil neoplasm, neoplasm of neck, tumor of salivary gland, neoplasm of hypopharynx, neoplasm of oropharynx, neoplasm of floor of mouth, lipoma of face, skull neoplasm, nasal cavity and paranasal sinus neoplasm

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

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
376228	NM_001904.4(CTNNB1):c.94G>A (p.Asp32Asn)	CTNNB1	Pathogenic	criteria provided, single submitter
3340441	NM_001904.4(CTNNB1):c.88_111del (p.Tyr30_Ser37del)	CTNNB1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNNB1	Orphanet:1501	Adrenocortical carcinoma
CTNNB1	Orphanet:210159	Adult hepatocellular carcinoma
CTNNB1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
CTNNB1	Orphanet:33402	Pediatric hepatocellular carcinoma
CTNNB1	Orphanet:404473	Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1	Orphanet:54595	Craniopharyngioma
CTNNB1	Orphanet:569248	Microcystic stromal tumor
CTNNB1	Orphanet:689430	Adenoid ameloblastoma
CTNNB1	Orphanet:873	Desmoid tumor
CTNNB1	Orphanet:891	Familial exudative vitreoretinopathy
CTNNB1	Orphanet:91414	Pilomatrixoma
CTNNB1	Orphanet:952	Acrofacial dysostosis, Weyers type

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
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.

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)
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin

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
adrenal tissue	1
periodontal ligament	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNB1	15,668

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNB1	P35222	50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 46. 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
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	2284.0×	0.004	CTNNB1
CDH11 homotypic and heterotypic interactions	1	1631.4×	0.004	CTNNB1
Regulation of CDH19 Expression and Function	1	1427.5×	0.004	CTNNB1
InlA-mediated entry of Listeria monocytogenes into host cells	1	1268.9×	0.004	CTNNB1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	1142.0×	0.004	CTNNB1
RUNX3 regulates WNT signaling	1	1142.0×	0.004	CTNNB1
Apoptotic cleavage of cell adhesion proteins	1	1038.2×	0.004	CTNNB1
Regulation of CDH11 function	1	1038.2×	0.004	CTNNB1
Regulation of CDH1 Function	1	951.7×	0.004	CTNNB1
Formation of axial mesoderm	1	815.7×	0.004	CTNNB1
Signaling by GSK3beta mutants	1	761.3×	0.004	CTNNB1
CTNNB1 S33 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
CTNNB1 S37 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
CTNNB1 S45 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
CTNNB1 T41 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
Formation of definitive endoderm	1	713.8×	0.004	CTNNB1
Beta-catenin phosphorylation cascade	1	671.8×	0.004	CTNNB1
Germ layer formation at gastrulation	1	671.8×	0.004	CTNNB1
Formation of the nephric duct	1	634.4×	0.004	CTNNB1
Specification of the neural plate border	1	634.4×	0.004	CTNNB1
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	571.0×	0.004	CTNNB1
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	519.1×	0.004	CTNNB1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.004	CTNNB1
Cardiogenesis	1	423.0×	0.004	CTNNB1
VEGFR2 mediated vascular permeability	1	407.9×	0.004	CTNNB1
Formation of paraxial mesoderm	1	407.9×	0.004	CTNNB1
Myogenesis	1	380.7×	0.004	CTNNB1
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.005	CTNNB1
RHO GTPases activate IQGAPs	1	346.1×	0.005	CTNNB1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	335.9×	0.005	CTNNB1

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
glial cell fate determination	1	16852.0×	0.001	CTNNB1
canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation	1	16852.0×	0.001	CTNNB1
cranial ganglion development	1	16852.0×	0.001	CTNNB1
neural plate development	1	8426.0×	0.001	CTNNB1
negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	8426.0×	0.001	CTNNB1
regulation of centriole-centriole cohesion	1	8426.0×	0.001	CTNNB1
negative regulation of mitotic cell cycle, embryonic	1	8426.0×	0.001	CTNNB1
regulation of timing of anagen	1	8426.0×	0.001	CTNNB1
positive regulation of branching involved in lung morphogenesis	1	8426.0×	0.001	CTNNB1
renal vesicle formation	1	8426.0×	0.001	CTNNB1
renal inner medulla development	1	8426.0×	0.001	CTNNB1
renal outer medulla development	1	8426.0×	0.001	CTNNB1
nephron tubule formation	1	8426.0×	0.001	CTNNB1
regulation of nephron tubule epithelial cell differentiation	1	8426.0×	0.001	CTNNB1
mesenchymal stem cell differentiation	1	8426.0×	0.001	CTNNB1
positive regulation of determination of dorsal identity	1	8426.0×	0.001	CTNNB1
astrocyte-dopaminergic neuron signaling	1	5617.3×	0.001	CTNNB1
regulation of fibroblast proliferation	1	5617.3×	0.001	CTNNB1
oviduct development	1	5617.3×	0.001	CTNNB1
lung induction	1	5617.3×	0.001	CTNNB1
positive regulation of epithelial cell proliferation involved in prostate gland development	1	5617.3×	0.001	CTNNB1
fungiform papilla formation	1	5617.3×	0.001	CTNNB1
regulation of centromeric sister chromatid cohesion	1	5617.3×	0.001	CTNNB1
regulation of secondary heart field cardioblast proliferation	1	4213.0×	0.001	CTNNB1
metanephros morphogenesis	1	4213.0×	0.001	CTNNB1
positive regulation of heparan sulfate proteoglycan biosynthetic process	1	4213.0×	0.001	CTNNB1
embryonic skeletal limb joint morphogenesis	1	4213.0×	0.001	CTNNB1
central nervous system vasculogenesis	1	3370.4×	0.001	CTNNB1
genitalia morphogenesis	1	3370.4×	0.001	CTNNB1
epithelial cell differentiation involved in prostate gland development	1	3370.4×	0.001	CTNNB1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

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
CTNNB1	DITHIAZANINE IODIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTNNB1	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CTNNB1	361	Binding:358, Functional:3

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CTNNB1	361

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

4 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)
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CTNNB1
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	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
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05549167	PHASE3	RECRUITING	Efficacy and Safety of Sirolimus in Children and Adolescents With Juvenile Nasopharyngeal Angiofibroma (JNA)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SIROLIMUS	4	1