Juvenile hyaline fibromatosis

Summary

Juvenile hyaline fibromatosis (MONDO:0016071) is a disease caused by ANTXR2 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ANTXR2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 2
• Phenotypes (HPO): 16
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		70	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000271	Abnormality of the face	Very frequent (80-99%)
HP:0000929	Abnormal skull morphology	Very frequent (80-99%)
HP:0000940	Abnormal diaphysis morphology	Very frequent (80-99%)
HP:0001482	Subcutaneous nodule	Very frequent (80-99%)
HP:0001595	Abnormality of the hair	Very frequent (80-99%)
HP:0200034	Papule	Very frequent (80-99%)
HP:0001522	Death in infancy	Frequent (30-79%)
HP:0008065	Aplasia/Hypoplasia of the skin	Frequent (30-79%)
HP:0200042	Skin ulcer	Frequent (30-79%)
HP:0000169	Gingival fibromatosis	Occasional (5-29%)
HP:0000212	Gingival overgrowth	Occasional (5-29%)
HP:0001387	Joint stiffness	Occasional (5-29%)
HP:0002797	Osteolysis	Occasional (5-29%)
HP:0003202	Skeletal muscle atrophy	Occasional (5-29%)
HP:0005876	Progressive flexion contractures	Occasional (5-29%)
HP:0011024	Abnormality of the gastrointestinal tract	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile hyaline fibromatosis
Mondo ID	MONDO:0016071
Orphanet	2028
ICD-11	1890146024
NCIT	C98297
SNOMED CT	238861002
UMLS	C2745948
MedGen	411197
GARD	0016583
Is cancer (heuristic)	no

Also known as: mesenchymal dysplasia · Molluscum fibrosum · Murray-Puretic-Drescher syndrome · Puretic syndrome

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › skin neoplasm › dermis tumor › juvenile hyaline fibromatosis

Related subtypes (7): cutaneous granular cell tumor, skin glomus tumor, leiomyoma cutis, malignant dermis tumor, cutaneous fibrous histiocytoma, cutaneous mastocytosis, angioma serpiginosum

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/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
974886	NM_058172.6(ANTXR2):c.652T>C (p.Cys218Arg)	ANTXR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3895547	NC_000004.11:g.(?80822299)(80906018_80929674)del	ANTXR2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
ANTXR2	Definitive	Autosomal recessive	hyaline fibromatosis syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANTXR2	Orphanet:2028	Juvenile hyaline fibromatosis
ANTXR2	Orphanet:2176	Infantile systemic hyalinosis

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
ANTXR2	HGNC:21732	ENSG00000163297	P58335	Anthrax toxin receptor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANTXR2	Anthrax toxin receptor 2	Necessary for cellular interactions with laminin and the extracellular matrix.

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)
ANTXR2	Other/Unknown	no		VWF_A, Anthrax_toxin_rcpt_C, Anthrax_toxin_rcpt_extracel

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
decidua	1
mucosa of stomach	1
smooth muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANTXR2	243	ubiquitous	marker	mucosa of stomach, decidua, smooth muscle tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANTXR2	1,270

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANTXR2	P58335	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Uptake and function of anthrax toxins	1	951.7×	0.001	ANTXR2

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
uterus development	1	802.5×	0.004	ANTXR2
collagen fibril organization	1	224.7×	0.005	ANTXR2
single fertilization	1	183.2×	0.005	ANTXR2

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
ANTXR2	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
ANTXR2	3	Binding:3

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	ANTXR2

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)
ANTXR2	3	—

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
NCT03196115	Not specified	WITHDRAWN	Biomarker for Hyaline Fibromatosis Syndrome (BioHFS)