Angel-shaped phalango-epiphyseal dysplasia

Summary

Angel-shaped phalango-epiphyseal dysplasia (MONDO:0007114) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0004220	Short middle phalanx of the 5th finger	Very frequent (80-99%)
HP:0005819	Short middle phalanx of finger	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0010034	Short 1st metacarpal	Very frequent (80-99%)
HP:0000668	Hypodontia	Frequent (30-79%)
HP:0000684	Delayed eruption of teeth	Frequent (30-79%)
HP:0001385	Hip dysplasia	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0008843	Hip osteoarthritis	Frequent (30-79%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0002750	Delayed skeletal maturation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Angel-shaped phalango-epiphyseal dysplasia
Mondo ID	MONDO:0007114
MeSH	C536361
OMIM	105835
Orphanet	63442
ICD-11	1095628863
SNOMED CT	720984008
UMLS	C1739384
MedGen	366028
GARD	0000671
MedDRA	10066017
Is cancer (heuristic)	no

Also known as: Angel shaped phalangoepiphyseal dysplasia · Angel-shaped phalangoepiphyseal dysplasia · ASPED

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › acromelic dysplasia › Angel-shaped phalango-epiphyseal dysplasia

Related subtypes (17): geleophysic dysplasia, Acromicric dysplasia, pseudohypoparathyroidism type 1A, Myhre syndrome, Leri pleonosteosis, peripheral dysostosis, short-rib thoracic dysplasia 9 with or without polydactyly, terminal osseous dysplasia-pigmentary defects syndrome, intellectual disability-balding-patella luxation-acromicria syndrome, acrocapitofemoral dysplasia, pseudohypoparathyroidism type 1C, pseudopseudohypoparathyroidism, short stature-brachydactyly-obesity-global developmental delay syndrome, trichorhinophalangeal syndrome, Weill-Marchesani syndrome, craniofacial conodysplasia, acrodysostosis

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: 20 · Orphanet: 9 · 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
GDF5	Definitive	Autosomal recessive	acromesomelic dysplasia 2A	20

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GDF5	Orphanet:2098	Acromesomelic dysplasia, Grebe type
GDF5	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
GDF5	Orphanet:3237	Multiple synostoses syndrome
GDF5	Orphanet:3250	Proximal symphalangism
GDF5	Orphanet:63442	Angel-shaped phalango-epiphyseal dysplasia
GDF5	Orphanet:93384	Brachydactyly type C
GDF5	Orphanet:93388	Brachydactyly type A1
GDF5	Orphanet:93396	Brachydactyly type A2
GDF5	Orphanet:968	Acromesomelic dysplasia, Hunter-Thompson 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
GDF5	HGNC:4220	ENSG00000125965	P43026	Growth/differentiation factor 5	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GDF5	Growth/differentiation factor 5	Growth factor involved in bone and cartilage formation.

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)
GDF5	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like

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
cartilage tissue	1
parotid gland	1
pericardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GDF5	116	broad	yes	parotid gland, pericardium, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GDF5	1,486

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GDF5	P43026	15

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
Molecules associated with elastic fibres	1	308.6×	0.003	GDF5

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
ossification involved in bone remodeling	1	5617.3×	0.002	GDF5
chondroblast differentiation	1	3370.4×	0.002	GDF5
hindlimb morphogenesis	1	2808.7×	0.002	GDF5
negative regulation of mesenchymal cell apoptotic process	1	2407.4×	0.002	GDF5
forelimb morphogenesis	1	2106.5×	0.002	GDF5
mesenchymal cell apoptotic process	1	1532.0×	0.002	GDF5
positive regulation of chondrocyte differentiation	1	802.5×	0.003	GDF5
negative regulation of chondrocyte differentiation	1	674.1×	0.003	GDF5
regulation of multicellular organism growth	1	648.1×	0.003	GDF5
positive regulation of BMP signaling pathway	1	455.5×	0.004	GDF5
embryonic limb morphogenesis	1	401.2×	0.004	GDF5
positive regulation of SMAD protein signal transduction	1	383.0×	0.004	GDF5
chondrocyte differentiation	1	300.9×	0.005	GDF5
response to mechanical stimulus	1	300.9×	0.005	GDF5
negative regulation of epithelial cell proliferation	1	290.6×	0.005	GDF5
BMP signaling pathway	1	200.6×	0.006	GDF5
positive regulation of neuron differentiation	1	198.3×	0.006	GDF5
transforming growth factor beta receptor signaling pathway	1	159.0×	0.007	GDF5
negative regulation of neuron apoptotic process	1	110.9×	0.009	GDF5
cell-cell signaling	1	69.6×	0.014	GDF5

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GDF5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	GDF5

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)
GDF5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.