Acromelic dysplasia

Summary

Acromelic dysplasia (MONDO:0019695) is a disease (an umbrella term covering 18 Mondo subtypes) caused by GDF5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GDF5 (GenCC Strong)
• Umbrella term: 18 Mondo subtypes
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acromelic dysplasia
Mondo ID	MONDO:0019695
Orphanet	93436
ICD-11	177141175
UMLS	C4736195
MedGen	1843369
GARD	0019194
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 18 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › acromelic dysplasia

Related subtypes (118): osteochondrodysplasia, diaphyseal medullary stenosis-bone malignancy syndrome, fibular aplasia-ectrodactyly syndrome, cerebrocostomandibular syndrome, cleidorhizomelic syndrome, dyschondrosteosis-nephritis syndrome, dysplasia epiphysealis hemimelica, carpotarsal osteochondromatosis, Camurati-Engelmann disease, genochondromatosis, autosomal dominant osteosclerosis, Worth type, coxopodopatellar syndrome, Lenz-Majewski hyperostotic dwarfism, delayed membranous cranial ossification, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, oculodentodigital dysplasia, Ollier disease, osteoglophonic dysplasia, parietal foramina with cleidocranial dysplasia, chondromalacia patellae, Currarino triad, Proteus syndrome, brachydactyly-elbow wrist dysplasia syndrome, tricho-dento-osseous syndrome, bird headed-dwarfism, Montreal type, Yunis-Varon syndrome, split hand-foot malformation 1 with sensorineural hearing loss, ghosal hematodiaphyseal dysplasia, hyperostosis corticalis generalisata, Larsen-like syndrome, B3GAT3 type, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal acroscyphodysplasia, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, familial osteodysplasia, Anderson type, pseudodiastrophic dysplasia, rhizomelic syndrome, Urbach type, Richieri Costa-Pereira syndrome, craniometadiaphyseal dysplasia, wormian bone type, Weaver syndrome, SHOX-related short stature, craniofrontonasal syndrome, Eiken syndrome, 2q37 microdeletion syndrome, skeletal dysplasia-epilepsy-short stature syndrome, rhizomelic dysplasia, Patterson-Lowry type, pelvic dysplasia-arthrogryposis of lower limbs syndrome, Marshall-Smith syndrome, baby rattle pelvis dysplasia, metaphyseal dysplasia, Braun-Tinschert type, genitopatellar syndrome, osteofibrous dysplasia, Larsen-like osseous dysplasia-short stature syndrome, pancreatic insufficiency-anemia-hyperostosis syndrome, microcephalic primordial dwarfism due to ZNF335 deficiency, Hartsfield-Bixler-Demyer syndrome, colobomatous microphthalmia-rhizomelic dysplasia syndrome, Tatton-Brown-Rahman overgrowth syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, Catel-Manzke syndrome, cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome, complex lethal osteochondrodysplasia, amniotic band syndrome, metaphyseal anadysplasia, syndromic craniosynostosis, thin ribs-tubular bones-dysmorphism syndrome, dysplasia of head of femur, Meyer type, epimetaphyseal skeletal dysplasia, melorheostosis with osteopoikilosis, Cole-Carpenter syndrome, spondylometaphyseal dysplasia, omodysplasia, Bruck syndrome, osteopetrosis, congenital absence of upper arm and forearm with hand present, congenital absence of thigh and lower leg with foot present, congenital absence of both forearm and hand, congenital absence of both lower leg and foot, acheiria, apodia, chondroectodermal dysplasia with night blindness, TRPV4-related bone disorder, adactyly of foot, short stature-advanced bone age-early-onset osteoarthritis syndrome, McCune-Albright syndrome, parietal foramina, Sotos syndrome, dysspondyloenchondromatosis, autosomal recessive cutis laxa type 2, FGFR3-related chondrodysplasia, filamin-related bone disorder, short rib dysplasia, spondylodysplastic dysplasia, bent bone dysplasia, chondrodysplasia punctata, primary osteolysis, non-syndromic limb reduction defect, Robinow syndrome, synpolydactyly, acrocoxomesomelic dysplasia, bone dysplasia Moore type, bone dysplasia corpus callosum agenesis, type 2 collagenopathy, LRP5-related primary osteoporosis, SLC26A2-related skeletal dysplasia, COMP-related skeletal dysplasia, primordial dwarfism and slender bone disorder, polydactyly-syndactyly-triphalangism, lysosomal storage disease with skeletal involvement, abnormal mineralization disorder, calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia, de la Chapelle dysplasia, mesomelic dysplasia-digital anomalies-intellectual disability syndrome, proximal femoral focal deficiency, rhizomelic dysplasia, Ain-Naz type, craniotubular dysplasia, Ikegawa type, TRIP11-related skeletal dysplasia, FAM111A-related skeletal dysplasia

Subtypes (18): geleophysic dysplasia, Acromicric dysplasia, pseudohypoparathyroidism type 1A, Angel-shaped phalango-epiphyseal dysplasia, 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.