Osteochondrodysplasia

Summary

Osteochondrodysplasia (MONDO:0005516) is a disease (an umbrella term covering 50 Mondo subtypes) with 2 cohort genes and 9 clinical trials.

At a glance

• Umbrella term: 50 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 13
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	osteochondrodysplasia
Mondo ID	MONDO:0005516
EFO	EFO:0005571
MeSH	D010009
DOID	DOID:2256
NCIT	C84978
SNOMED CT	105985007
UMLS	C0029422
MedGen	10495
Is cancer (heuristic)	no

Also known as: cartilage development disorder · congenital anomaly of cartilage · congenital skeletal dysplasia · osteochondrodysplasia · skeletal dysplasia

Data availability: 13 ClinVar variants · 1 GenCC gene-disease record · 2 cell lines.

Disease family

An umbrella term covering 50 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia

Related subtypes (8): developmental dysplasia of the hip, brachydactyly-elbow wrist dysplasia syndrome, spondylocarpotarsal synostosis syndrome, odontoid hypoplasia, dysostosis, segmental odontomaxillary dysplasia, angioosteohypotrophic syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type

Subtypes (50): atelosteogenesis, midface dysplasia, Kashin-Beck disease, achondroplasia, Boomerang dysplasia, campomelic dysplasia, cleidocranial dysplasia 1, Leri-Weill dyschondrosteosis, hypochondroplasia, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, Kniest dysplasia, pseudoachondroplasia, ulna metaphyseal dysplasia syndrome, acheiropody, microcephalic osteodysplastic primordial dwarfism type I, microcephalic osteodysplastic primordial dwarfism type II, bone dysplasia, lethal Holmgren type, cleidocranial dysplasia, recessive form, diastrophic dysplasia, hypertrichotic osteochondrodysplasia Cantu type, lethal Kniest-like dysplasia, metaphyseal chondrodysplasia, Kaitila type, metaphyseal chondrodysplasia, Spahr type, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, pycnodysostosis, pyknoachondrogenesis, Pyle disease, schneckenbecken dysplasia, mesomelia-synostoses syndrome, lethal chondrodysplasia, Seller type, acrocapitofemoral dysplasia, brachyolmia, Desbuquois dysplasia, fibrochondrogenesis, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, spondyloepimetaphyseal dysplasia, cleidocranial dysplasia 2, arterial tortuosity-bone fragility syndrome, linkeropathy

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

13 retrieved; paginated sample, class counts are floors:

7 pathogenic/likely pathogenic, 4 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
371708	NM_000112.4(SLC26A2):c.1955_1958del (p.Asp652fs)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4099	NM_000112.4(SLC26A2):c.1535C>A (p.Thr512Lys)	SLC26A2	Pathogenic	criteria provided, multiple submitters, no conflicts
550616	NM_000112.4(SLC26A2):c.1987G>A (p.Gly663Arg)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551189	NM_000112.4(SLC26A2):c.870del (p.Thr289_Trp290insTer)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
554186	NM_000112.4(SLC26A2):c.1817del (p.Pro606fs)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56016	NM_000112.4(SLC26A2):c.1650del (p.Ser551fs)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56027	NM_000112.4(SLC26A2):c.700-1G>C	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
960730	NM_000112.4(SLC26A2):c.1421del (p.Leu474fs)	SLC26A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2503883	NM_000112.4(SLC26A2):c.1034T>A (p.Leu345Ter)	SLC26A2	Likely pathogenic	criteria provided, single submitter
4094	NM_000112.4(SLC26A2):c.2033G>T (p.Gly678Val)	SLC26A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4096	NM_000112.4(SLC26A2):c.1361A>C (p.Gln454Pro)	SLC26A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
555871	NM_000112.4(SLC26A2):c.776G>T (p.Gly259Val)	SLC26A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4090	NM_000112.4(SLC26A2):c.764G>A (p.Gly255Glu)	SLC26A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 4 · 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
GNPNAT1	Limited	Autosomal recessive	osteochondrodysplasia	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC26A2	Orphanet:56304	Atelosteogenesis type II
SLC26A2	Orphanet:628	Diastrophic dysplasia
SLC26A2	Orphanet:93298	Achondrogenesis type 1B
SLC26A2	Orphanet:93307	Multiple epiphyseal dysplasia type 4

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GNPNAT1	HGNC:19980	ENSG00000100522	Q96EK6	Glucosamine 6-phosphate N-acetyltransferase	gencc
SLC26A2	HGNC:10994	ENSG00000155850	P50443	Sulfate transporter	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC26A2	Sulfate transporter	Sulfate transporter which mediates sulfate uptake into chondrocytes in order to maintain adequate sulfation of proteoglycans which is needed for cartilage development.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	1	38.9×	0.051
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNPNAT1	Enzyme (other)	yes	2.3.1.4	GNAT_dom, Acyl_CoA_acyltransferase, GNPNAT1-like
SLC26A2	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic mucosa	2
mucosa of sigmoid colon	2
ileal mucosa	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNPNAT1	245	ubiquitous	marker	ileal mucosa, mucosa of sigmoid colon, colonic mucosa
SLC26A2	282	ubiquitous	marker	colonic mucosa, mucosa of sigmoid colon, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC26A2	1,793
GNPNAT1	1,208

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNPNAT1	Q96EK6	5
SLC26A2	P50443	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC26A2 causes chondrodysplasias	1	5710.0×	0.003	SLC26A2
Transport and metabolism of PAPS	1	815.7×	0.007	SLC26A2
Synthesis of UDP-N-acetyl-glucosamine	1	713.8×	0.007	GNPNAT1
Inorganic anion exchange by SLC26 transporters	1	634.4×	0.007	SLC26A2
Diseases associated with glycosaminoglycan metabolism	1	380.7×	0.010	SLC26A2
Cytosolic sulfonation of small molecules	1	259.6×	0.012	SLC26A2
Phase II - Conjugation of compounds	1	139.3×	0.019	SLC26A2
Glycosaminoglycan metabolism	1	109.8×	0.021	SLC26A2
SLC transporter disorders	1	102.0×	0.021	SLC26A2
Disorders of transmembrane transporters	1	69.6×	0.022	SLC26A2
Diseases of glycosylation	1	65.6×	0.022	SLC26A2
Biological oxidations	1	64.9×	0.022	SLC26A2
R-HSA-425393	1	64.9×	0.022	SLC26A2
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.022	SLC26A2
Diseases of metabolism	1	40.2×	0.031	SLC26A2
SLC-mediated transmembrane transport	1	29.6×	0.040	SLC26A2
Transport of small molecules	1	12.6×	0.087	SLC26A2
Disease	1	6.5×	0.155	SLC26A2
Metabolism	1	5.8×	0.165	SLC26A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
oxalate transport	1	1203.7×	0.003	SLC26A2
UDP-N-acetylglucosamine biosynthetic process	1	766.0×	0.003	GNPNAT1
sulfate transmembrane transport	1	601.9×	0.003	SLC26A2
chondrocyte proliferation	1	526.6×	0.003	SLC26A2
chondrocyte differentiation	1	150.5×	0.009	SLC26A2
chloride transmembrane transport	1	118.7×	0.010	SLC26A2
cellular response to leukemia inhibitory factor	1	79.5×	0.013	GNPNAT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
GNPNAT1	0	0
SLC26A2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GNPNAT1	2.3.1.4	glucosamine-phosphate N-acetyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	GNPNAT1, SLC26A2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GNPNAT1	0	—
SLC26A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06067425	PHASE2	TERMINATED	Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
NCT05846009	PHASE1	COMPLETED	A First-in-human Single and Repeated Dose Escalation Study of SAR442501 in Healthy Adults Subjects
NCT05247645	Not specified	RECRUITING	Data Collection of Patients With Rare Bone Diseases
NCT05876416	Not specified	RECRUITING	Decoding the Genetic Landscape of Skeletal Diseases
NCT05991609	Not specified	ACTIVE_NOT_RECRUITING	Extreme Morphology and Metabolic Health
NCT00001754	Not specified	COMPLETED	Study of Skeletal Disorders and Short Stature
NCT02762318	Not specified	TERMINATED	Identification and Characterization of Bone-related Genetic Variants in Families
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT06002373	Not specified	UNKNOWN	Assessment of Artificial Intelligence for Treatment Decision Recommendation of Adult Skeletal Class III Patients