Spondyloepiphyseal dysplasia

Summary

Spondyloepiphyseal dysplasia (MONDO:0016761) is a disease (an umbrella term covering 44 Mondo subtypes) with 5 cohort genes.

At a glance

• Umbrella term: 44 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepiphyseal dysplasia
Mondo ID	MONDO:0016761
Orphanet	252
DOID	DOID:0112280
ICD-10-CM	Q77.7
UMLS	C0038015
MedGen	20916
GARD	0007687
MedDRA	10062920
Is cancer (heuristic)	no

Also known as: SED · spondyloepiphyseal dysplasia

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 44 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 › spondyloepiphyseal dysplasia

Related subtypes (49): 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, 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

Subtypes (44): hip dysplasia, Beukes type, spondyloepiphyseal dysplasia with congenital joint dislocations, Marshall syndrome, metatropic dysplasia, spondyloepiphyseal dysplasia with punctate corneal dystrophy, spondyloepiphyseal dysplasia, MacDermot type, progressive pseudorheumatoid arthropathy of childhood, otospondylomegaepiphyseal dysplasia, Dyggve-Melchior-Clausen disease, dyssegmental dysplasia, Rolland-Desbuquois type, Silverman-Handmaker type dyssegmental dysplasia, Wolcott-Rallison syndrome, Schimke immuno-osseous dysplasia, Richieri Costa-da Silva syndrome, Schwartz-Jampel syndrome, X-linked spondyloepimetaphyseal dysplasia, CODAS syndrome, spondyloepiphyseal dysplasia, Reardon type, brachyolmia-amelogenesis imperfecta syndrome, spondyloepiphyseal dysplasia with coronal craniosynostosis, cataracts, cleft palate, and intellectual disability, anauxetic dysplasia, spondyloepiphyseal dysplasia, Kimberley type, spondyloepiphyseal dysplasia, Cantu type, Ehlers-Danlos syndrome, spondylocheirodysplastic type, spondylo-megaepiphyseal-metaphyseal dysplasia, brachydactylous dwarfism, Mseleni type, TMEM165-congenital disorder of glycosylation, Steel syndrome, cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, Roifman syndrome, progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome, even-plus syndrome, Smith-McCort dysplasia, cono-spondylar dysplasia, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, Stickler syndrome, spondyloepiphyseal dysplasia tarda, spondyloepiphyseal dysplasia, kondo-fu type, spondyloepiphyseal dysplasia, nishimura type, immunoskeletal dysplasia with neurodevelopmental abnormalities, COL2A1-related spondyloepiphyseal dysplasia, MIR140-related spondyloepiphyseal dysplasia, MGP-related spondyloepiphyseal dysplasia, spondyloepiphyseal dysplasia, Holling type

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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3384000	NM_001369268.1(ACAN):c.1513del (p.Ala505fs)	ACAN	Pathogenic	criteria provided, single submitter
940	NM_000404.4(GLB1):c.1313G>A (p.Gly438Glu)	GLB1	Pathogenic	criteria provided, multiple submitters, no conflicts
3384001	NM_001369268.1(ACAN):c.6946+1G>T	ACAN	Likely pathogenic	criteria provided, single submitter
666963	NM_080605.4(B3GALT6):c.763C>T (p.Gln255Ter)	B3GALT6	Likely pathogenic	criteria provided, single submitter
1373923	NM_000900.5(MGP):c.56G>T (p.Cys19Phe)	MGP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 12 · 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
RPL13	Strong	Autosomal dominant	spondyloepimetaphyseal dysplasia, Isidor-Toutain type	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPL13	Orphanet:370015	Spondyloepimetaphyseal dysplasia, Isidor-Toutain type
B3GALT6	Orphanet:536467	B3GALT6-related spondylodysplastic Ehlers-Danlos syndrome
B3GALT6	Orphanet:642099	Spondyloepimetaphyseal dysplasia with joint laxity, Beighton type
ACAN	Orphanet:171866	Spondyloepimetaphyseal dysplasia, aggrecan type
ACAN	Orphanet:251262	Familial osteochondritis dissecans
ACAN	Orphanet:435804	Short stature-advanced bone age-early-onset osteoarthritis syndrome
ACAN	Orphanet:93283	Spondyloepiphyseal dysplasia, Kimberley type
GLB1	Orphanet:309310	Mucopolysaccharidosis type 4B
GLB1	Orphanet:79255	GM1 gangliosidosis type 1
GLB1	Orphanet:79256	GM1 gangliosidosis type 2
GLB1	Orphanet:79257	GM1 gangliosidosis type 3
MGP	Orphanet:85202	Keutel syndrome

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL13	HGNC:10303	ENSG00000167526	P26373	Large ribosomal subunit protein eL13	gencc
B3GALT6	HGNC:17978	ENSG00000176022	Q96L58	Beta-1,3-galactosyltransferase 6	clinvar
ACAN	HGNC:319	ENSG00000157766	P16112	Aggrecan core protein	clinvar
GLB1	HGNC:4298	ENSG00000170266	P16278	Beta-galactosidase	clinvar
MGP	HGNC:7060	ENSG00000111341	P08493	Matrix Gla protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL13	Large ribosomal subunit protein eL13	Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
B3GALT6	Beta-1,3-galactosyltransferase 6	Beta-1,3-galactosyltransferase that transfers galactose from UDP-galactose to substrates with a terminal beta-linked galactose residue.
ACAN	Aggrecan core protein	This proteoglycan is a major component of extracellular matrix of cartilagenous tissues.
GLB1	Beta-galactosidase	Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.
MGP	Matrix Gla protein	Associates with the organic matrix of bone and cartilage.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.4

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
Complement	1	53.6×	0.056
Enzyme (other)	1	2.4×	0.530
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL13	Other/Unknown	no		Ribosomal_eL13, Ribosomal_eL13_CS
B3GALT6	Enzyme (other)	yes	2.4.1.134	Glyco_trans_31
ACAN	Complement	yes		Sushi_SCR_CCP_dom, Link_dom, EGF
GLB1	Other/Unknown	no		Glycoside_Hdrlase_35, Galactose-bd-like_sf, GH_hydrolase_sf
MGP	Other/Unknown	no		GLA_domain, Osteocalcin/MGP, MGP

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	2
descending thoracic aorta	2
left ovary	1
right ovary	1
right uterine tube	1
Brodmann (1909) area 23	1
endothelial cell	1
tibia	1
monocyte	1
mononuclear cell	1
stromal cell of endometrium	1
ascending aorta	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL13	311	ubiquitous	marker	right uterine tube, right ovary, left ovary
B3GALT6	236	ubiquitous	yes	Brodmann (1909) area 23, endothelial cell, cartilage tissue
ACAN	181	broad	marker	tibia, cartilage tissue, descending thoracic aorta
GLB1	258	ubiquitous	marker	monocyte, mononuclear cell, stromal cell of endometrium
MGP	274	ubiquitous	marker	ascending aorta, thoracic aorta, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL13	4,612
ACAN	2,200
MGP	1,645
GLB1	1,578
B3GALT6	797

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL13	P26373	191
GLB1	P16278	8
ACAN	P16112	4
MGP	P08493	3
B3GALT6	Q96L58	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Keratan sulfate degradation	2	356.9×	5e-04	ACAN, GLB1
Heparan sulfate/heparin (HS-GAG) metabolism	2	271.9×	5e-04	B3GALT6, GLB1
Glycosaminoglycan metabolism	2	109.8×	0.002	B3GALT6, GLB1
Diseases of glycosylation	2	65.6×	0.005	B3GALT6, GLB1
Metabolism of carbohydrates and carbohydrate derivatives	2	60.1×	0.005	B3GALT6, GLB1
MPS IV - Morquio syndrome B (Keratin metabolism)	1	1427.5×	0.006	GLB1
MPS IV - Morquio syndrome B (CS/DS degradation)	1	1427.5×	0.006	GLB1
Diseases of metabolism	2	40.2×	0.006	B3GALT6, GLB1
Defective NEU1 causes sialidosis	1	713.8×	0.009	GLB1
Mucopolysaccharidoses	1	475.8×	0.012	GLB1
Defective CHST6 causes MCDC1	1	356.9×	0.012	ACAN
Defective ST3GAL3 causes MCT12 and EIEE15	1	356.9×	0.012	ACAN
Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)	1	356.9×	0.012	ACAN
Chondroitin sulfate/dermatan sulfate metabolism	1	237.9×	0.017	B3GALT6
Diseases of carbohydrate metabolism	1	203.9×	0.018	GLB1
Diseases associated with glycosaminoglycan metabolism	1	190.3×	0.018	B3GALT6
Diseases associated with N-glycosylation of proteins	1	158.6×	0.021	GLB1
Defective B3GALT6 causes EDSP2 and SEMDJL1	1	142.8×	0.021	B3GALT6
CS/DS degradation	1	135.9×	0.021	GLB1
Keratan sulfate/keratin metabolism	1	124.1×	0.021	GLB1
HS-GAG degradation	1	124.1×	0.021	GLB1
Glycosaminoglycan-protein linkage region biosynthesis	1	98.5×	0.025	B3GALT6
Keratan sulfate biosynthesis	1	95.2×	0.025	ACAN
Sialic acid metabolism	1	81.6×	0.028	GLB1
Glycosphingolipid metabolism	1	75.1×	0.028	GLB1
Synthesis of substrates in N-glycan biosythesis	1	73.2×	0.028	GLB1
Glycosphingolipid catabolism	1	73.2×	0.028	GLB1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	51.9×	0.038	GLB1
Sphingolipid metabolism	1	42.0×	0.046	GLB1
ECM proteoglycans	1	37.6×	0.048	ACAN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to cortisone	1	1685.2×	0.008	GLB1
keratan sulfate proteoglycan catabolic process	1	1123.5×	0.008	GLB1
response to Thyroglobulin triiodothyronine	1	1123.5×	0.008	GLB1
glycosaminoglycan-protein linkage region biosynthetic process	1	842.6×	0.008	B3GALT6
galactose catabolic process	1	561.7×	0.009	GLB1
ganglioside catabolic process	1	374.5×	0.011	GLB1
dermatan sulfate proteoglycan biosynthetic process	1	337.0×	0.011	B3GALT6
glycoprotein catabolic process	1	210.7×	0.015	GLB1
glycosaminoglycan biosynthetic process	1	168.5×	0.015	B3GALT6
proteoglycan biosynthetic process	1	168.5×	0.015	B3GALT6
cartilage condensation	1	153.2×	0.015	MGP
regulation of bone mineralization	1	146.5×	0.015	MGP
blastocyst development	1	134.8×	0.015	RPL13
chondroitin sulfate proteoglycan biosynthetic process	1	124.8×	0.015	B3GALT6
heparan sulfate proteoglycan biosynthetic process	1	112.3×	0.015	B3GALT6
bone development	1	55.2×	0.029	RPL13
ossification	1	45.5×	0.032	MGP
protein O-linked glycosylation	1	44.9×	0.032	B3GALT6
cytoplasmic translation	1	37.0×	0.037	RPL13
carbohydrate metabolic process	1	27.2×	0.047	GLB1
skeletal system development	1	25.1×	0.048	ACAN
central nervous system development	1	23.1×	0.050	ACAN
translation	1	20.6×	0.054	RPL13
cell adhesion	1	7.5×	0.137	ACAN
proteolysis	1	6.8×	0.143	ACAN
cell differentiation	1	5.8×	0.160	MGP

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
RPL13	GENTAMICIN SULFATE
GLB1	MIGALASTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPL13	1	4
GLB1	1	4
B3GALT6	0	0
ACAN	0	0
MGP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL13
MIGALASTAT	4	GLB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GLB1	124	Binding:123, ADMET:1
RPL13	90	Binding:90

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
B3GALT6	2.4.1.134	galactosylxylosylprotein 3-beta-galactosyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GLB1	124

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 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)
GENTAMICIN SULFATE	4	RPL13
MIGALASTAT	4	GLB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RPL13, GLB1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	B3GALT6, ACAN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MGP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
B3GALT6	0	—
ACAN	0	—
MGP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.