Spondyloepimetaphyseal dysplasia

Summary

Spondyloepimetaphyseal dysplasia (MONDO:0100510) is a disease (an umbrella term covering 23 Mondo subtypes) with 3 cohort genes.

At a glance

• Umbrella term: 23 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepimetaphyseal dysplasia
Mondo ID	MONDO:0100510
DOID	DOID:0080027
SNOMED CT	254062008
UMLS	C0432211
MedGen	609408
GARD	0026258
Is cancer (heuristic)	no

Also known as: SEMD · spondylo-epi-(meta)-physeal dysplasia

Data availability: 4 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 23 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 › spondyloepimetaphyseal 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, spondyloepiphyseal dysplasia, thanatophoric dysplasia, Blount disease, osteogenesis imperfecta, achondrogenesis, acromesomelic dysplasia, neonatal osteosclerotic dysplasia, Akaba Hayasaka syndrome, Fairbank disease, mesomelic dysplasia, cleidocranial dysplasia 2, arterial tortuosity-bone fragility syndrome, linkeropathy

Subtypes (23): spondyloepimetaphyseal dysplasia-hypotrichosis syndrome, spondyloepimetaphyseal dysplasia, Maroteaux type, spondyloepimetaphyseal dysplasia, Strudwick type, spondyloepimetaphyseal dysplasia, sponastrime type, spondyloepimetaphyseal dysplasia, Irapa type, spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome, spondyloepimetaphyseal dysplasia, Bieganski type, spondyloepimetaphyseal dysplasia-abnormal dentition syndrome, spondyloepimetaphyseal dysplasia, Missouri type, spondyloepimetaphyseal dysplasia, Shohat type, spondyloepimetaphyseal dysplasia, matrilin-3 type, spondyloepimetaphyseal dysplasia, Genevieve type, spondyloepimetaphyseal dysplasia, aggrecan type, spondyloepimetaphyseal dysplasia, Handigodu type, spondyloepimetaphyseal dysplasia, Isidor type, spondyloepimetaphyseal dysplasia, PAPSS2 type, spondyloepimetaphyseal dysplasia with joint laxity, spondyloepimetaphyseal dysplasia, Krakow type, spondyloepimetaphyseal dysplasia, Isidor-Toutain type, spondyloepimetaphyseal dysplasia, di rocco type, COL2A1-related spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia, Guo-Campeau type, spondyloepimetaphyseal dysplasia, Li-Shao-Li 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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
689800	NM_000977.4(RPL13):c.477+1G>T	RPL13	Pathogenic	criteria provided, single submitter
689801	NM_000977.4(RPL13):c.477+2T>C	RPL13	Pathogenic	no assertion criteria provided
689802	NM_000977.4(RPL13):c.477+1G>A	RPL13	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
689803	NM_000977.4(RPL13):c.548G>T (p.Arg183Leu)	RPL13	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 3 · 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
BNIP1	Moderate	Autosomal recessive	spondyloepimetaphyseal dysplasia
CCN2	Limited	Autosomal recessive	kyphomelic dysplasia	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCN2	Orphanet:220393	Diffuse cutaneous systemic sclerosis
CCN2	Orphanet:220402	Limited cutaneous systemic sclerosis
RPL13	Orphanet:370015	Spondyloepimetaphyseal dysplasia, Isidor-Toutain type

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BNIP1	HGNC:1082	ENSG00000113734	Q12981	Vesicle transport protein SEC20	gencc
CCN2	HGNC:2500	ENSG00000118523	P29279	CCN family member 2	gencc
RPL13	HGNC:10303	ENSG00000167526	P26373	Large ribosomal subunit protein eL13	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BNIP1	Vesicle transport protein SEC20	As part of a SNARE complex may be involved in endoplasmic reticulum membranes fusion and be required for the maintenance of endoplasmic reticulum organization.
CCN2	CCN family member 2	Major connective tissue mitoattractant secreted by vascular endothelial cells.
RPL13	Large ribosomal subunit protein eL13	Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BNIP1	Other/Unknown	no		Sec20, Sec20_C
CCN2	Other/Unknown	no		IGFBP-like, TSP1_rpt, VWF_dom
RPL13	Other/Unknown	no		Ribosomal_eL13, Ribosomal_eL13_CS

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
oocyte	1
secondary oocyte	1
ascending aorta	1
thoracic aorta	1
tibia	1
left ovary	1
right ovary	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BNIP1	226	ubiquitous	marker	secondary oocyte, oocyte, diaphragm
CCN2	270	ubiquitous	marker	tibia, ascending aorta, thoracic aorta
RPL13	311	ubiquitous	marker	right uterine tube, right ovary, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL13	4,612
CCN2	3,887
BNIP1	1,672

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL13	P26373	191

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BNIP1	Q12981	80.86
CCN2	P29279	78.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates YAP1-mediated transcription	1	475.8×	0.041	CCN2
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	253.8×	0.041	CCN2
Transcriptional regulation by RUNX3	1	90.6×	0.041	CCN2
Golgi-to-ER retrograde transport	1	44.3×	0.041	BNIP1
Peptide chain elongation	1	42.3×	0.041	RPL13
Viral mRNA Translation	1	42.3×	0.041	RPL13
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	41.8×	0.041	RPL13
Selenocysteine synthesis	1	40.1×	0.041	RPL13
Eukaryotic Translation Termination	1	40.1×	0.041	RPL13
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	39.2×	0.041	RPL13
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	39.2×	0.041	RPL13
Formation of a pool of free 40S subunits	1	37.3×	0.041	RPL13
COPI-dependent Golgi-to-ER retrograde traffic	1	37.0×	0.041	BNIP1
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	37.0×	0.041	RPL13
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	1	35.6×	0.041	RPL13
Intra-Golgi and retrograde Golgi-to-ER traffic	1	34.9×	0.041	BNIP1
L13a-mediated translational silencing of Ceruloplasmin expression	1	33.7×	0.041	RPL13
SRP-dependent cotranslational protein targeting to membrane	1	33.4×	0.041	RPL13
GTP hydrolysis and joining of the 60S ribosomal subunit	1	33.4×	0.041	RPL13
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1	32.5×	0.041	RPL13
Regulation of expression of SLITs and ROBOs	1	23.1×	0.055	RPL13
Major pathway of rRNA processing in the nucleolus and cytosol	1	20.6×	0.059	RPL13
Membrane Trafficking	1	12.4×	0.092	BNIP1
Vesicle-mediated transport	1	11.6×	0.094	BNIP1
RNA Polymerase II Transcription	1	7.5×	0.138	CCN2
Gene expression (Transcription)	1	6.0×	0.165	CCN2
Generic Transcription Pathway	1	5.0×	0.186	CCN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
apoptotic process in response to mitochondrial fragmentation	1	5617.3×	0.007	BNIP1
endoplasmic reticulum membrane fusion	1	1123.5×	0.016	BNIP1
response to oxygen-glucose deprivation	1	702.2×	0.018	BNIP1
regulation of chondrocyte differentiation	1	468.1×	0.018	CCN2
chondrocyte proliferation	1	351.1×	0.018	CCN2
DNA biosynthetic process	1	267.5×	0.018	CCN2
cartilage condensation	1	255.3×	0.018	CCN2
execution phase of apoptosis	1	255.3×	0.018	BNIP1
blastocyst development	1	224.7×	0.018	RPL13
tissue homeostasis	1	187.2×	0.020	CCN2
response to starvation	1	156.0×	0.020	BNIP1
reactive oxygen species metabolic process	1	156.0×	0.020	CCN2
endoplasmic reticulum organization	1	140.4×	0.020	BNIP1
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	112.3×	0.021	BNIP1
response to activity	1	108.0×	0.021	BNIP1
positive regulation of stress fiber assembly	1	104.0×	0.021	CCN2
chondrocyte differentiation	1	100.3×	0.021	CCN2
fibroblast growth factor receptor signaling pathway	1	95.2×	0.021	CCN2
bone development	1	92.1×	0.021	RPL13
positive regulation of cell differentiation	1	89.2×	0.021	CCN2
response to wounding	1	73.9×	0.024	CCN2
epidermis development	1	70.2×	0.024	CCN2
lung development	1	66.1×	0.024	CCN2
cytoplasmic translation	1	61.7×	0.025	RPL13
cell-matrix adhesion	1	54.5×	0.025	CCN2
positive regulation of JNK cascade	1	54.5×	0.025	CCN2
integrin-mediated signaling pathway	1	53.5×	0.025	CCN2
osteoblast differentiation	1	40.4×	0.032	CCN2
translation	1	34.2×	0.037	RPL13
positive regulation of ERK1 and ERK2 cascade	1	28.4×	0.043	CCN2

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPL13	1	4
BNIP1	0	0
CCN2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL13

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPL13	90	Binding:90
CCN2	16	Binding:16

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPL13
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	2	BNIP1, CCN2

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)
BNIP1	0	—
CCN2	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.