spondyloepiphyseal dysplasia, Stanescu type

Summary

spondyloepiphyseal dysplasia, Stanescu type (MONDO:0014701) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 70

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepiphyseal dysplasia, Stanescu type
Mondo ID	MONDO:0014701
OMIM	616583
Orphanet	459051
DOID	DOID:0112281
UMLS	C4225273
MedGen	905084
GARD	0017812
Is cancer (heuristic)	no

Also known as: SED, Stanescu type · SEDSTN · spondyloepiphyseal dysplasia, Stanescu type

Data availability: 70 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › type 2 collagenopathy › spondyloepiphyseal dysplasia, Stanescu type

Related subtypes (13): Stickler syndrome type 1, multiple epiphyseal dysplasia, Beighton type, platyspondylic dysplasia, Torrance type, Kniest dysplasia, spondyloepiphyseal dysplasia congenita, spondyloepimetaphyseal dysplasia, Strudwick type, spondylometaphyseal dysplasia, Schmidt type, spondylometaphyseal dysplasia, ‘corner fracture’ type, achondrogenesis type II, spondyloperipheral dysplasia, spondyloepiphyseal dysplasia with metatarsal shortening, hypochondrogenesis, dysplasia of the proximal femoral epiphyses

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

70 retrieved; paginated sample, class counts are floors:

16 conflicting classifications of pathogenicity, 13 likely pathogenic, 10 pathogenic, 10 uncertain significance, 9 benign/likely benign, 6 pathogenic/likely pathogenic, 5 likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074468	NM_001844.5(COL2A1):c.1A>G (p.Met1Val)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1224342	NM_001844.5(COL2A1):c.3121G>A (p.Gly1041Ser)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1455692	NM_001844.5(COL2A1):c.2858del (p.Pro953fs)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17366	NM_001844.5(COL2A1):c.2965C>T (p.Arg989Cys)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17383	NM_001844.5(COL2A1):c.1693C>T (p.Arg565Cys)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17393	NM_001844.5(COL2A1):c.3508G>A (p.Gly1170Ser)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17395	NM_001844.5(COL2A1):c.1957C>T (p.Arg653Ter)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
195148	NM_001844.5(COL2A1):c.258C>A (p.Cys86Ter)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
195742	NM_001844.5(COL2A1):c.1510G>A (p.Gly504Ser)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
224878	NM_001844.5(COL2A1):c.619G>A (p.Gly207Arg)	COL2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
280745	NM_001844.5(COL2A1):c.1546G>A (p.Gly516Ser)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2859637	NM_001844.5(COL2A1):c.3085G>T (p.Gly1029Cys)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382798	NM_001844.5(COL2A1):c.3040G>A (p.Gly1014Arg)	COL2A1	Pathogenic	criteria provided, single submitter
449001	NM_001844.5(COL2A1):c.905C>T (p.Ala302Val)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
666308	NM_001844.5(COL2A1):c.3454G>C (p.Gly1152Arg)	COL2A1	Pathogenic	criteria provided, single submitter
988569	NM_001844.5(COL2A1):c.2059G>A (p.Gly687Ser)	COL2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320218	NM_001844.5(COL2A1):c.2167G>A (p.Gly723Ser)	COL2A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1516689	NM_001844.5(COL2A1):c.1618G>A (p.Gly540Ser)	COL2A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2585179	NM_001844.5(COL2A1):c.3256G>A (p.Gly1086Arg)	COL2A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382056	NM_001844.5(COL2A1):c.2771G>A (p.Gly924Glu)	COL2A1	Likely pathogenic	criteria provided, single submitter
3382294	NM_001844.5(COL2A1):c.3293G>A (p.Gly1098Glu)	COL2A1	Likely pathogenic	criteria provided, single submitter
3382404	NM_001844.5(COL2A1):c.3679_3680insAA (p.Gly1227fs)	COL2A1	Likely pathogenic	criteria provided, single submitter
3574632	NM_001844.5(COL2A1):c.1529G>T (p.Gly510Val)	COL2A1	Likely pathogenic	criteria provided, single submitter
3574633	NM_001844.5(COL2A1):c.1365+3A>C	COL2A1	Likely pathogenic	criteria provided, single submitter
3574634	NM_001844.5(COL2A1):c.917_918delinsA (p.Gly306fs)	COL2A1	Likely pathogenic	criteria provided, single submitter
446168	NM_001844.5(COL2A1):c.3655G>C (p.Asp1219His)	COL2A1	Likely pathogenic	criteria provided, single submitter
4796517	NM_001844.5(COL2A1):c.2464-2A>T	COL2A1	Likely pathogenic	criteria provided, single submitter
4796588	NM_001844.5(COL2A1):c.2957C>T (p.Pro986Leu)	COL2A1	Likely pathogenic	criteria provided, single submitter
829805	NM_001844.5(COL2A1):c.3563G>C (p.Gly1188Ala)	COL2A1	Likely pathogenic	criteria provided, single submitter
392663	NM_002860.4(ALDH18A1):c.991A>C (p.Thr331Pro)	ALDH18A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 46 · Orphanet: 23 · 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
COL2A1	Definitive	Autosomal dominant	spondyloepiphyseal dysplasia with metatarsal shortening	46

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita
ALDH18A1	Orphanet:35664	ALDH18A1-related De Barsy syndrome
ALDH18A1	Orphanet:447753	Autosomal dominant spastic paraplegia type 9A
ALDH18A1	Orphanet:447757	Autosomal dominant spastic paraplegia type 9B
ALDH18A1	Orphanet:447760	Autosomal recessive spastic paraplegia type 9B
ALDH18A1	Orphanet:90348	Autosomal dominant cutis laxa

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
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	gencc,clinvar
ALDH18A1	HGNC:9722	ENSG00000059573	P54886	Delta-1-pyrroline-5-carboxylate synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.
ALDH18A1	Delta-1-pyrroline-5-carboxylate synthase	Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
ALDH18A1	Kinase	yes		GPR_dom, Asp/Glu/Uridylate_kinase, Glu/AcGlu_kinase

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
cartilage tissue	1
corpus epididymis	1
tibia	1
ileal mucosa	1
jejunal mucosa	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis
ALDH18A1	263	ubiquitous	marker	parotid gland, jejunal mucosa, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDH18A1	7,351
COL2A1	2,491

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL2A1	P02458	11
ALDH18A1	P54886	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Glutamate and glutamine metabolism	1	407.9×	0.017	ALDH18A1
Fibronectin matrix formation	1	285.5×	0.017	COL2A1
MET activates PTK2 signaling	1	190.3×	0.017	COL2A1
Collagen chain trimerization	1	129.8×	0.017	COL2A1
Signaling by PDGF	1	126.9×	0.017	COL2A1
NCAM1 interactions	1	124.1×	0.017	COL2A1
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.017	COL2A1
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.017	COL2A1
Collagen degradation	1	87.8×	0.017	COL2A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.017	COL2A1
Non-integrin membrane-ECM interactions	1	77.2×	0.017	COL2A1
ECM proteoglycans	1	75.1×	0.017	COL2A1
Integrin cell surface interactions	1	67.2×	0.017	COL2A1
Mitochondrial protein degradation	1	57.1×	0.019	ALDH18A1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	43.6×	0.023	COL2A1

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
L-ornithine biosynthetic process	1	8426.0×	0.003	ALDH18A1
L-citrulline biosynthetic process	1	2106.5×	0.003	ALDH18A1
L-proline biosynthetic process	1	1404.3×	0.003	ALDH18A1
otic vesicle development	1	1404.3×	0.003	COL2A1
anterior head development	1	1404.3×	0.003	COL2A1
cartilage development involved in endochondral bone morphogenesis	1	1203.7×	0.003	COL2A1
proteoglycan metabolic process	1	936.2×	0.003	COL2A1
notochord development	1	842.6×	0.003	COL2A1
response to temperature stimulus	1	766.0×	0.003	ALDH18A1
limb bud formation	1	766.0×	0.003	COL2A1
embryonic skeletal joint morphogenesis	1	766.0×	0.003	COL2A1
glutamate metabolic process	1	561.7×	0.004	ALDH18A1
cartilage condensation	1	383.0×	0.006	COL2A1
tissue homeostasis	1	280.9×	0.007	COL2A1
cellular response to BMP stimulus	1	280.9×	0.007	COL2A1
endochondral ossification	1	271.8×	0.007	COL2A1
extrinsic apoptotic signaling pathway in absence of ligand	1	234.1×	0.007	COL2A1
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	205.5×	0.008	COL2A1
heart morphogenesis	1	187.2×	0.008	COL2A1
chondrocyte differentiation	1	150.5×	0.009	COL2A1
inner ear morphogenesis	1	150.5×	0.009	COL2A1
cartilage development	1	125.8×	0.010	COL2A1
roof of mouth development	1	123.9×	0.010	COL2A1
collagen fibril organization	1	112.3×	0.011	COL2A1
skeletal system development	1	62.9×	0.018	COL2A1
central nervous system development	1	57.7×	0.019	COL2A1
sensory perception of sound	1	50.5×	0.021	COL2A1
regulation of gene expression	1	41.7×	0.025	COL2A1
visual perception	1	39.8×	0.025	COL2A1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL2A1	0	0
ALDH18A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ALDH18A1	3	Binding:3
COL2A1	2	Binding:2

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	1	ALDH18A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COL2A1

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)
COL2A1	2	—
ALDH18A1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.