spondyloepimetaphyseal dysplasia, Maroteaux type

Summary

spondyloepimetaphyseal dysplasia, Maroteaux type (MONDO:0008473) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	spondyloepimetaphyseal dysplasia, Maroteaux type
Mondo ID	MONDO:0008473
OMIM	184095
Orphanet	263482
DOID	DOID:0111553
SNOMED CT	719204007
UMLS	C3159322
MedGen	463613
GARD	0000994
Is cancer (heuristic)	no

Also known as: brachyolmia Maroteaux type · pseudo-Morquio syndrome type 2 · SED, Maroteaux type · spondyloepimetaphyseal dysplasia, Maroteaux type · spondyloepiphyseal dysplasia Maroteaux type · spondyloepiphyseal dysplasia, Maroteaux type

Data availability: 22 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › TRPV4-related bone disorder › spondyloepimetaphyseal dysplasia, Maroteaux type

Related subtypes (5): autosomal dominant brachyolmia, metatropic dysplasia, parastremmatic dwarfism, spondylometaphyseal dysplasia, Kozlowski type, familial digital arthropathy-brachydactyly

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

22 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 4 pathogenic, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
126478	NM_021625.5(TRPV4):c.2396_2412del (p.Pro799fs)	TRPV4	Pathogenic	no assertion criteria provided
18435	NM_021625.5(TRPV4):c.2389G>A (p.Glu797Lys)	TRPV4	Pathogenic	criteria provided, multiple submitters, no conflicts
30468	NM_021625.5(TRPV4):c.1805A>G (p.Tyr602Cys)	TRPV4	Pathogenic	no assertion criteria provided
4998	NM_021625.5(TRPV4):c.2396C>T (p.Pro799Leu)	TRPV4	Pathogenic	criteria provided, multiple submitters, no conflicts
5000	NM_021625.5(TRPV4):c.806G>A (p.Arg269His)	TRPV4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18437	NM_021625.5(TRPV4):c.547G>A (p.Glu183Lys)	TRPV4	Likely pathogenic	criteria provided, single submitter
234711	NM_021625.5(TRPV4):c.704A>G (p.Tyr235Cys)	TRPV4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
409288	NM_021625.5(TRPV4):c.1976C>T (p.Ser659Leu)	TRPV4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
521109	NM_021625.5(TRPV4):c.1376T>G (p.Leu459Arg)	TRPV4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1024231	NM_021625.5(TRPV4):c.1469A>G (p.Tyr490Cys)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1064181	NM_021625.5(TRPV4):c.190C>T (p.Arg64Ter)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1782619	NM_021625.5(TRPV4):c.1919C>T (p.Ala640Val)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
246569	NM_021625.5(TRPV4):c.2471C>T (p.Ser824Leu)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
2889059	NM_021625.5(TRPV4):c.2321G>A (p.Arg774His)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
3574248	NM_021625.5(TRPV4):c.1667A>C (p.Tyr556Ser)	TRPV4	Uncertain significance	criteria provided, single submitter
3892736	NM_021625.5(TRPV4):c.658A>G (p.Thr220Ala)	TRPV4	Uncertain significance	criteria provided, single submitter
424209	NM_021625.5(TRPV4):c.569C>T (p.Thr190Met)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
448709	NM_021625.5(TRPV4):c.2425G>A (p.Gly809Ser)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
575960	NM_021625.5(TRPV4):c.184G>A (p.Asp62Asn)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
651174	NM_021625.5(TRPV4):c.202C>T (p.Arg68Cys)	TRPV4	Uncertain significance	criteria provided, multiple submitters, no conflicts
137724	NM_021625.5(TRPV4):c.1153-10C>T	TRPV4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
307136	NM_021625.5(TRPV4):c.854-5C>T	TRPV4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPV4	Orphanet:1216	Autosomal dominant congenital benign spinal muscular atrophy
TRPV4	Orphanet:263482	Spondyloepimetaphyseal dysplasia, Maroteaux type
TRPV4	Orphanet:2635	Metatropic dysplasia
TRPV4	Orphanet:431255	Scapuloperoneal spinal muscular atrophy
TRPV4	Orphanet:85169	Familial digital arthropathy-brachydactyly
TRPV4	Orphanet:86820	Familial avascular necrosis of femoral head
TRPV4	Orphanet:93304	Autosomal dominant brachyolmia
TRPV4	Orphanet:93314	Spondylometaphyseal dysplasia, Kozlowski type
TRPV4	Orphanet:99937	Autosomal dominant Charcot-Marie-Tooth disease type 2C

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
TRPV4	HGNC:18083	ENSG00000111199	Q9HBA0	Transient receptor potential cation channel subfamily V member 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV4	Transient receptor potential cation channel subfamily V member 4	Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity.

Protein-family classification

Druggable: 1 · 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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV4	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TrpV1-4

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
lower esophagus mucosa	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV4	171	ubiquitous	marker	cartilage tissue, lower esophagus mucosa, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPV4	1,948

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRPV4	Q9HBA0	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
TRP channels	1	407.9×	0.005	TRPV4
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	160.8×	0.006	TRPV4

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
hyperosmotic salinity response	1	16852.0×	9e-04	TRPV4
blood vessel endothelial cell delamination	1	16852.0×	9e-04	TRPV4
vasopressin secretion	1	8426.0×	9e-04	TRPV4
positive regulation of striated muscle contraction	1	8426.0×	9e-04	TRPV4
regulation of response to osmotic stress	1	8426.0×	9e-04	TRPV4
calcium ion import into cytosol	1	8426.0×	9e-04	TRPV4
cellular hypotonic salinity response	1	5617.3×	0.001	TRPV4
positive regulation of macrophage inflammatory protein 1 alpha production	1	5617.3×	0.001	TRPV4
positive regulation of microtubule depolymerization	1	3370.4×	0.001	TRPV4
positive regulation of chemokine (C-C motif) ligand 5 production	1	2808.7×	0.001	TRPV4
negative regulation of brown fat cell differentiation	1	2808.7×	0.001	TRPV4
positive regulation of chemokine (C-X-C motif) ligand 1 production	1	2808.7×	0.001	TRPV4
cartilage development involved in endochondral bone morphogenesis	1	2407.4×	0.001	TRPV4
regulation of aerobic respiration	1	2106.5×	0.002	TRPV4
cortical microtubule organization	1	1872.4×	0.002	TRPV4
multicellular organismal-level water homeostasis	1	1685.2×	0.002	TRPV4
osmosensory signaling pathway	1	1532.0×	0.002	TRPV4
diet induced thermogenesis	1	1404.3×	0.002	TRPV4
cellular hypotonic response	1	1404.3×	0.002	TRPV4
positive regulation of vascular permeability	1	1296.3×	0.002	TRPV4
cellular response to osmotic stress	1	1203.7×	0.002	TRPV4
positive regulation of monocyte chemotactic protein-1 production	1	1203.7×	0.002	TRPV4
microtubule polymerization	1	887.0×	0.002	TRPV4
positive regulation of macrophage chemotaxis	1	802.5×	0.002	TRPV4
calcium ion import	1	802.5×	0.002	TRPV4
cell volume homeostasis	1	601.9×	0.003	TRPV4
calcium ion import across plasma membrane	1	543.6×	0.003	TRPV4
cell-cell junction assembly	1	443.5×	0.004	TRPV4
cellular response to heat	1	343.9×	0.005	TRPV4
response to mechanical stimulus	1	300.9×	0.005	TRPV4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
TRPV4	6	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANNABINOL	3	TRPV4
TETRAHYDROCANNABIVARIN	2	TRPV4
CANNABIDIVARIN	2	TRPV4
GSK2798745	2	TRPV4
CANNABIGEROL	2	TRPV4
ABT-102	1	TRPV4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TRPV4	99	Binding:94, Functional:5

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

6 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)
CANNABINOL	3	TRPV4
TETRAHYDROCANNABIVARIN	2	TRPV4
CANNABIDIVARIN	2	TRPV4
GSK2798745	2	TRPV4
CANNABIGEROL	2	TRPV4
ABT-102	1	TRPV4

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	1	TRPV4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.