Spondyloepiphyseal dysplasia with congenital joint dislocations
diseaseOn this page
Also known as bifurcation of distal humerus with oligoectro-syndactylychondrodysplasia with congenital joint dislocations, CHST3 typechondrodysplasia with multiple dislocationsCHST3-related skeletal dysplasiaGollop Coates syndromeHumerospinal dysostosisSDCD, CHST3 typeSEDCJDspondyloepiphyseal dysplasiaspondyloepiphyseal dysplasia with congenital joint dyslocations, CHST3 type
Summary
Spondyloepiphyseal dysplasia with congenital joint dislocations (MONDO:0007738) is a disease caused by CHST3 (GenCC Definitive), with 2 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: CHST3 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 387
- Phenotypes (HPO): 26
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 2 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Signs & symptoms
Clinical features (HPO)
26 HPO clinical features (Orphanet curated; top 26 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000316 | Hypertelorism | Very frequent (80-99%) |
| HP:0001156 | Brachydactyly | Very frequent (80-99%) |
| HP:0001371 | Flexion contracture | Very frequent (80-99%) |
| HP:0001552 | Barrel-shaped chest | Very frequent (80-99%) |
| HP:0002515 | Waddling gait | Very frequent (80-99%) |
| HP:0002650 | Scoliosis | Very frequent (80-99%) |
| HP:0002829 | Arthralgia | Very frequent (80-99%) |
| HP:0002857 | Genu valgum | Very frequent (80-99%) |
| HP:0002945 | Intervertebral space narrowing | Very frequent (80-99%) |
| HP:0002967 | Cubitus valgus | Very frequent (80-99%) |
| HP:0003037 | Enlarged joints | Very frequent (80-99%) |
| HP:0003312 | Abnormal form of the vertebral bodies | Very frequent (80-99%) |
| HP:0003521 | Disproportionate short-trunk short stature | Very frequent (80-99%) |
| HP:0008905 | Rhizomelia | Very frequent (80-99%) |
| HP:0009811 | Abnormality of the elbow | Very frequent (80-99%) |
| HP:0010582 | Irregular epiphyses | Very frequent (80-99%) |
| HP:0010585 | Small epiphyses | Very frequent (80-99%) |
| HP:0045075 | Sparse eyebrow | Very frequent (80-99%) |
| HP:0000337 | Broad forehead | Frequent (30-79%) |
| HP:0000343 | Long philtrum | Frequent (30-79%) |
| HP:0000684 | Delayed eruption of teeth | Frequent (30-79%) |
| HP:0001270 | Motor delay | Frequent (30-79%) |
| HP:0002553 | Highly arched eyebrow | Frequent (30-79%) |
| HP:0002751 | Kyphoscoliosis | Frequent (30-79%) |
| HP:0010049 | Short metacarpal | Frequent (30-79%) |
| HP:0030680 | Abnormal cardiovascular system morphology | Frequent (30-79%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | spondyloepiphyseal dysplasia with congenital joint dislocations |
| Mondo ID | MONDO:0007738 |
| MeSH | C537283 |
| OMIM | 143095 |
| Orphanet | 263463 |
| DOID | DOID:0050813 |
| SNOMED CT | 702400006 |
| UMLS | C1837657 |
| MedGen | 373381 |
| GARD | 0013169 |
| Is cancer (heuristic) | no |
Also known as: bifurcation of distal humerus with oligoectro-syndactyly · chondrodysplasia with congenital joint dislocations, CHST3 type · chondrodysplasia with multiple dislocations · CHST3-related skeletal dysplasia · Gollop Coates syndrome · Humerospinal dysostosis · SDCD, CHST3 type · SEDCJD · spondyloepiphyseal dysplasia · spondyloepiphyseal dysplasia with congenital joint dislocations · spondyloepiphyseal dysplasia with congenital joint dyslocations, CHST3 type
Data availability: 387 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › mineral metabolism disease › spondyloepiphyseal dysplasia with congenital joint dislocations
Related subtypes (12): iron metabolism disease, phosphorus metabolism disease, potassium deficiency disease, calcium metabolic disease, diastrophic dysplasia, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, achondrogenesis type IB, chondrodysplasia with joint dislocations, gPAPP type, spondyloepimetaphyseal dysplasia, PAPSS2 type, acquired mineral metabolism disease, sulfur metabolism disease
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
387 retrieved; paginated sample, class counts are floors:
168 uncertain significance, 134 likely benign, 32 pathogenic, 18 likely pathogenic, 12 benign, 12 conflicting classifications of pathogenicity, 6 benign/likely benign, 5 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1039079 | NM_004273.5(CHST3):c.334G>T (p.Glu112Ter) | CHST3 | Pathogenic | criteria provided, single submitter |
| 1406206 | NM_004273.5(CHST3):c.362dup (p.Glu122fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 1445618 | NM_004273.5(CHST3):c.271C>T (p.Gln91Ter) | CHST3 | Pathogenic | criteria provided, single submitter |
| 1452559 | NM_004273.5(CHST3):c.1150_1166del (p.Glu384fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 1454776 | NM_004273.5(CHST3):c.763del (p.Leu255fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 1458337 | NM_004273.5(CHST3):c.238del (p.Ser79_Leu80insTer) | CHST3 | Pathogenic | criteria provided, single submitter |
| 1474566 | NM_004273.5(CHST3):c.1177del (p.Pro392_Leu393insTer) | CHST3 | Pathogenic | criteria provided, single submitter |
| 1685635 | NM_004273.5(CHST3):c.141-1G>C | CHST3 | Pathogenic | criteria provided, single submitter |
| 1996399 | NM_004273.5(CHST3):c.58_77dup (p.Leu26_Phe27insTer) | CHST3 | Pathogenic | criteria provided, single submitter |
| 2028477 | NM_004273.5(CHST3):c.375_378dup (p.Ala127fs) | CHST3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2083760 | NM_004273.5(CHST3):c.83T>A (p.Leu28Ter) | CHST3 | Pathogenic | criteria provided, single submitter |
| 2087753 | NM_004273.5(CHST3):c.855del (p.Leu286fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 2136893 | NM_004273.5(CHST3):c.661C>T (p.Arg221Cys) | CHST3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 225684 | NM_004273.5(CHST3):c.1063G>A (p.Gly355Arg) | CHST3 | Pathogenic | no assertion criteria provided |
| 2428494 | NM_004273.5(CHST3):c.976dup (p.Asp326fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 3676659 | NM_004273.5(CHST3):c.685_686del (p.Cys229fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 3720938 | NM_004273.5(CHST3):c.718A>T (p.Lys240Ter) | CHST3 | Pathogenic | criteria provided, single submitter |
| 432012 | NM_004273.5(CHST3):c.533dup (p.Ala179fs) | CHST3 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4709735 | NM_004273.5(CHST3):c.802G>T (p.Glu268Ter) | CHST3 | Pathogenic | criteria provided, single submitter |
| 4716158 | NM_004273.5(CHST3):c.696dup (p.Val233fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 4742464 | NM_004273.5(CHST3):c.723dup (p.Phe242fs) | CHST3 | Pathogenic | criteria provided, single submitter |
| 478822 | NM_004273.5(CHST3):c.904G>C (p.Asp302His) | CHST3 | Pathogenic | criteria provided, single submitter |
| 478823 | NM_004273.5(CHST3):c.491C>T (p.Pro164Leu) | CHST3 | Pathogenic | criteria provided, single submitter |
| 522996 | NM_004273.5(CHST3):c.1312C>T (p.Gln438Ter) | CHST3 | Pathogenic | criteria provided, single submitter |
| 6041 | NM_004273.5(CHST3):c.776T>C (p.Leu259Pro) | CHST3 | Pathogenic | no assertion criteria provided |
| 6042 | NM_004273.5(CHST3):c.1114G>A (p.Glu372Lys) | CHST3 | Pathogenic | no assertion criteria provided |
| 6043 | NM_004273.5(CHST3):c.664C>T (p.Arg222Trp) | CHST3 | Pathogenic | no assertion criteria provided |
| 6044 | NM_004273.5(CHST3):c.920T>C (p.Leu307Pro) | CHST3 | Pathogenic | no assertion criteria provided |
| 6045 | NM_004273.5(CHST3):c.1086del (p.Arg363fs) | CHST3 | Pathogenic | no assertion criteria provided |
| 6046 | NM_004273.5(CHST3):c.603C>A (p.Tyr201Ter) | CHST3 | Pathogenic | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 2 · 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 |
|---|---|---|---|---|
| CHST3 | Definitive | Autosomal recessive | spondyloepiphyseal dysplasia with congenital joint dislocations | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CHST3 | Orphanet:263463 | CHST3-related skeletal dysplasia |
| MT-TV | Orphanet:255210 | Mitochondrial DNA-associated Leigh syndrome |
Cohort genes → proteins
2 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CHST3 | HGNC:1971 | ENSG00000122863 | Q7LGC8 | Carbohydrate sulfotransferase 3 | gencc,clinvar |
| MT-TV | HGNC:7500 | ENSG00000210077 | mitochondrially encoded tRNA-Val (GUN) | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CHST3 | Carbohydrate sulfotransferase 3 | Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. |
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 |
|---|---|---|---|
| Enzyme (other) | 1 | 6.0× | 0.320 |
| Other/Unknown | 1 | 0.9× | 0.805 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CHST3 | Enzyme (other) | yes | 2.8.2.17 | Sulfotransferase_dom, Carbohydrate_sulfotransferase, P-loop_NTPase |
| MT-TV | Other/Unknown | no |
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 |
| tibia | 1 |
| ventricular zone | 1 |
| amygdala | 1 |
| prefrontal cortex | 1 |
| sural nerve | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CHST3 | 233 | ubiquitous | marker | tibia, cartilage tissue, ventricular zone |
| MT-TV | 118 | ubiquitous | marker | sural nerve, prefrontal cortex, amygdala |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CHST3 | 579 |
| MT-TV | 0 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 1
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CHST3 | Q7LGC8 | 80.58 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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 |
|---|---|---|---|---|
| Defective CHST3 causes SEDCJD | 1 | 1427.5× | 0.002 | CHST3 |
| CS-GAG biosynthesis | 1 | 543.8× | 0.003 | CHST3 |
| Keratan sulfate biosynthesis | 1 | 380.7× | 0.003 | CHST3 |
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 |
|---|---|---|---|---|
| N-acetylglucosamine metabolic process | 1 | 1203.7× | 0.002 | CHST3 |
| sulfur compound metabolic process | 1 | 1123.5× | 0.002 | CHST3 |
| keratan sulfate proteoglycan biosynthetic process | 1 | 991.3× | 0.002 | CHST3 |
| chondroitin sulfate proteoglycan biosynthetic process | 1 | 624.1× | 0.002 | CHST3 |
| T cell homeostasis | 1 | 455.5× | 0.003 | CHST3 |
| carbohydrate metabolic process | 1 | 135.9× | 0.007 | CHST3 |
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 |
|---|---|---|
| CHST3 | 0 | 0 |
| MT-TV | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| CHST3 | 2.8.2.17 | chondroitin 6-sulfotransferase |
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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 1 | CHST3 |
| E | Difficult family or no structure, no drug | 1 | MT-TV |
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) |
|---|---|---|
| CHST3 | 0 | — |
| MT-TV | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.