Ehlers-Danlos syndrome, musculocontractural type 1

Summary

Ehlers-Danlos syndrome, musculocontractural type 1 (MONDO:0020681) is a disease caused by CHST14 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CHST14 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, musculocontractural type 1
Mondo ID	MONDO:0020681
OMIM	601776
DOID	DOID:0080736
NCIT	C168975
GARD	0025208
Is cancer (heuristic)	no

Also known as: EDSMC · EDSMC1

Data availability: 26 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › Ehlers-Danlos syndrome, musculocontractural type › Ehlers-Danlos syndrome, musculocontractural type 1

Related subtypes (1): Ehlers-Danlos syndrome, musculocontractural type 2

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

26 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 9 pathogenic, 4 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
446172	NM_130468.3(CHST14):c.[403C>G;410T>A]		Pathogenic	no assertion criteria provided
1705283	NM_130468.4(CHST14):c.711T>A (p.Tyr237Ter)	CHST14	Pathogenic	criteria provided, single submitter
18421	NM_130468.4(CHST14):c.981_1000dup (p.Glu334fs)	CHST14	Pathogenic	no assertion criteria provided
2339	NM_130468.4(CHST14):c.878A>G (p.Tyr293Cys)	CHST14	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2340	NM_130468.4(CHST14):c.842C>T (p.Pro281Leu)	CHST14	Pathogenic	criteria provided, single submitter
2341	NM_130468.4(CHST14):c.205A>T (p.Lys69Ter)	CHST14	Pathogenic	no assertion criteria provided
2342	NM_130468.4(CHST14):c.866G>C (p.Cys289Ser)	CHST14	Pathogenic	no assertion criteria provided
2506367	NM_130468.4(CHST14):c.922C>T (p.Gln308Ter)	CHST14	Pathogenic	criteria provided, single submitter
434766	NM_130468.4(CHST14):c.784G>A (p.Glu262Lys)	CHST14	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
446173	NM_130468.4(CHST14):c.453dup (p.Cys152fs)	CHST14	Pathogenic	no assertion criteria provided
50992	NM_130468.4(CHST14):c.821G>C (p.Arg274Pro)	CHST14	Pathogenic	no assertion criteria provided
2337	NM_130468.4(CHST14):c.638G>C (p.Arg213Pro)	CHST14	Likely pathogenic	criteria provided, single submitter
3900616	NM_130468.4(CHST14):c.870_871delinsT (p.Val291fs)	CHST14	Likely pathogenic	criteria provided, single submitter
4292286	NM_130468.4(CHST14):c.626T>C (p.Phe209Ser)	CHST14	Likely pathogenic	criteria provided, single submitter
4293813	NM_130468.4(CHST14):c.85_95dup (p.Leu34fs)	CHST14	Likely pathogenic	criteria provided, single submitter
2336	NM_130468.4(CHST14):c.145del (p.Ala48_Val49insTer)	CHST14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
772547	NM_130468.4(CHST14):c.315G>A (p.Arg105=)	CHST14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028547	NM_130468.4(CHST14):c.637C>T (p.Arg213Trp)	CHST14	Uncertain significance	criteria provided, single submitter
1032377	NM_130468.4(CHST14):c.61G>A (p.Ala21Thr)	CHST14	Uncertain significance	criteria provided, single submitter
1042108	NM_130468.4(CHST14):c.295G>A (p.Asp99Asn)	CHST14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1445824	NM_130468.4(CHST14):c.933G>C (p.Glu311Asp)	CHST14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1470416	NM_130468.4(CHST14):c.20C>A (p.Thr7Asn)	CHST14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431836	NM_130468.4(CHST14):c.654_655delinsTT (p.Leu219Phe)	CHST14	Uncertain significance	criteria provided, single submitter
2444086	NM_130468.4(CHST14):c.1033dup (p.Arg345fs)	CHST14	Uncertain significance	criteria provided, single submitter
3901900	NM_130468.4(CHST14):c.777dup (p.Phe260fs)	CHST14	Uncertain significance	criteria provided, single submitter
4819304	NM_130468.4(CHST14):c.419A>C (p.His140Pro)	CHST14	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
CHST14	Definitive	Autosomal recessive	Ehlers-Danlos syndrome, musculocontractural type 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHST14	Orphanet:2953	Musculocontractural Ehlers-Danlos syndrome

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
CHST14	HGNC:24464	ENSG00000169105	Q8NCH0	Carbohydrate sulfotransferase 14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHST14	Carbohydrate sulfotransferase 14	Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of dermatan sulfate.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CHST14	Enzyme (other)	yes	2.8.2.35	Sulfotransferase, Carb_sulfotrans_8-10

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
ileal mucosa	1
stromal cell of endometrium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHST14	201	ubiquitous	marker	stromal cell of endometrium, ventricular zone, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHST14	837

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CHST14	Q8NCH0	84.17

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
Defective CHST14 causes EDS, musculocontractural type	1	1427.5×	0.001	CHST14
DS-GAG biosynthesis	1	951.7×	0.001	CHST14

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
dermatan sulfate proteoglycan metabolic process	1	5617.3×	5e-04	CHST14
dermatan sulfate proteoglycan biosynthetic process	1	1685.2×	7e-04	CHST14
carbohydrate biosynthetic process	1	1532.0×	7e-04	CHST14

Therapeutics

Drug target analysis

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

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
CHST14	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CHST14	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHST14	2.8.2.35	dermatan 4-sulfotransferase

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

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	CHST14
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CHST14	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.