Ehlers-Danlos syndrome, spondylodysplastic type, 1

Summary

Ehlers-Danlos syndrome, spondylodysplastic type, 1 (MONDO:0020682) is a disease caused by B4GALT7 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: B4GALT7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, spondylodysplastic type, 1
Mondo ID	MONDO:0020682
OMIM	130070
DOID	DOID:0080738
UMLS	C4552003
MedGen	1646889
GARD	0025209
Is cancer (heuristic)	no

Also known as: dermatan sulfate proteoglycan · dermatan sulphate proteoglycan · EDSSPD1 · Ehlers-Danlos syndrome with Short stature and Limb anomalies · Ehlers-Danlos syndrome, progeroid type 1 · Ehlers-Danlos syndrome, progeroid type, 1 · Ehlers-Danlos syndrome, spondylodysplastic type, 1 · galactosyltransferase 1 deficiency · PDS, defective biosynthesis of · proteodermatan sulfate, defective biosynthesis of · XGPT deficiency · xylosylprotein 4-Beta-galactosyltransferase deficiency

Data availability: 20 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › Ehlers-Danlos syndrome, spondylodysplastic type › Ehlers-Danlos syndrome, spondylodysplastic type, 1

Related subtypes (2): Ehlers-Danlos syndrome, spondylocheirodysplastic type, Ehlers-Danlos syndrome, spondylodysplastic 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

20 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 4 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 not provided, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
253108	NM_007255.3(B4GALT7):c.421C>T (p.Arg141Trp)	B4GALT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253109	NM_007255.3(B4GALT7):c.277dup (p.His93fs)	B4GALT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5613	NM_007255.3(B4GALT7):c.808C>T (p.Arg270Cys)	B4GALT7	Pathogenic	criteria provided, multiple submitters, no conflicts
197288	NM_007255.3(B4GALT7):c.687C>T (p.Asp229=)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
253110	NM_007255.3(B4GALT7):c.641G>A (p.Cys214Tyr)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282261	NM_007255.3(B4GALT7):c.38G>A (p.Trp13Ter)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
632558	NM_007255.3(B4GALT7):c.398A>G (p.Gln133Arg)	B4GALT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1361602	NM_007255.3(B4GALT7):c.337C>T (p.Pro113Ser)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1394504	NM_007255.3(B4GALT7):c.639+5G>A	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1417330	NM_007255.3(B4GALT7):c.272_273delinsTT (p.Gly91Val)	B4GALT7	Uncertain significance	criteria provided, single submitter
1438619	NM_007255.3(B4GALT7):c.737C>T (p.Ser246Leu)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1446770	NM_007255.3(B4GALT7):c.620C>T (p.Ser207Phe)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679331	NM_007255.3(B4GALT7):c.685G>A (p.Asp229Asn)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1921914	NM_007255.3(B4GALT7):c.239C>T (p.Pro80Leu)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439463	NM_007255.3(B4GALT7):c.188G>T (p.Gly63Val)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441874	NM_007255.3(B4GALT7):c.667G>A (p.Gly223Ser)	B4GALT7	Uncertain significance	criteria provided, single submitter
2687897	NM_007255.3(B4GALT7):c.640-12T>A	B4GALT7	Uncertain significance	criteria provided, single submitter
284046	NM_007255.3(B4GALT7):c.791G>A (p.Arg264Gln)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
429672	NM_007255.3(B4GALT7):c.313T>G (p.Phe105Val)	B4GALT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
4279953	NM_007255.3(B4GALT7):c.882_883insTTGAGGTGGATTAAACCAAACCCAGCTACGCAAAATCTTAG (p.Ala295fs)	B4GALT7	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
B4GALT7	Definitive	Autosomal recessive	Ehlers-Danlos syndrome, spondylodysplastic type, 1	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
B4GALT7	Orphanet:75496	B4GALT7-related spondylodysplastic 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
B4GALT7	HGNC:930	ENSG00000027847	Q9UBV7	Beta-1,4-galactosyltransferase 7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
B4GALT7	Beta-1,4-galactosyltransferase 7	Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts.

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)
B4GALT7	Enzyme (other)	yes	2.4.1.133	Galactosyl_T, Galactosyl_T_C, Galactosyl_T_N

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
left adrenal gland	1
right adrenal gland	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
B4GALT7	259	ubiquitous	marker	tendon of biceps brachii, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
B4GALT7	1,645

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
B4GALT7	Q9UBV7	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Chondroitin sulfate/dermatan sulfate metabolism	1	951.7×	0.005	B4GALT7
Diseases associated with glycosaminoglycan metabolism	1	761.3×	0.005	B4GALT7
Defective B4GALT7 causes EDS, progeroid type	1	571.0×	0.005	B4GALT7
Heparan sulfate/heparin (HS-GAG) metabolism	1	543.8×	0.005	B4GALT7
Glycosaminoglycan-protein linkage region biosynthesis	1	393.8×	0.006	B4GALT7
Glycosaminoglycan metabolism	1	219.6×	0.008	B4GALT7
Diseases of glycosylation	1	131.3×	0.011	B4GALT7
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.011	B4GALT7
Diseases of metabolism	1	80.4×	0.015	B4GALT7
Disease	1	13.1×	0.084	B4GALT7
Metabolism	1	11.6×	0.086	B4GALT7

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
glycosaminoglycan-protein linkage region biosynthetic process	1	4213.0×	0.002	B4GALT7
proteoglycan metabolic process	1	1872.4×	0.002	B4GALT7
supramolecular fiber organization	1	1053.2×	0.002	B4GALT7
glycosaminoglycan biosynthetic process	1	842.6×	0.002	B4GALT7
proteoglycan biosynthetic process	1	842.6×	0.002	B4GALT7
negative regulation of fibroblast proliferation	1	495.6×	0.003	B4GALT7
protein N-linked glycosylation	1	263.3×	0.005	B4GALT7
protein modification process	1	244.2×	0.005	B4GALT7
carbohydrate metabolic process	1	135.9×	0.007	B4GALT7

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
B4GALT7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
B4GALT7	2.4.1.133, 2.4.1.38	xylosylprotein 4-beta-galactosyltransferase, beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase

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	1	B4GALT7
D	Druggable family + AlphaFold only, no drug	0
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)
B4GALT7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.