Ehlers-Danlos syndrome, spondylocheirodysplastic type

Summary

Ehlers-Danlos syndrome, spondylocheirodysplastic type (MONDO:0012873) is a disease caused by SLC39A13 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC39A13 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 305
• Phenotypes (HPO): 20

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0000520	Proptosis	Very frequent (80-99%)
HP:0000592	Blue sclerae	Very frequent (80-99%)
HP:0000963	Thin skin	Very frequent (80-99%)
HP:0000974	Hyperextensible skin	Very frequent (80-99%)
HP:0000978	Bruising susceptibility	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0002652	Skeletal dysplasia	Very frequent (80-99%)
HP:0008848	Moderately short stature	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000926	Platyspondyly	Frequent (30-79%)
HP:0000938	Osteopenia	Frequent (30-79%)
HP:0000944	Abnormal metaphysis morphology	Frequent (30-79%)
HP:0001182	Tapered finger	Frequent (30-79%)
HP:0003071	Flattened epiphysis	Frequent (30-79%)
HP:0003370	Flat capital femoral epiphysis	Frequent (30-79%)
HP:0003393	Thenar muscle atrophy	Frequent (30-79%)
HP:0006429	Broad femoral neck	Frequent (30-79%)
HP:0010489	Absent palmar crease	Frequent (30-79%)
HP:0100864	Short femoral neck	Frequent (30-79%)
HP:0001371	Flexion contracture	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, spondylocheirodysplastic type
Mondo ID	MONDO:0012873
MeSH	C567340
OMIM	612350
Orphanet	157965
DOID	DOID:0080739
ICD-11	1653521697
UMLS	C2676510
MedGen	393515
GARD	0012610
Is cancer (heuristic)	no

Also known as: EDS, spondylocheirodysplastic type · EDSSPD3

Data availability: 305 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, spondylocheirodysplastic type

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

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

305 retrieved; paginated sample, class counts are floors:

176 likely benign, 92 uncertain significance, 21 conflicting classifications of pathogenicity, 8 benign, 7 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2132	NM_001128225.3(SLC39A13):c.483_491del (p.Phe162_Ala164del)	SLC39A13	Pathogenic	criteria provided, single submitter
1129163	NM_001128225.3(SLC39A13):c.934G>A (p.Ala312Thr)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1371385	NM_001128225.3(SLC39A13):c.1043G>A (p.Arg348His)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1424130	NM_001128225.3(SLC39A13):c.112C>T (p.Arg38Trp)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1556567	NM_001128225.3(SLC39A13):c.786+7G>C	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1589329	NM_001128225.3(SLC39A13):c.919+14G>A	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195411	NM_001128225.3(SLC39A13):c.222T>A (p.Gly74=)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196579	NM_001128225.3(SLC39A13):c.398C>T (p.Thr133Met)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198279	NM_001128225.3(SLC39A13):c.646-7T>C	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
199188	NM_001128225.3(SLC39A13):c.978C>T (p.Gly326=)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2133	NM_001128225.3(SLC39A13):c.221G>A (p.Gly74Asp)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
284085	NM_001128225.3(SLC39A13):c.786+6C>T	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287155	NM_001128225.3(SLC39A13):c.439C>G (p.Gln147Glu)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288218	NM_001128225.3(SLC39A13):c.132G>A (p.Thr44=)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
383728	NM_001128225.3(SLC39A13):c.1037C>T (p.Pro346Leu)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
391481	NM_001128225.3(SLC39A13):c.571G>A (p.Ala191Thr)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
392333	NM_001128225.3(SLC39A13):c.1090G>T (p.Val364Leu)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
506982	NM_001128225.3(SLC39A13):c.786+8C>T	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
508857	NM_001128225.3(SLC39A13):c.888C>T (p.Phe296=)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
511056	NM_001128225.3(SLC39A13):c.621C>T (p.Leu207=)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
651607	NM_001128225.3(SLC39A13):c.118C>T (p.Arg40Trp)	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
653236	NM_001128225.3(SLC39A13):c.302-3T>C	SLC39A13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1008557	NM_001128225.3(SLC39A13):c.191G>A (p.Arg64Gln)	SLC39A13	Uncertain significance	criteria provided, single submitter
1010781	NM_001128225.3(SLC39A13):c.38G>T (p.Gly13Val)	SLC39A13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1019768	NM_001128225.3(SLC39A13):c.113G>A (p.Arg38Gln)	SLC39A13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1023087	NM_001128225.3(SLC39A13):c.589T>C (p.Cys197Arg)	SLC39A13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1064330	NM_001128225.3(SLC39A13):c.392C>T (p.Ala131Val)	SLC39A13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1163521	NM_001128225.3(SLC39A13):c.140G>A (p.Arg47His)	SLC39A13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1196182	NM_001128225.3(SLC39A13):c.889G>A (p.Ala297Thr)	SLC39A13	Uncertain significance	criteria provided, multiple submitters, no conflicts
1200994	NM_001128225.3(SLC39A13):c.355G>T (p.Gly119Cys)	SLC39A13	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
SLC39A13	Definitive	Autosomal recessive	Ehlers-Danlos syndrome, spondylocheirodysplastic type	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC39A13	Orphanet:157965	SLC39A13-related spondylodysplastic Ehlers-Danlos 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
SLC39A13	HGNC:20859	ENSG00000165915	Q96H72	Zinc transporter ZIP13	gencc,clinvar
SLC39A13-AS1	HGNC:56351	ENSG00000255197		SLC39A13 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC39A13	Zinc transporter ZIP13	Functions as a zinc transporter transporting Zn(2+) from the Golgi apparatus to the cytosol and thus influences the zinc level at least in areas of the cytosol.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC39A13	Other/Unknown	no		ZIP
SLC39A13-AS1	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
ascending aorta	1
metanephros cortex	1
thoracic aorta	1
blood	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC39A13	248	ubiquitous	marker	metanephros cortex, ascending aorta, thoracic aorta
SLC39A13-AS1	133		marker	monocyte, leukocyte, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC39A13	1,093
SLC39A13-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC39A13	Q96H72	76.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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
connective tissue development	1	4213.0×	0.001	SLC39A13
zinc ion transport	1	1532.0×	0.002	SLC39A13
zinc ion transmembrane transport	1	702.2×	0.002	SLC39A13
intracellular zinc ion homeostasis	1	481.5×	0.002	SLC39A13
brown fat cell differentiation	1	432.1×	0.002	SLC39A13

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
SLC39A13	0	0
SLC39A13-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	2	SLC39A13, SLC39A13-AS1

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)
SLC39A13	0	—
SLC39A13-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.