Spondylo-ocular syndrome

Summary

Spondylo-ocular syndrome (MONDO:0011604) is a disease caused by XYLT2 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: XYLT2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19
• Phenotypes (HPO): 31

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000534	Abnormal eyebrow morphology	Very frequent (80-99%)
HP:0000541	Retinal detachment	Very frequent (80-99%)
HP:0000572	Visual loss	Very frequent (80-99%)
HP:0000926	Platyspondyly	Very frequent (80-99%)
HP:0000939	Osteoporosis	Very frequent (80-99%)
HP:0002942	Thoracic kyphosis	Very frequent (80-99%)
HP:0003521	Disproportionate short-trunk short stature	Very frequent (80-99%)
HP:0005108	Abnormal intervertebral disk morphology	Very frequent (80-99%)
HP:0007730	Iris hypopigmentation	Very frequent (80-99%)
HP:0000297	Facial hypotonia	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000568	Microphthalmia	Frequent (30-79%)
HP:0001629	Ventricular septal defect	Frequent (30-79%)
HP:0001763	Pes planus	Frequent (30-79%)
HP:0008063	Aplasia/Hypoplasia of the lens	Frequent (30-79%)
HP:0000233	Thin vermilion border	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000391	Thickened helices	Occasional (5-29%)
HP:0000465	Webbed neck	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000974	Hyperextensible skin	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0002162	Low posterior hairline	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0004467	Preauricular pit	Occasional (5-29%)
HP:0009738	Abnormality of the antihelix	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spondylo-ocular syndrome
Mondo ID	MONDO:0011604
OMIM	605822
Orphanet	85194
ICD-11	1611450426
SNOMED CT	715653007
UMLS	C4225412
MedGen	900371
GARD	0016740
Is cancer (heuristic)	no

Also known as: SOS · spondyloocular syndrome

Data availability: 19 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital vitreoretinal dysplasia › spondylo-ocular syndrome

Related subtypes (8): osteoporosis-pseudoglioma syndrome, Coats disease, incontinentia pigmenti, Norrie disease, Coats plus syndrome, trisomy 13, retinal capillary malformation, persistent hyperplastic primary vitreous

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

19 retrieved; paginated sample, class counts are floors:

8 benign, 4 uncertain significance, 4 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
207977	NM_022167.4(XYLT2):c.692dup (p.Val232fs)	XYLT2	Pathogenic	criteria provided, multiple submitters, no conflicts
207978	NM_022167.4(XYLT2):c.520del (p.Ala174fs)	XYLT2	Pathogenic	no assertion criteria provided
2570659	NM_022167.4(XYLT2):c.1584del (p.Gly529fs)	XYLT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3340122	NM_022167.4(XYLT2):c.1736del (p.Pro579fs)	XYLT2	Likely pathogenic	criteria provided, single submitter
548446	NM_022167.4(XYLT2):c.2548G>A (p.Asp850Asn)	XYLT2	Likely pathogenic	no assertion criteria provided
804420	NM_022167.4(XYLT2):c.1584dup (p.Gly529fs)	XYLT2	Likely pathogenic	criteria provided, single submitter
974777	NM_022167.4(XYLT2):c.1552del (p.Leu518fs)	XYLT2	Likely pathogenic	criteria provided, single submitter
1030800	NM_022167.4(XYLT2):c.749G>A (p.Arg250His)	XYLT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1372865	NM_022167.4(XYLT2):c.1582C>T (p.Pro528Ser)	XYLT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1921989	NM_022167.4(XYLT2):c.1924C>T (p.Arg642Trp)	XYLT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064120	NM_022167.4(XYLT2):c.2443G>T (p.Glu815Ter)	XYLT2	Uncertain significance	criteria provided, single submitter
1227335	NM_022167.4(XYLT2):c.1569T>C (p.Tyr523=)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts
1243238	NM_022167.4(XYLT2):c.177G>A (p.Glu59=)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts
1274419	NM_022167.4(XYLT2):c.342C>T (p.Pro114=)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts
1277109	NM_022167.4(XYLT2):c.30G>T (p.Leu10=)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts
1279201	NM_022167.4(XYLT2):c.1938G>A (p.Leu646=)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts
1289379	NM_022167.4(XYLT2):c.914G>C (p.Arg305Thr)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts
2533	NM_022167.4(XYLT2):c.2402C>G (p.Thr801Arg)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts
709151	NM_022167.4(XYLT2):c.922C>T (p.Leu308=)	XYLT2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
XYLT2	Strong	Autosomal recessive	spondylo-ocular syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XYLT2	Orphanet:85194	Spondylo-ocular 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
XYLT2	HGNC:15517	ENSG00000015532	Q9H1B5	Xylosyltransferase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XYLT2	Xylosyltransferase 2	Catalyzes the first step in the biosynthesis of chondroitin sulfate, heparan sulfate and dermatan sulfate proteoglycans, such as DCN.

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)
XYLT2	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT

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
body of stomach	1
fundus of stomach	1
stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XYLT2	237	ubiquitous	marker	body of stomach, stomach, fundus of stomach

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XYLT2	850

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
XYLT2	Q9H1B5	84.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Glycosaminoglycan-protein linkage region biosynthesis	1	393.8×	0.003	XYLT2

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×	9e-04	XYLT2
glycosaminoglycan biosynthetic process	1	842.6×	0.002	XYLT2
chondroitin sulfate proteoglycan biosynthetic process	1	624.1×	0.002	XYLT2
heparan sulfate proteoglycan biosynthetic process	1	561.7×	0.002	XYLT2

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
XYLT2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
XYLT2	2.4.2.26	protein xylosyltransferase

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	XYLT2
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)
XYLT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.