Craniosynostosis with ectopia lentis

Summary

Craniosynostosis with ectopia lentis (MONDO:0011347) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	craniosynostosis with ectopia lentis
Mondo ID	MONDO:0011347
MeSH	C566357
OMIM	603595
UMLS	C1863678
MedGen	350949
GARD	0024790
Is cancer (heuristic)	no

Also known as: craniosynostosis with ectopia lentis

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › dysostosis › synostosis › craniosynostosis › craniosynostosis with ectopia lentis

Related subtypes (28): craniosynostosis, Adelaide type, craniosynostosis syndrome, autosomal recessive, craniosynostosis with ocular abnormalities and hallucal defects, isolated craniosynostosis, syndromic craniosynostosis, craniosynostosis Fontaine type, craniosynostosis Maroteaux Fonfria type, craniosynostosis alopecia brain defect, craniosynostosis arthrogryposis cleft palate, craniosynostosis autosomal dominant, craniosynostosis cleft lip palate arthrogryposis, craniosynostosis contractures cleft, craniosynostosis exostoses nevus epibulbar dermoid, craniosynostosis intellectual disability heart defects, Hordnes Engebretsen Knudtson syndrome, Iida Kannari syndrome, mehta lewis patton syndrome, non-syndromic unicoronal craniosynostosis, non-syndromic unilambdoid craniosynostosis, non-syndromic unifrontosphenoidal craniosynostosis, non-syndromic unisquamosal craniosynostosis, non-syndromic multisutural craniosynostosis, non-syndromic non-specific multisutural craniosynostosis, non-syndromic bilambdoid craniosynostosis, non-syndromic unicoronal and sagittal craniosynostosis, non-syndromic metopic and sagittal craniosynostosis, non-syndromic bicoronal and metopic craniosynostosis, non-syndromic bicoronal and sagittal craniosynostosis

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

4 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323859	NM_019032.6(ADAMTSL4):c.2270del (p.Gly757fs)	ADAMTSL4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39555	NM_019032.6(ADAMTSL4):c.767_786del (p.Gln256fs)	ADAMTSL4	Pathogenic	criteria provided, multiple submitters, no conflicts
1325408	NM_019032.6(ADAMTSL4):c.2177+3_2177+6del	ADAMTSL4	Likely pathogenic	criteria provided, single submitter
3254634	NM_019032.6(ADAMTSL4):c.2178-2A>T	ADAMTSL4	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAMTSL4	Orphanet:1885	Isolated ectopia lentis

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
ADAMTSL4	HGNC:19706	ENSG00000143382	Q6UY14	ADAMTS-like protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADAMTSL4	ADAMTS-like protein 4	Positive regulation of apoptosis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAMTSL4	Other/Unknown	no		TSP1_rpt, ADAMTS_spacer1, PLAC

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
decidua	1
lower esophagus mucosa	1
mucosa of stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAMTSL4	216	ubiquitous	marker	decidua, mucosa of stomach, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAMTSL4	1,231

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAMTSL4	Q6UY14	65.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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 B3GALTL causes PpS	1	308.6×	0.014	ADAMTSL4
O-glycosylation of TSR domain-containing proteins	1	300.5×	0.014	ADAMTSL4
Diseases associated with O-glycosylation of proteins	1	215.5×	0.014	ADAMTSL4
O-linked glycosylation	1	144.6×	0.014	ADAMTSL4
Diseases of glycosylation	1	131.3×	0.014	ADAMTSL4
Diseases of metabolism	1	80.4×	0.019	ADAMTSL4
Post-translational protein modification	1	19.2×	0.067	ADAMTSL4
Disease	1	13.1×	0.081	ADAMTSL4
Metabolism of proteins	1	12.4×	0.081	ADAMTSL4

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
pigment cell development	1	16852.0×	3e-04	ADAMTSL4
epithelial cell development	1	1532.0×	0.002	ADAMTSL4
extracellular matrix organization	1	122.1×	0.014	ADAMTSL4
positive regulation of apoptotic process	1	56.7×	0.022	ADAMTSL4
apoptotic process	1	28.7×	0.035	ADAMTSL4

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
ADAMTSL4	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	1	ADAMTSL4

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)
ADAMTSL4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.