Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome

Summary

Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome (MONDO:0011106) is a disease caused by ASPH (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ASPH (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome
Mondo ID	MONDO:0011106
MeSH	C563293
OMIM	601552
Orphanet	412022
UMLS	C1832167
MedGen	330396
GARD	0017688
Is cancer (heuristic)	no

Also known as: facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs · facial dysmorphism-lens dislocation-anterior segment abnormalities-nontraumatic conjunctive cysts syndrome · facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome · FDLAB · FDLAB syndrome · Traboulsi syndrome

Data availability: 34 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › lens disorder › facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome

Related subtypes (9): lens subluxation, posterior dislocation of lens, cataract, blepharoptosis-myopia-ectopia lentis syndrome, classic homocystinuria, congenital primary aphakia, ectopia lentis-chorioretinal dystrophy-myopia syndrome, isolated ectopia lentis, encephalopathy due to sulfite oxidase deficiency

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

34 retrieved; paginated sample, class counts are floors:

11 benign, 7 pathogenic, 7 likely pathogenic, 6 uncertain significance, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184504	NM_004318.4(ASPH):c.2127-2del	ASPH	Pathogenic/Likely pathogenic	no assertion criteria provided
1184505	NM_004318.4(ASPH):c.1695C>A (p.Tyr565Ter)	ASPH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184947	NM_004318.4(ASPH):c.2181_2183dup (p.Trp728Ter)	ASPH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210220	NM_004318.4(ASPH):c.1782G>A (p.Trp594Ter)	ASPH	Pathogenic	criteria provided, single submitter
137614	NM_004318.4(ASPH):c.1852_1856delinsGGG (p.Asn618fs)	ASPH	Pathogenic	no assertion criteria provided
2429371	NM_004318.4(ASPH):c.1394del (p.Leu465fs)	ASPH	Pathogenic	criteria provided, single submitter
3776052	NM_004318.4(ASPH):c.1552G>T (p.Gly518Ter)	ASPH	Pathogenic	criteria provided, single submitter
3900997	NM_004318.4(ASPH):c.1724G>A (p.Trp575Ter)	ASPH	Pathogenic	criteria provided, single submitter
4531227	NM_004318.4(ASPH):c.1910del (p.Asn637fs)	ASPH	Pathogenic	criteria provided, single submitter
623642	NM_004318.4(ASPH):c.171G>A (p.Trp57Ter)	ASPH	Pathogenic	no assertion criteria provided
137615	NM_004318.4(ASPH):c.2203C>T (p.Arg735Trp)	ASPH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691259	NM_004318.4(ASPH):c.1626G>A (p.Glu542=)	ASPH	Likely pathogenic	criteria provided, single submitter
3065095	NM_004318.4(ASPH):c.1680G>A (p.Trp560Ter)	ASPH	Likely pathogenic	criteria provided, single submitter
3779356	NM_004318.4(ASPH):c.1171_1175del (p.Lys391fs)	ASPH	Likely pathogenic	criteria provided, single submitter
3900998	NM_004318.4(ASPH):c.1747del (p.Tyr583fs)	ASPH	Likely pathogenic	criteria provided, single submitter
4278250	NM_004318.4(ASPH):c.1150-1G>A	ASPH	Likely pathogenic	criteria provided, single submitter
4845927	NM_004318.4(ASPH):c.1764+1G>C	ASPH	Likely pathogenic	criteria provided, single submitter
1333914	NM_004318.4(ASPH):c.197T>C (p.Val66Ala)	ASPH	Uncertain significance	criteria provided, single submitter
1333915	NM_004318.4(ASPH):c.416-2A>G	ASPH	Uncertain significance	criteria provided, single submitter
3779354	NM_004318.4(ASPH):c.323-11842C>T	ASPH	Uncertain significance	criteria provided, single submitter
3779355	NM_004318.4(ASPH):c.323-11677C>T	ASPH	Uncertain significance	criteria provided, single submitter
3779357	NM_004318.4(ASPH):c.322+12706_322+12707insTCCCAGAA	ASPH	Uncertain significance	criteria provided, single submitter
4277910	NM_004318.4(ASPH):c.1627G>A (p.Ala543Thr)	ASPH	Uncertain significance	criteria provided, single submitter
1179236	NM_004318.4(ASPH):c.935-92A>G	ASPH	Benign	criteria provided, multiple submitters, no conflicts
1192457	NM_004318.4(ASPH):c.2127-6C>T	ASPH	Benign	criteria provided, multiple submitters, no conflicts
1192458	NM_004318.4(ASPH):c.1900+6T>C	ASPH	Benign	criteria provided, multiple submitters, no conflicts
1192459	NM_004318.4(ASPH):c.1626+10A>G	ASPH	Benign	criteria provided, multiple submitters, no conflicts
1192460	NM_004318.4(ASPH):c.1437+27G>A	ASPH	Benign	criteria provided, multiple submitters, no conflicts
1192461	NM_004318.4(ASPH):c.1301-79C>G	ASPH	Benign	criteria provided, multiple submitters, no conflicts
1192480	NM_004318.4(ASPH):c.1150-57G>A	ASPH	Benign	criteria provided, multiple submitters, no conflicts

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
ASPH	Strong	Autosomal recessive	facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ASPH	Orphanet:412022	Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs 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
ASPH	HGNC:757	ENSG00000198363	Q12797	Aspartyl/asparaginyl beta-hydroxylase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ASPH	Aspartyl/asparaginyl beta-hydroxylase	Specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins.

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)
ASPH	Enzyme (other)	yes	1.14.11.16	Asp/Arg/Pro-Hydrxlase, Asp-B-hydro/Triadin_dom, TPR-like_helical_dom_sf

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
calcaneal tendon	1
palpebral conjunctiva	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ASPH	289	ubiquitous	marker	calcaneal tendon, stromal cell of endometrium, palpebral conjunctiva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ASPH	1,866

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ASPH	Q12797	43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Protein hydroxylation	1	543.8×	0.012	ASPH
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1	423.0×	0.012	ASPH
Ion homeostasis	1	203.9×	0.016	ASPH
Stimuli-sensing channels	1	135.9×	0.017	ASPH
Cardiac conduction	1	108.8×	0.017	ASPH
Ion channel transport	1	96.0×	0.017	ASPH
Muscle contraction	1	77.2×	0.019	ASPH
Transport of small molecules	1	25.1×	0.050	ASPH
Post-translational protein modification	1	19.2×	0.058	ASPH
Metabolism of proteins	1	12.4×	0.081	ASPH

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
obsolete regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity	1	16852.0×	7e-04	ASPH
regulation of protein depolymerization	1	16852.0×	7e-04	ASPH
activation of store-operated calcium channel activity	1	3370.4×	0.002	ASPH
regulation of cell communication by electrical coupling	1	2407.4×	0.002	ASPH
positive regulation of calcium ion transport into cytosol	1	1203.7×	0.003	ASPH
detection of calcium ion	1	1123.5×	0.003	ASPH
limb morphogenesis	1	1053.2×	0.003	ASPH
response to ATP	1	991.3×	0.003	ASPH
positive regulation of proteolysis	1	802.5×	0.003	ASPH
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1	674.1×	0.003	ASPH
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	1	674.1×	0.003	ASPH
positive regulation of intracellular protein transport	1	674.1×	0.003	ASPH
face morphogenesis	1	495.6×	0.004	ASPH
pattern specification process	1	468.1×	0.004	ASPH
calcium ion homeostasis	1	443.5×	0.004	ASPH
regulation of cytosolic calcium ion concentration	1	383.0×	0.004	ASPH
roof of mouth development	1	247.8×	0.006	ASPH
calcium ion transmembrane transport	1	210.7×	0.006	ASPH
muscle contraction	1	208.1×	0.006	ASPH
cellular response to calcium ion	1	200.6×	0.006	ASPH
regulation of protein stability	1	125.8×	0.009	ASPH
cell population proliferation	1	102.8×	0.011	ASPH
negative regulation of cell population proliferation	1	42.1×	0.025	ASPH
positive regulation of DNA-templated transcription	1	27.9×	0.036	ASPH

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ASPH	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ASPH	13	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	ASPH
ROXADUSTAT	4	ASPH
VENETOCLAX	4	ASPH
DAPRODUSTAT	4	ASPH
VADADUSTAT	4	ASPH
BELINOSTAT	4	ASPH
BLEOMYCIN	4	ASPH
MIDOSTAURIN	4	ASPH
ENARODUSTAT	3	ASPH
NAVITOCLAX	3	ASPH
DESIDUSTAT	3	ASPH
GOSSYPOL	3	ASPH
ABT 737	1	ASPH

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ASPH	15	Binding:15

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ASPH	1.14.11.16	peptide-aspartate beta-dioxygenase

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

13 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.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	ASPH
ROXADUSTAT	4	ASPH
VENETOCLAX	4	ASPH
DAPRODUSTAT	4	ASPH
VADADUSTAT	4	ASPH
BELINOSTAT	4	ASPH
BLEOMYCIN	4	ASPH
MIDOSTAURIN	4	ASPH
ENARODUSTAT	3	ASPH
NAVITOCLAX	3	ASPH
DESIDUSTAT	3	ASPH
GOSSYPOL	3	ASPH
ABT 737	1	ASPH

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ASPH
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.