Lens subluxation

Summary

Lens subluxation (MONDO:0001271) is a disease with 2 cohort genes and 11 clinical trials.

At a glance

• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lens subluxation
Mondo ID	MONDO:0001271
MeSH	D007906
DOID	DOID:11364
ICD-10-CM	H27.11
ICD-11	254522648
NCIT	C34772
SNOMED CT	65814009
UMLS	C0023316
MedGen	9718
Is cancer (heuristic)	no

Also known as: lens subluxation · lens subluxation (disease) · subluxation of lens

Data availability: 3 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › lens disorder › lens subluxation

Related subtypes (9): posterior dislocation of lens, cataract, blepharoptosis-myopia-ectopia lentis syndrome, classic homocystinuria, facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome, 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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16440	NM_000138.5(FBN1):c.364C>T (p.Arg122Cys)	FBN1	Pathogenic	criteria provided, multiple submitters, no conflicts
523459	NM_001372066.1(TFAP2A):c.1043_1044del (p.Lys348fs)	TFAP2A	Pathogenic	criteria provided, multiple submitters, no conflicts
374079	NM_000138.5(FBN1):c.1481G>T (p.Cys494Phe)	FBN1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFAP2A	Orphanet:1297	Branchio-oculo-facial syndrome
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TFAP2A	HGNC:11742	ENSG00000137203	P05549	Transcription factor AP-2-alpha	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFAP2A	Transcription factor AP-2-alpha	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TFAP2A	Transcription factor	no		TF_AP2, TF_AP2_alpha_N, TF_AP2_C
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

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
gingiva	1
gingival epithelium	1
upper leg skin	1
decidua	1
skin of hip	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFAP2A	220	ubiquitous	marker	upper leg skin, gingival epithelium, gingiva
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBN1	3,640
TFAP2A	2,734

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBN1	P35555	11
TFAP2A	P05549	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TFAP2 (AP-2) family regulates transcription of other transcription factors	1	1427.5×	0.008	TFAP2A
TFAP2 (AP-2) family regulates transcription of cell cycle factors	1	1142.0×	0.008	TFAP2A
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation	1	1142.0×	0.008	TFAP2A
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	571.0×	0.008	TFAP2A
Activation of the TFAP2 (AP-2) family of transcription factors	1	475.8×	0.008	TFAP2A
Positive Regulation of CDH1 Gene Transcription	1	475.8×	0.008	TFAP2A
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	380.7×	0.008	TFAP2A
Developmental Lineage of Mammary Stem Cells	1	380.7×	0.008	TFAP2A
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	317.2×	0.008	TFAP2A
Specification of the neural plate border	1	317.2×	0.008	TFAP2A
SUMOylation of transcription factors	1	285.5×	0.008	TFAP2A
Elastic fibre formation	1	167.9×	0.012	FBN1
TGF-beta receptor signaling activates SMADs	1	163.1×	0.012	FBN1
Molecules associated with elastic fibres	1	154.3×	0.012	FBN1
Regulation of MITF-M-dependent genes involved in pigmentation	1	132.8×	0.012	TFAP2A
Gastrulation	1	129.8×	0.012	TFAP2A
MITF-M-dependent gene expression	1	90.6×	0.017	TFAP2A
Integrin cell surface interactions	1	67.2×	0.021	FBN1
Degradation of the extracellular matrix	1	58.9×	0.023	FBN1
MITF-M-regulated melanocyte development	1	57.1×	0.023	TFAP2A
Post-translational protein phosphorylation	1	50.1×	0.025	FBN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.027	FBN1
RNA Polymerase II Transcription	1	11.3×	0.098	TFAP2A
Gene expression (Transcription)	1	8.9×	0.118	TFAP2A
Generic Transcription Pathway	1	7.5×	0.133	TFAP2A
Developmental Biology	1	7.2×	0.134	TFAP2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
optic cup structural organization	1	8426.0×	0.003	TFAP2A
optic vesicle morphogenesis	1	4213.0×	0.003	TFAP2A
oculomotor nerve formation	1	4213.0×	0.003	TFAP2A
post-embryonic eye morphogenesis	1	2808.7×	0.003	FBN1
positive regulation of tooth mineralization	1	2808.7×	0.003	TFAP2A
obsolete sequestering of BMP in extracellular matrix	1	2106.5×	0.003	FBN1
obsolete sequestering of TGFbeta in extracellular matrix	1	2106.5×	0.003	FBN1
skeletal system development	2	125.8×	0.003	TFAP2A, FBN1
negative regulation of osteoclast development	1	1685.2×	0.003	FBN1
trigeminal nerve development	1	1203.7×	0.003	TFAP2A
cellular response to iron ion	1	1203.7×	0.003	TFAP2A
embryonic eye morphogenesis	1	766.0×	0.005	FBN1
obsolete negative regulation of transcription by competitive promoter binding	1	648.1×	0.005	TFAP2A
cellular response to insulin-like growth factor stimulus	1	648.1×	0.005	FBN1
eyelid development in camera-type eye	1	526.6×	0.006	TFAP2A
negative regulation of reactive oxygen species metabolic process	1	468.1×	0.006	TFAP2A
cell adhesion mediated by integrin	1	337.0×	0.008	FBN1
retina layer formation	1	324.1×	0.008	TFAP2A
bone morphogenesis	1	300.9×	0.008	TFAP2A
embryonic cranial skeleton morphogenesis	1	290.6×	0.008	TFAP2A
negative regulation of osteoclast differentiation	1	271.8×	0.008	FBN1
metanephros development	1	255.3×	0.008	FBN1
embryonic forelimb morphogenesis	1	247.8×	0.008	TFAP2A
regulation of cell differentiation	1	216.1×	0.009	TFAP2A
positive regulation of bone mineralization	1	195.9×	0.009	TFAP2A
camera-type eye development	1	179.3×	0.010	FBN1
lung alveolus development	1	175.5×	0.010	FBN1
inner ear morphogenesis	1	150.5×	0.011	TFAP2A
cellular response to transforming growth factor beta stimulus	1	138.1×	0.011	FBN1
positive regulation of neuron apoptotic process	1	135.9×	0.011	TFAP2A

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
TFAP2A	0	0
FBN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	TFAP2A, FBN1

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)
TFAP2A	0	—
FBN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01346566	PHASE3	COMPLETED	Prospective Study of Cionni Ring and In-the-bag IOL Implantation for Subluxated Lenses
NCT07096622	Not specified	RECRUITING	Efficacy of Visual and Perceptual Training on Visual Function for Operative Congenital Ectopia Lentis Children
NCT07257172	Not specified	RECRUITING	Sutureless Technique for Repositioning and Scleral Fixation of the Capsular Bag - Intraocular Lens Complex With Permanent Use of Iris Retractors
NCT02790268	Not specified	COMPLETED	Ultrasound Biomicroscopic Analysis of Cionni Ring and In-the-bag IOL Implantation for Subluxated Lenses
NCT03752710	Not specified	COMPLETED	Biometry of Occult Lens Subluxation Misdiagnosed as Primary Acute Angle Closed Glaucoma
NCT04062084	Not specified	UNKNOWN	Study of Multifunctional Cataract-assisted Retractor in Complicated Cataract Surgery
NCT04120389	Not specified	UNKNOWN	Efficacy of an Ocular Bandage Contact Lens for the Treatment of Dry Eye After Complicated and Combined Cataract Surgery
NCT04685122	Not specified	UNKNOWN	Study of Subluxation Lens Biometrics and Postoperative Intraocular Lens Stability
NCT05578469	Not specified	UNKNOWN	Surgical Treatment of Marfan Syndrome With Subluxation Lens
NCT06396156	Not specified	COMPLETED	Anterior Versus Posterior Artisan Intraocular Lens Fixation in Aphakic Children With Insufficient Capsular Support.
NCT06627062	Not specified	COMPLETED	A Modified-simple Technique for Managing Moderate and Severe Subluxated Lens Extraction