Corneal disorder

Summary

Corneal disorder (MONDO:0000942) is a disease (an umbrella term covering 24 Mondo subtypes) with 1 cohort gene (13 GWAS associations across 17 studies) and 67 clinical trials. Top therapeutic interventions include belantamab mafodotin, cenegermin, and homatropine.

At a glance

• Umbrella term: 24 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 13
• ClinVar variants: 1
• Clinical trials: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	corneal disorder
Mondo ID	MONDO:0000942
EFO	EFO:0009464
MeSH	D003316
DOID	DOID:10124
ICD-11	980864631
NCIT	C26731
SNOMED CT	15250008
UMLS	C0010034
MedGen	3617
Anatomy (UBERON)	UBERON:0000964
Is cancer (heuristic)	no

Also known as: cornea disease · cornea disease or disorder · corneal disease · corneal disorder · disease of cornea · disease or disorder of cornea · disorder of cornea

Data availability: 1 ClinVar variant · 13 GWAS associations (17 studies).

Disease family

An umbrella term covering 24 Mondo subtypes.

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

Related subtypes (119): ptosis, eye accommodation disease, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Subtypes (24): cornea plana, pseudopterygium, corneal deposit, Bowman’s membrane folds or rupture, corneal degeneration, corneal staphyloma, corneal argyrosis, corneal ectasia, keratopathy, keratitis, corneal edema, brittle cornea syndrome, megalocornea, X-linked corneal dermoid, Peters anomaly, pellucid marginal degeneration, keratoconus, corneal dystrophy, sclerocornea, cornea neoplasm, Arnold stickler bourne syndrome, limbal stem cell deficiency, thygeson superficial punctate keratopathy, Terrien marginal degeneration

Genetics & variants

GWAS landscape

13 GWAS associations across 17 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11659764	2e-276	TCF4 - LINC01415	T	0.86
rs1200108	2e-19	LINC00970, LINC00970	G	0.12
rs1200103	1e-18	LINC00970, LINC00970	C	0.12
rs4075897	3e-15	RXRA - COL5A1	G	0.12
rs10873768	2e-14	COL24A1 - LINC02795	T	0.13
rs368850775	2e-12	LRP1B - UBE2V1P14	G	2.67
rs80095409	4e-12	LAMB1	G	0.33
rs17739131	8e-12	KRT3 - KRT4	C	0.17
rs10929112	1e-07	CEP19P1 - AGAP1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475861	Verma A	2024	11,558	428,433	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473400	UK Biobank Whole-Genome Sequencing Consortium	2025	5,385	453,055	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90477655	Verma A	2024	2,722	115,607	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480065	Verma A	2024	2,722	115,607	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90297612	Auwerx C	2024	2,486	279,248	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297666	Auwerx C	2024	2,486	279,248	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297715	Auwerx C	2024	2,486	279,248	Rare copy-number variants as modulators of common disease susceptibility.
GCST90297760	Auwerx C	2024	2,486	279,248	Rare copy-number variants as modulators of common disease susceptibility.
GCST90103398	Fitzgerald T	2022	1,259	169,498	CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.
GCST90079883	Backman JD	2021	1,087	385,500	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	2
Tier 4: intronic/intergenic	6

MAF distribution

Bucket	Variants
common (>=0.05)	6
low_freq (0.01-0.05)	2
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	3
intergenic_variant	3
regulatory_region_variant	2
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11659764	18	55668281	T>A,G	0.036	intron_variant	TCF4 - LINC01415	2e-276	Tier 4: intronic/intergenic
rs1200108	1	169088731	G>A	0.346	intron_variant	LINC00970, LINC00970	2e-19	Tier 4: intronic/intergenic
rs1200103	1	169083679	C>G,T	0.292	intron_variant	LINC00970, LINC00970	1e-18	Tier 4: intronic/intergenic
rs4075897	9	134625181	G>C,T	0.32	regulatory_region_variant	RXRA - COL5A1	3e-15	Tier 3: regulatory
rs10873768	1	86247838	T>A,G	0.205	regulatory_region_variant	COL24A1 - LINC02795	2e-14	Tier 3: regulatory
rs368850775	2	142492570	G>A	0	intergenic_variant	LRP1B - UBE2V1P14	2e-12	Tier 4: intronic/intergenic
rs80095409	7	107959766	G>A,C	0.012	missense_variant	LAMB1	4e-12	Tier 1: coding
rs17739131	12	52804113	C>G,T	0.061	intergenic_variant	KRT3 - KRT4	8e-12	Tier 4: intronic/intergenic
rs10929112	2	235253338	C>T	0.05	intergenic_variant	CEP19P1 - AGAP1	1e-07	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4072107	NM_001143981.2(CHRDL1):c.176T>A (p.Leu59Ter)	CHRDL1	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
CHRDL1	Orphanet:91489	Isolated congenital megalocornea

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
CHRDL1	HGNC:29861	ENSG00000101938	Q9BU40	Chordin-like protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHRDL1	Chordin-like protein 1	Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors.

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)
CHRDL1	Other/Unknown	no		VWF_dom, CHRDL_1/2_C, CHRDL1/2

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
parietal pleura	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHRDL1	255	broad	marker	decidua, vena cava, parietal pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHRDL1	1,294

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CHRDL1	Q9BU40	69.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Signaling by BMP	1	356.9×	0.008	CHRDL1
Post-translational protein phosphorylation	1	100.2×	0.012	CHRDL1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.012	CHRDL1

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
AMPA glutamate receptor clustering	1	3370.4×	0.002	CHRDL1
embryonic axis specification	1	2407.4×	0.002	CHRDL1
excitatory chemical synaptic transmission	1	1296.3×	0.003	CHRDL1
synapse maturation	1	936.2×	0.003	CHRDL1
eye development	1	351.1×	0.005	CHRDL1
negative regulation of BMP signaling pathway	1	290.6×	0.005	CHRDL1
regulation of synaptic plasticity	1	259.3×	0.005	CHRDL1
ossification	1	227.7×	0.005	CHRDL1
BMP signaling pathway	1	200.6×	0.006	CHRDL1
cell differentiation	1	29.1×	0.034	CHRDL1

Therapeutics

Drugs indicated for this disease

2 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Cyclosporine	Approved (phase 4)
Ex Vivo Expanded Autologous Human Corneal Epithelial Cells Containing Stem Cells	Approved (phase 4)

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
CHRDL1	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	CHRDL1

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)
CHRDL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 67.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	49
PHASE1/PHASE2	5
PHASE1	4
PHASE4	3
PHASE3	3
EARLY_PHASE1	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05045053	PHASE4	UNKNOWN	Efficacy of Xiidra in Dry Eye Disease After Collagen Cross Linking
NCT06294015	PHASE4	UNKNOWN	Efficacy of 20% Autologous Serum Drops in the Treatment of Corneal Epitheliopathy Associated With Antihypertensive Glaucoma Drops.
NCT06636708	PHASE4	COMPLETED	Efficacy of Nanodropper-mediated Topical Anesthetic
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT00447187	PHASE3	TERMINATED	Study to Assess the Efficacy and Safety of LX201 for Prevention of Corneal Allograft Rejection Episodes and Graft Failure in Subjects at Increased Immunological Risk
NCT03436576	PHASE3	UNKNOWN	Efficacy of Two Concentrations of Autologous Serum for the Treatment of Severe Dry Eye
NCT05573802	PHASE1/PHASE2	RECRUITING	A Study to Investigate Safety and Clinical Activity of Belantamab Mafodotin in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma
NCT05581875	PHASE1/PHASE2	NOT_YET_RECRUITING	A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed/ Refractory Multiple Myeloma Previously Treated With One Line Therapy Who Are Lenalidomide Refractory
NCT02148016	PHASE1/PHASE2	UNKNOWN	Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation
NCT03029104	PHASE2	TERMINATED	Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas
NCT04484402	PHASE1/PHASE2	COMPLETED	Treatment of Patients With Inflammatory-dystrophic Diseases of the Cornea Using Autologous Stem Cells
NCT05280275	PHASE1/PHASE2	UNKNOWN	A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Transplant Ineligible
NCT02374723	PHASE1	WITHDRAWN	Evaluation of Biosynthetic Constructs to Replace Donor Corneas
NCT05052554	PHASE1	WITHDRAWN	Study With QR-504a to Evaluate Safety, Tolerability & Corneal Endothelium Molecular Biomarker(s) in Subjects With FECD3
NCT05700864	PHASE1	WITHDRAWN	NGF Treatment for Patients With Neuropathic Corneal Pain
NCT07132437	PHASE1	COMPLETED	Phase I Clinical Study of ZKY001 Eye Drops in the Treatment of Corneal Epithelial Defect
NCT06451172	EARLY_PHASE1	RECRUITING	Novel Antisense Oligonucleotide Eye Drops for Treating Antibiotic-Resistant Bacterial Keratitis
NCT01141985	EARLY_PHASE1	COMPLETED	New Disposable Contact Lens Patient Interface For The Lensx Laser
NCT04232982	Not specified	RECRUITING	The Role of Transscleral Cyclophotocoagulation in Patients Undergoing a Boston Keratoprosthesis
NCT04251143	Not specified	RECRUITING	Dresden Corneal Disease and Treatment Study
NCT06211218	Not specified	RECRUITING	Artificial Intelligence for Screening of Multiple Corneal Diseases
NCT06904560	Not specified	NOT_YET_RECRUITING	The Relation Between BSS Solution Temperature and Endothelial Cells and Post Phaco Discomfort
NCT06967792	Not specified	RECRUITING	Evaluation of the Safety of Terahertz Scanning System on Corneas
NCT06983652	Not specified	RECRUITING	Validation of the Use of Terahertz Scanning System on Corneal Scars and Corneal Edema
NCT07024719	Not specified	RECRUITING	4D Duke Microscope Integrated Optical Coherence Tomography in a Zeiss Artevo 800
NCT07149740	Not specified	RECRUITING	Data Gathering for A10900
NCT07435142	Not specified	NOT_YET_RECRUITING	A Single-Center Clinical Study to Evaluate the Efficacy and Safety of Autologous Urine-Derived Epithelial Cells in the Treatment of Corneal Endothelial Cell Dysfunction
NCT07566806	Not specified	RECRUITING	Evaluation of the Clinical Efficacy and Mechanisms of Cord Plasma Eye Drops in the Treatment of Neuropathic Corneal Pain
NCT07608367	Not specified	NOT_YET_RECRUITING	A Single-Center Clinical Study to Evaluate the Efficacy and Safety of a Suture-Free Ophthalmic Hydrogel for Ocular Surface Tissue Adhesion
NCT00001310	Not specified	TERMINATED	Tissue Studies of Human Eye Diseases
NCT00006411	Not specified	COMPLETED	Cornea Donor Study
NCT00008541	Not specified	COMPLETED	Evaluation and Treatment of Patients With Corneal and External Diseases
NCT00029185	Not specified	COMPLETED	Study of Dehydrex in Patients With Corneal Erosion
NCT00050466	Not specified	COMPLETED	Dynamic Light Scattering and Keratoscopy for Corneal Examination
NCT00343473	Not specified	COMPLETED	Novel Diagnostics With Optical Coherence Tomography: Imaging the Anterior Eye
NCT00357435	Not specified	COMPLETED	Studies in Families With Corneal Dystrophy or Other Inherited Corneal Diseases
NCT00396188	Not specified	COMPLETED	Screening Aid to Identify Corneas That May Have Pathologies or Other Conditions
NCT00491439	Not specified	COMPLETED	Using in Vivo Confocal Microscope to Evaluate the Corneal Wound Healing After Various Ocular Surgeries
NCT00654888	Not specified	COMPLETED	Automated Lamellar Keratectomy in Symptomatic Patients With Bullous Keratopathy
NCT00804505	Not specified	COMPLETED	Hybrid SA RGP Center/S-H Skirt Daily Wear 90 Day Multicenter Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BELANTAMAB MAFODOTIN	4	4
CENEGERMIN	4	1
HOMATROPINE	4	1
INSULIN HUMAN	4	1
LIFITEGRAST	4	1
NIROGACESTAT	4	1
PROPARACAINE	4	1
MAXACALCITOL	3	1