Eye disorder

Summary

Eye disorder (MONDO:0005328) is a disease (an umbrella term covering 120 Mondo subtypes) caused by EPHA2 (GenCC Strong), with 2 cohort genes (103 GWAS associations across 89 studies) and 213 clinical trials. Top therapeutic interventions include brimonidine, timolol, and lisinopril anhydrous.

At a glance

• Causal gene: EPHA2 (GenCC Strong)
• Umbrella term: 120 Mondo subtypes
• Cohort genes: 2
• GWAS associations: 103
• ClinVar variants: 1
• Clinical trials: 213

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	eye disorder
Mondo ID	MONDO:0005328
EFO	EFO:0003966
MeSH	D005128
DOID	DOID:1242, DOID:5614
NCIT	C26767
SNOMED CT	371405004
UMLS	C0015397
MedGen	5092
Anatomy (UBERON)	UBERON:0000019, UBERON:0010230
Is cancer (heuristic)	no

Also known as: disease of eye · disease of eyeball of camera-type eye · disease or disorder of eyeball of camera-type eye · disorder of eye · disorder of eyeball of camera-type eye · eye disease · eye disorder · eyeball of camera-type eye disease · eyeball of camera-type eye disease or disorder · globe disease

Data availability: 1 ClinVar variant · 103 GWAS associations (89 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 120 Mondo subtypes.

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

Related subtypes (3): eye adnexa disorder, orbit neoplasm, orbital dermoid cyst

Subtypes (120): ptosis, eye accommodation disease, corneal disorder, 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

Genetics & variants

GWAS landscape

103 GWAS associations across 89 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr10:122454155	6e-65		A	0.17
chr1:196694783	2e-50		T	0.13
rs12193446	1e-33	LAMA2	?
rs524952	1e-27	LINC02252 - GJD2	?
rs7744813	5e-23	KCNQ5	?
rs11606250	1e-20	LRRC4C	?
rs7184522	4e-18	RBFOX1	?
chr17:79614932	4e-18		?
chr6:32658661	1e-16		T	0.08
rs10089517	6e-16	TOX-DT - RNA5SP267	?
rs138650617	6e-16	BICC1	?
rs10529326	3e-15	TMCO1	?
rs3138142	7e-14	RDH5	?
rs10824539	8e-14	KCNMA1	?
rs7678123	4e-13	CFAP299	?
rs530084015	4e-13	MIR8062 - RN7SL547P	C	1.98
rs184845740	4e-13	CRTAM	A	2.08
rs145188340	5e-13	RNU6-187P - RNA5SP112	C	2.56
rs9273342	5e-13	HLA-DQA1 - HLA-DQB1	T	0.14
rs577395337	1e-12	SPART	C	3.44
rs12950511	2e-12	FLJ40194	?
rs546122907	6e-12	CBFA2T3	G	2.64
rs193003441	6e-12	LINC02852 - NA	G	3.27
rs542341099	7e-12	SPATA33	G	2.84
rs2573222	1e-11	ECEL1 - PRSS56	?
rs576382101	1e-11	RBMXP1 - PRR11P1	T	2.19
rs145461925	1e-11	RNU5A-7P - C12orf56	C	2.45
rs2472493	2e-11	ABCA1 - CT70	?
rs562130172	2e-11	PCP4 - DSCAM	T	2.56
rs562944778	2e-11	RARB	G	2.13

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90044334	Jiang L	2021	115,304	32,675	A generalized linear mixed model association tool for biobank-scale data.
GCST90038600	Donertas HM	2021	83,484	401,114	Common genetic associations between age-related diseases.
GCST90078870	Backman JD	2021	68,925	360,799	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90082856	Backman JD	2021	68,925	360,799	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90042878	Jiang L	2021	65,649	389,331	A generalized linear mixed model association tool for biobank-scale data.
GCST90134550	Xue Z	2022	43,877	44,373	Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank.
GCST90038640	Donertas HM	2021	19,915	464,683	Common genetic associations between age-related diseases.
GCST90079435	Backman JD	2021	8,734	29,064	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083421	Backman JD	2021	8,734	29,064	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90044339	Jiang L	2021	8,289	139,690	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	48

MAF distribution

Bucket	Variants
common (>=0.05)	23
low_freq (0.01-0.05)	0
rare (<0.01)	19
unknown	8

Functional consequences

Consequence	Count
intron_variant	30
unknown	8
intergenic_variant	7
non_coding_transcript_exon_variant	2
synonymous_variant	1
3_prime_UTR_variant	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr10:122454155							6e-65	Tier 4: intronic/intergenic
chr1:196694783							2e-50	Tier 4: intronic/intergenic
rs12193446	6	129498893	A>G	0.05	intron_variant	LAMA2	1e-33	Tier 4: intronic/intergenic
rs524952	15	34713685	T>A,C	0.05	intron_variant	LINC02252 - GJD2	1e-27	Tier 4: intronic/intergenic
rs7744813	6	72933566	C>A,G,T	0.05	intron_variant	KCNQ5	5e-23	Tier 4: intronic/intergenic
rs11606250	11	40127750	G>A	0.05	intron_variant	LRRC4C	1e-20	Tier 4: intronic/intergenic
rs7184522	16	7410698	A>G	0.05	intron_variant	RBFOX1	4e-18	Tier 4: intronic/intergenic
chr17:79614932							4e-18	Tier 4: intronic/intergenic
chr6:32658661							1e-16	Tier 4: intronic/intergenic
rs10089517	8	59266162	C>A	0.05	intron_variant	TOX-DT - RNA5SP267	6e-16	Tier 4: intronic/intergenic
rs138650617	10	58575314	C>CA	0.05	intron_variant	BICC1	6e-16	Tier 4: intronic/intergenic
rs10529326	1	165750115	A>ATCTT	0.05	intron_variant	TMCO1	3e-15	Tier 4: intronic/intergenic
rs3138142	12	55721801	C>A,T	0.05	synonymous_variant	RDH5	7e-14	Tier 4: intronic/intergenic
rs10824539	10	77397375	A>C	0.05	intron_variant	KCNMA1	8e-14	Tier 4: intronic/intergenic
rs7678123	4	80451251	G>A,C	0.05	intron_variant	CFAP299	4e-13	Tier 4: intronic/intergenic
rs530084015	20	7557366	C>T	0.001	intergenic_variant	MIR8062 - RN7SL547P	4e-13	Tier 4: intronic/intergenic
rs184845740	11	122848161	A>G	0.002	intron_variant	CRTAM	4e-13	Tier 4: intronic/intergenic
rs145188340	2	177027148	C>T	0.001	intron_variant	RNU6-187P - RNA5SP112	5e-13	Tier 4: intronic/intergenic
rs9273342	6	32655666	T>C,G	0.183	intergenic_variant	HLA-DQA1 - HLA-DQB1	5e-13	Tier 4: intronic/intergenic
rs577395337	13	36322179	C>G,T	0.001	intron_variant	SPART	1e-12	Tier 4: intronic/intergenic
rs12950511	17	49243576	C>T	0.05	intergenic_variant	FLJ40194	2e-12	Tier 4: intronic/intergenic
rs546122907	16	88889516	G>A	0	intron_variant	CBFA2T3	6e-12	Tier 4: intronic/intergenic
rs193003441	15	95080126	G>A	0	non_coding_transcript_exon_variant	LINC02852 - NA	6e-12	Tier 4: intronic/intergenic
rs542341099	16	89668122	G>A,C	0	intron_variant	SPATA33	7e-12	Tier 4: intronic/intergenic
rs2573222	2	232509806	G>A,C	0.05	intron_variant	ECEL1 - PRSS56	1e-11	Tier 4: intronic/intergenic
rs576382101	6	48663495	T>A	0.001	intergenic_variant	RBMXP1 - PRR11P1	1e-11	Tier 4: intronic/intergenic
rs145461925	12	64263332	C>A,T	0.001	intron_variant	RNU5A-7P - C12orf56	1e-11	Tier 4: intronic/intergenic
rs2472493	9	104933567	G>A,C,T	0.05	intron_variant	ABCA1 - CT70	2e-11	Tier 4: intronic/intergenic
rs562130172	21	39994217	T>C	0.001	intergenic_variant	PCP4 - DSCAM	2e-11	Tier 4: intronic/intergenic
rs562944778	3	25253113	G>T	0.001	intron_variant	RARB	2e-11	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
190959	NM_145200.5(CABP4):c.646C>T (p.Arg216Ter)	CABP4	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 6 · 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
EPHA2	Definitive	Autosomal dominant	cataract 6 multiple types	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPHA2	Orphanet:441447	Early-onset posterior subcapsular cataract
EPHA2	Orphanet:98991	Early-onset nuclear cataract
EPHA2	Orphanet:98993	Early-onset posterior polar cataract
EPHA2	Orphanet:98994	Total early-onset cataract
CABP4	Orphanet:714070	Incomplete congenital stationary night blindness, Schubert-Bornschein type
CABP4	Orphanet:98784	Sleep-related hypermotor epilepsy

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
EPHA2	HGNC:3386	ENSG00000142627	P29317	Ephrin type-A receptor 2	gencc
CABP4	HGNC:1386	ENSG00000175544	P57796	Calcium-binding protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPHA2	Ephrin type-A receptor 2	Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.
CABP4	Calcium-binding protein 4	Involved in normal synaptic function through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals and in auditory transmission.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPHA2	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
CABP4	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS

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
esophagus mucosa	1
lower esophagus mucosa	1
pharyngeal mucosa	1
cardia of stomach	1
vena cava	1
ventral tegmental area	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPHA2	224	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa
CABP4	226	broad	marker	vena cava, cardia of stomach, ventral tegmental area

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPHA2	4,794
CABP4	1,897

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPHA2	P29317	103

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CABP4	P57796	65.01

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 2 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
EPHA-mediated growth cone collapse	1	380.7×	0.008	EPHA2
RHOV GTPase cycle	1	285.5×	0.008	EPHA2
RHOU GTPase cycle	1	278.5×	0.008	EPHA2
RND1 GTPase cycle	1	265.6×	0.008	EPHA2
RND3 GTPase cycle	1	259.6×	0.008	EPHA2
RND2 GTPase cycle	1	259.6×	0.008	EPHA2
EPH-ephrin mediated repulsion of cells	1	219.6×	0.008	EPHA2
EPH-Ephrin signaling	1	165.5×	0.009	EPHA2
RHOG GTPase cycle	1	148.3×	0.009	EPHA2
RAC2 GTPase cycle	1	126.9×	0.009	EPHA2
RAC3 GTPase cycle	1	119.0×	0.009	EPHA2
RAC1 GTPase cycle	1	61.1×	0.016	EPHA2

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
notochord cell development	1	8426.0×	0.004	EPHA2
axial mesoderm formation	1	4213.0×	0.004	EPHA2
notochord formation	1	2808.7×	0.004	EPHA2
negative regulation of lymphangiogenesis	1	2808.7×	0.004	EPHA2
cAMP metabolic process	1	2106.5×	0.004	EPHA2
pericyte cell differentiation	1	1685.2×	0.004	EPHA2
photoreceptor cell morphogenesis	1	1404.3×	0.004	CABP4
regulation of blood vessel endothelial cell migration	1	1404.3×	0.004	EPHA2
retinal bipolar neuron differentiation	1	1404.3×	0.004	CABP4
blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	1203.7×	0.004	EPHA2
negative regulation of chemokine production	1	1053.2×	0.004	EPHA2
lens fiber cell morphogenesis	1	1053.2×	0.004	EPHA2
regulation of lamellipodium assembly	1	936.2×	0.004	EPHA2
positive regulation of bicellular tight junction assembly	1	842.6×	0.004	EPHA2
mammary gland epithelial cell proliferation	1	766.0×	0.004	EPHA2
retinal cone cell development	1	702.2×	0.004	CABP4
branching involved in mammary gland duct morphogenesis	1	702.2×	0.004	EPHA2
response to growth factor	1	702.2×	0.004	EPHA2
negative regulation of cell adhesion mediated by integrin	1	648.1×	0.004	EPHA2
bone remodeling	1	468.1×	0.005	EPHA2
post-anal tail morphogenesis	1	366.4×	0.006	EPHA2
activation of GTPase activity	1	366.4×	0.006	EPHA2
central nervous system neuron differentiation	1	300.9×	0.007	EPHA2
regulation of ERK1 and ERK2 cascade	1	290.6×	0.007	EPHA2
neural tube development	1	263.3×	0.007	EPHA2
phototransduction	1	247.8×	0.007	CABP4
regulation of angiogenesis	1	210.7×	0.008	EPHA2
cell motility	1	200.6×	0.009	EPHA2
osteoclast differentiation	1	172.0×	0.009	EPHA2
ephrin receptor signaling pathway	1	172.0×	0.009	EPHA2

Therapeutics

Drugs indicated for this disease

41 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetylcysteine	Approved (phase 4)
Alclometasone Dipropionate	Approved (phase 4)
Alteplase	Approved (phase 4)
Ascorbic Acid	Approved (phase 4)
Bendazac	Approved (phase 4)
Betamethasone	Approved (phase 4)
Bromfenac	Approved (phase 4)
Cenegermin	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Cyclosporine	Approved (phase 4)
Cysteamine	Approved (phase 4)
Desonide	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Dexpanthenol	Approved (phase 4)
Diclofenac	Approved (phase 4)
Difluprednate	Approved (phase 4)
Fluocinolone Acetonide	Approved (phase 4)
Fluorometholone	Approved (phase 4)
Flurbiprofen	Approved (phase 4)
Heparin	Approved (phase 4)
Hydrocortisone	Approved (phase 4)
Indomethacin	Approved (phase 4)
Ketorolac	Approved (phase 4)
Lifitegrast	Approved (phase 4)
Loteprednol Etabonate	Approved (phase 4)
Medrysone	Approved (phase 4)
Nepafenac	Approved (phase 4)
Ocriplasmin	Approved (phase 4)
Pegcetacoplan	Approved (phase 4)
Piroxicam	Approved (phase 4)
Potassium Iodide	Approved (phase 4)
Prednisolone	Approved (phase 4)
Retinol	Approved (phase 4)
Riboflavin	Approved (phase 4)
Rimexolone	Approved (phase 4)
Salicylic Acid	Approved (phase 4)
Sirolimus	Approved (phase 4)
Sodium Chloride	Approved (phase 4)
Triamcinolone	Approved (phase 4)
Varenicline	Approved (phase 4)
Voretigene Neparvovec	Approved (phase 4)
Inosine	Phase 3 (in late-stage trials)
Phenylephrine	Phase 3 (in late-stage trials)
Tropicamide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): AMA0076, Anecortave Acetate, Azithromycin, Hydrocodone.

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
EPHA2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPHA2	50	4
CABP4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	EPHA2
FEDRATINIB	4	EPHA2
TIVOZANIB	4	EPHA2
SORAFENIB	4	EPHA2
DASATINIB ANHYDROUS	4	EPHA2
REGORAFENIB	4	EPHA2
CABOZANTINIB	4	EPHA2
VANDETANIB	4	EPHA2
NILOTINIB	4	EPHA2
BOSUTINIB	4	EPHA2
TOVORAFENIB	4	EPHA2
NINTEDANIB	4	EPHA2
DASATINIB	4	EPHA2
CRIZOTINIB	4	EPHA2
SARACATINIB	3	EPHA2
LINIFANIB	3	EPHA2
TESEVATINIB	3	EPHA2
ALVOCIDIB	3	EPHA2
ALISERTIB	3	EPHA2
LESTAURTINIB	3	EPHA2
DORAMAPIMOD	2	EPHA2
NEFLAMAPIMOD	2	EPHA2
FORETINIB	2	EPHA2
ILORASERTIB	2	EPHA2
CEP-32496	2	EPHA2
BAFETINIB	2	EPHA2
SAPITINIB	2	EPHA2
OSI-632	2	EPHA2
GOLVATINIB	2	EPHA2
PEXMETINIB	2	EPHA2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
EPHA2	567	Binding:565, Functional:1, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EPHA2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
EPHA2	567

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

30 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)
PONATINIB	4	EPHA2
FEDRATINIB	4	EPHA2
TIVOZANIB	4	EPHA2
SORAFENIB	4	EPHA2
DASATINIB ANHYDROUS	4	EPHA2
REGORAFENIB	4	EPHA2
CABOZANTINIB	4	EPHA2
VANDETANIB	4	EPHA2
NILOTINIB	4	EPHA2
BOSUTINIB	4	EPHA2
TOVORAFENIB	4	EPHA2
NINTEDANIB	4	EPHA2
DASATINIB	4	EPHA2
CRIZOTINIB	4	EPHA2
SARACATINIB	3	EPHA2
LINIFANIB	3	EPHA2
TESEVATINIB	3	EPHA2
ALVOCIDIB	3	EPHA2
ALISERTIB	3	EPHA2
LESTAURTINIB	3	EPHA2
DORAMAPIMOD	2	EPHA2
NEFLAMAPIMOD	2	EPHA2
FORETINIB	2	EPHA2
ILORASERTIB	2	EPHA2
CEP-32496	2	EPHA2
BAFETINIB	2	EPHA2
SAPITINIB	2	EPHA2
OSI-632	2	EPHA2
GOLVATINIB	2	EPHA2
PEXMETINIB	2	EPHA2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	EPHA2
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	CABP4

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)
CABP4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 213.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	137
PHASE2	19
PHASE1	16
PHASE3	13
PHASE1/PHASE2	9
PHASE4	8
PHASE2/PHASE3	7
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07266948	PHASE4	RECRUITING	Impact of TRYPTYR on a Patient’s Quality of Life and Ability to Perform Work
NCT07267299	PHASE4	NOT_YET_RECRUITING	Switching From Restasis to TRYPTYR
NCT07267481	PHASE4	NOT_YET_RECRUITING	Switching From Xiidra to TRYPTYR
NCT07434635	PHASE4	RECRUITING	APPRAISE: Assessment of Pain and Posterior Synechiae Reduction With Atropine, an Investigation of Post-Surgical Eyes
NCT00911924	PHASE4	COMPLETED	A Prospective, Unmasked Evaluation of the iStent in Patients With Primary Open-Angle Glaucoma
NCT00913029	PHASE4	COMPLETED	Evaluation of the iStent Versus Two Ocular Hypotensive Agents in Patients With Primary Open-angle Glaucoma (POAG)
NCT00957190	PHASE4	COMPLETED	The DIOXXACT Trial(Diurnal IOP and OBF Xalatan vs Xalatan And Cosopt Trial)
NCT03148132	PHASE4	COMPLETED	VEGF Concentrations After Intravitreal Bevacizumab vs Ranibizumab as a Treatment for Type 1 ROP
NCT03913143	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
NCT04663750	PHASE3	RECRUITING	Vitrectomy, Subretinal Tissue Plasminogen Activator (TPA) and Intravitreal Gas for Submacular Haemorrhage Secondary to Exudative (Wet) Age-related Macular Degeneration (TIGER).
NCT05276063	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Phase 2b, Study of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)
NCT06112340	PHASE2/PHASE3	RECRUITING	Extension Study of Two Doses of Linsitinib in Subjects With Active, Moderate to Severe Thyroid Eye Disease (TED)
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT00120432	PHASE3	COMPLETED	Single Dose of 1% Tropicamide and 10% Phenylephrine for Pupillary Dilation
NCT00333203	PHASE3	COMPLETED	Next Generation Ophthalmic Irrigating Solution Posterior Segment Study
NCT00370734	PHASE2/PHASE3	UNKNOWN	Effect of Percutaneous Botulinum Toxin A Injection on Natural Course of Upper Lid Retraction in Thyroid Eye Disease
NCT02157077	PHASE3	COMPLETED	Aflibercept After Ranibizumab in Exudative Age-related Macular Degeneration
NCT03954626	PHASE3	COMPLETED	Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
NCT04149210	PHASE3	COMPLETED	FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT05158296	PHASE2/PHASE3	TERMINATED	Study to Evaluate the Efficacy Safety and Tolerability of Ultevursen in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene (Sirius)
NCT05158699	PHASE3	TERMINATED	Effectiveness of Periocular Drug Injection in CATaract Surgery
NCT05176717	PHASE2/PHASE3	TERMINATED	Study to Evaluate the Efficacy Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene With Early to Moderate Vision Loss (Celeste)
NCT05656027	PHASE3	COMPLETED	Phase 3 Evaluation of the Safety and Efficacy of LNZ100 & LNZ101 for the Treatment of Presbyopia
NCT05728944	PHASE3	COMPLETED	Phase 3 Efficacy Study of LNZ100 & LNZ101 for the Treatment of Presbyopia
NCT05753189	PHASE3	COMPLETED	Phase 3 Safety Study of LNZ100 and LNZ101 for the Treatment of Presbyopia Subjects
NCT06045299	PHASE3	COMPLETED	Evaluation of the Efficacy and Safety of LNZ101 and LNZ100 for the Presbyopia
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT06394232	PHASE1/PHASE2	RECRUITING	Safety & Efficacy of Eyecyte-RPE™ in Patients With Geographic Atrophy Secondary to Dry Age-related Macular Degeneration.
NCT07174687	PHASE2	RECRUITING	SGLT2 Inhibitors in Geographic Atrophy
NCT07413172	PHASE2	NOT_YET_RECRUITING	Autologous Serum Tears With Hyaluronate vs Balanced Salt Solution for Moderate-to-Severe Dry Eye
NCT00123279	PHASE2	COMPLETED	Intravitreal Microplasmin in Patients Undergoing Surgical Vitrectomy
NCT00211432	PHASE2	COMPLETED	Treatment of Pseudovitellium Detachment With Open-Label Anecortave Acetate Sterile Suspension (15 mg)
NCT00315640	PHASE2	COMPLETED	Anecortave Acetate for Treatment of Steroid Induced Intraocular Pressure (IOP) Elevation
NCT01016873	PHASE2	COMPLETED	INTREPID - IRay Plus Anti-VEGF Treatment For Patients With Wet AMD
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01494805	PHASE1/PHASE2	COMPLETED	Safety and Efficacy Study of rAAV.sFlt-1 in Patients With Exudative Age-Related Macular Degeneration
NCT01521065	PHASE2	UNKNOWN	An Open-label Study to Evaluate the Clinical and Economic Benefits of I-Ray in Patients With Choroidal Neovascularization Secondary to Age-related Macular Degeneration
NCT01648452	PHASE1/PHASE2	COMPLETED	CNTF Implants for CNGB3 Achromatopsia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BRIMONIDINE	4	8
TIMOLOL	4	3
LISINOPRIL ANHYDROUS	4	2
AFLIBERCEPT	4	1
AMLODIPINE	4	1
ATROPINE	4	1
BETA CAROTENE	4	1
BEVACIZUMAB	4	1
BROMFENAC	4	1
FLUORESCEIN	4	1
FLUOROMETHOLONE	4	1
LATANOPROST	4	1
OCRIPLASMIN	4	1
RANIBIZUMAB	4	1
TRIAMCINOLONE ACETONIDE	4	1
VALPROIC ACID	4	1
ACECLIDINE	3	7
AMA0076	3	3
ANECORTAVE ACETATE	3	2
LINSITINIB	3	2
LAQUINIMOD	3	1
RESVERATROL	3	1
SOZINIBERCEPT	3	1
SEPOFARSEN	2	4
ACOLTREMON	2	3
BENZALKONIUM CHLORIDE	2	1
FOSELUTOCLAX	2	1
ULTEVURSEN	2	1
X-82	2	1
CHEMBL1164123	0	1