Aniridia

Summary

Aniridia (MONDO:0019172) is a disease caused by FOXC1 (GenCC Strong), with 10 cohort genes and 20 clinical trials. Top therapeutic interventions include ataluren.

At a glance

• Causal gene: FOXC1 (GenCC Strong)
• Cohort genes: 10
• ClinVar variants: 22
• Clinical trials: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aniridia
Mondo ID	MONDO:0019172
MeSH	D015783
Orphanet	77
DOID	DOID:12271
ICD-10-CM	Q13.1
ICD-11	970699895
NCIT	C84563
SNOMED CT	69278003
UMLS	C0003076
MedGen	1941
GARD	0027869
MedDRA	10002532
Is cancer (heuristic)	no

Also known as: aplasia of iris

Data availability: 22 ClinVar variants · 2 GenCC gene-disease records · 16 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (7): pupil disorder, ciliary body disorder, iritis, exfoliation syndrome, iris neoplasm, anterior segment dysgenesis 3, intraoperative floppy iris syndrome

Subtypes (2): isolated aniridia, Zazam Sheriff Phillips syndrome

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

22 retrieved; paginated sample, class counts are floors:

17 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely benign, 1 not provided, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
267197	NC_000011.10:g.31130456_31671718del	DCDC1	Pathogenic	no assertion criteria provided
267198	NC_000011.10:g.31256273_31773692del	DCDC1	Pathogenic	no assertion criteria provided
267192	NC_000011.8:g.31199000_31914000del715001	ELP4	Pathogenic	no assertion criteria provided
565298	NM_001604.5(PAX6):c.(10+1_11-1)(1311?)del	ELP4	Pathogenic	no assertion criteria provided
1341682	NM_004431.5(EPHA2):c.41G>A (p.Trp14Ter)	EPHA2	Pathogenic	criteria provided, single submitter
267200	NC_000006.10:g.1543591_1675085del131495	FOXC1	Pathogenic	no assertion criteria provided
267191	NC_000011.8:g.31199000_31849000del650001	IMMP1L	Pathogenic	no assertion criteria provided
267201	NC_000004.10:g.111994000_115504000del3510001	LINC02945	Pathogenic	no assertion criteria provided
267196	NC_000011.10:g.30988877_31725876del	LOC105980005	Pathogenic	no assertion criteria provided
267194	NC_000011.8:g.31698271_31794414del96144	LOC106007493	Pathogenic	no assertion criteria provided
267199	NC_000011.10:g.31400877_31729876del	LOC129390272	Pathogenic	no assertion criteria provided
267195	NC_000011.10:g.30896521_31676711del	LOC129390274	Pathogenic	no assertion criteria provided
1710343	NM_001368894.2(PAX6):c.38_41delinsAATCAGC (p.Gly13_Val14delinsGluSerAla)	PAX6	Pathogenic	criteria provided, single submitter
1710345	NM_001368894.2(PAX6):c.410T>A (p.Ile137Lys)	PAX6	Pathogenic	criteria provided, single submitter
1710346	NM_001368894.2(PAX6):c.1017del (p.Tyr340fs)	PAX6	Pathogenic	criteria provided, single submitter
267193	NC_000011.8:g.31779000_31933000del154001	PAX6	Pathogenic	no assertion criteria provided
812365	NM_001368894.2(PAX6):c.10+1G>C	PAX6	Pathogenic	no assertion criteria provided
221954	NM_001042413.2(GLIS3):c.2710G>C (p.Gly904Arg)	GLIS3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1314316	NM_001368894.2(PAX6):c.761G>A (p.Arg254Gln)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
870447	NM_003106.4(SOX2):c.20C>T (p.Thr7Met)	LOC108281177	Uncertain significance	criteria provided, multiple submitters, no conflicts
221953	NM_001173464.2(KIF21A):c.2287G>A (p.Val763Met)	KIF21A	Likely benign	criteria provided, single submitter
585045	NM_001368894.2(PAX6):c.574C>T (p.Gln192Ter)	PAX6	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 25 · Orphanet: 31 · 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
FOXC1	Strong	Autosomal dominant	aniridia	10
PITX2	Moderate	Autosomal dominant	aniridia	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOXC1	Orphanet:250923	Isolated aniridia
FOXC1	Orphanet:708	Peters anomaly
FOXC1	Orphanet:782	Axenfeld-Rieger syndrome
FOXC1	Orphanet:91483	Rieger anomaly
FOXC1	Orphanet:98978	Axenfeld anomaly
PITX2	Orphanet:334	Hereditary atrial fibrillation
PITX2	Orphanet:708	Peters anomaly
PITX2	Orphanet:782	Axenfeld-Rieger syndrome
PITX2	Orphanet:91481	Ring dermoid of cornea
PITX2	Orphanet:91483	Rieger anomaly
PITX2	Orphanet:98978	Axenfeld anomaly
KIF21A	Orphanet:45358	Congenital fibrosis of extraocular muscles
KIF21A	Orphanet:994	Fetal akinesia deformation sequence
GLIS3	Orphanet:79118	Neonatal diabetes-congenital hypothyroidism-congenital glaucoma-hepatic fibrosis-polycystic kidneys syndrome
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
PAX6	Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome
PAX6	Orphanet:2253	Foveal hypoplasia-presenile cataract syndrome
PAX6	Orphanet:2334	Autosomal dominant keratitis
PAX6	Orphanet:250923	Isolated aniridia
PAX6	Orphanet:35737	Morning glory disc anomaly
PAX6	Orphanet:708	Peters anomaly
PAX6	Orphanet:893	WAGR syndrome
PAX6	Orphanet:98942	Coloboma of choroid and retina
PAX6	Orphanet:98943	Coloboma of eye lens
PAX6	Orphanet:98944	Coloboma of iris
PAX6	Orphanet:98945	Coloboma of macula
PAX6	Orphanet:98946	Coloboma of eyelid
PAX6	Orphanet:98947	Coloboma of optic disc

Cohort genes → proteins

10 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FOXC1	HGNC:3800	ENSG00000054598	Q12948	Forkhead box protein C1	gencc,clinvar
PITX2	HGNC:9005	ENSG00000164093	Q99697	Pituitary homeobox 2	gencc
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	clinvar
KIF21A	HGNC:19349	ENSG00000139116	Q7Z4S6	Kinesin-like protein KIF21A	clinvar
DCDC1	HGNC:20625	ENSG00000170959	M0R2J8	Doublecortin domain-containing protein 1	clinvar
IMMP1L	HGNC:26317	ENSG00000148950	Q96LU5	Mitochondrial inner membrane protease subunit 1	clinvar
GLIS3	HGNC:28510	ENSG00000107249	Q8NEA6	Zinc finger protein GLIS3	clinvar
EPHA2	HGNC:3386	ENSG00000142627	P29317	Ephrin type-A receptor 2	clinvar
LINC02945	HGNC:55960	ENSG00000249815		long intergenic non-protein coding RNA 2945	clinvar
PAX6	HGNC:8620	ENSG00000007372	P26367	Paired box protein Pax-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOXC1	Forkhead box protein C1	DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development.
PITX2	Pituitary homeobox 2	May play a role in myoblast differentiation.
ELP4	Elongator complex protein 4	Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).
KIF21A	Kinesin-like protein KIF21A	Processive microtubule plus-end directed motor protein involved in neuronal axon guidance.
DCDC1	Doublecortin domain-containing protein 1	Microtubule-binding protein which plays an important role in mediating dynein-dependent transport of RAB8A-positive vesicles to the midbody during cytokinesis.
IMMP1L	Mitochondrial inner membrane protease subunit 1	Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space.
GLIS3	Zinc finger protein GLIS3	Acts both as a repressor and an activator of transcription.
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.
PAX6	Paired box protein Pax-6	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas.

Protein-family classification

Druggable: 2 · Difficult: 5 · Unknown: 3 · Druggable fraction: 0.2

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	4	3.3×	0.123
Protease	1	3.7×	0.513
Kinase	1	2.8×	0.513
Scaffold/PPI	1	1.7×	0.561
Other/Unknown	3	0.5×	0.976

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FOXC1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
PITX2	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
KIF21A	Scaffold/PPI	no		WD40_rpt, Kinesin_motor_dom, WD40/YVTN_repeat-like_dom_sf
DCDC1	Other/Unknown	no		Doublecortin_dom, Ricin_B-like_lectins, Doublecortin_dom_sf
IMMP1L	Protease	yes		Pept_S26A_signal_pept_1, Peptidase_S26, LexA/Signal_pep-like_sf
GLIS3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
EPHA2	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom
LINC02945	Other/Unknown	no
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

9 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)	10
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	3
primordial germ cell in gonad	2
parotid gland	1
trigeminal ganglion	1
vena cava	1
biceps brachii	1
gingiva	1
gingival epithelium	1
calcaneal tendon	1
dorsal root ganglion	1
pons	1
substantia nigra pars compacta	1
male germ line stem cell (sensu Vertebrata) in testis	1
oviduct epithelium	1
right uterine tube	1
endothelial cell	1
islet of Langerhans	1
buccal mucosa cell	1
epithelial cell of pancreas	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOXC1	267	ubiquitous	marker	parotid gland, vena cava, trigeminal ganglion
PITX2	166	broad	marker	gingiva, biceps brachii, gingival epithelium
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad
KIF21A	253	ubiquitous	marker	dorsal root ganglion, substantia nigra pars compacta, pons
DCDC1	148	broad	marker	oviduct epithelium, right uterine tube, male germ line stem cell (sensu Vertebrata) in testis
IMMP1L	253	ubiquitous	marker	endothelial cell, islet of Langerhans, ventricular zone
GLIS3	213	ubiquitous	marker	buccal mucosa cell, epithelial cell of pancreas, pancreatic ductal cell
EPHA2	224	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, pharyngeal mucosa
LINC02945	98		yes	primordial germ cell in gonad, cortical plate, skeletal muscle tissue
PAX6	201	broad	marker	palpebral conjunctiva, type B pancreatic cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971
EPHA2	4,794
FOXC1	2,896
PITX2	2,389
ELP4	1,740
GLIS3	1,717
KIF21A	1,564
IMMP1L	1,405
DCDC1	3
LINC02945	0

Intra-cohort edges

A	B	Sources
ELP4	IMMP1L	string_interaction
ELP4	PAX6	string_interaction
FOXC1	PAX6	string_interaction
FOXC1	PITX2	intact, string_interaction
IMMP1L	PAX6	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 5 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPHA2	P29317	103
KIF21A	Q7Z4S6	5
PITX2	Q99697	3
PAX6	P26367	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IMMP1L	Q96LU5	87.87
ELP4	Q96EB1	74.49
DCDC1	M0R2J8	68.53
FOXC1	Q12948	56.09
GLIS3	Q8NEA6	49.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. Enrichment computed across 10 evidence-associated genes (6 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 6 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	475.8×	0.049	PITX2
Formation of intermediate mesoderm	1	237.9×	0.049	FOXC1
Formation of the anterior neural plate	1	173.0×	0.049	PAX6
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	146.4×	0.049	PAX6
Regulation of gene expression in beta cells	1	86.5×	0.050	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	86.5×	0.050	PAX6
Formation of the ureteric bud	1	82.8×	0.050	FOXC1
EPHA-mediated growth cone collapse	1	63.4×	0.051	EPHA2
RHOV GTPase cycle	1	47.6×	0.051	EPHA2
RHOU GTPase cycle	1	46.4×	0.051	EPHA2
RND1 GTPase cycle	1	44.3×	0.051	EPHA2
RND3 GTPase cycle	1	43.3×	0.051	EPHA2
RND2 GTPase cycle	1	43.3×	0.051	EPHA2
EPH-ephrin mediated repulsion of cells	1	36.6×	0.056	EPHA2
Kinesins	1	29.7×	0.064	KIF21A
EPH-Ephrin signaling	1	27.6×	0.065	EPHA2
RHOG GTPase cycle	1	24.7×	0.068	EPHA2
Golgi-to-ER retrograde transport	1	22.1×	0.071	KIF21A
RAC2 GTPase cycle	1	21.1×	0.071	EPHA2
RAC3 GTPase cycle	1	19.8×	0.072	EPHA2
COPI-dependent Golgi-to-ER retrograde traffic	1	18.5×	0.073	KIF21A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	17.5×	0.074	KIF21A
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	15.2×	0.081	PAX6
HATs acetylate histones	1	13.2×	0.089	ELP4
Factors involved in megakaryocyte development and platelet production	1	11.1×	0.101	KIF21A
RAC1 GTPase cycle	1	10.2×	0.105	EPHA2
Membrane Trafficking	1	6.2×	0.160	KIF21A
Hemostasis	1	6.0×	0.160	KIF21A
Vesicle-mediated transport	1	5.8×	0.160	KIF21A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of lymphangiogenesis	2	1248.3×	1e-04	FOXC1, EPHA2
lacrimal gland development	2	468.1×	6e-04	FOXC1, PAX6
iris morphogenesis	2	416.1×	6e-04	PAX6, PITX2
pancreatic A cell development	1	1872.4×	0.006	PAX6
subthalamic nucleus development	1	1872.4×	0.006	PITX2
oligodendrocyte cell fate specification	1	1872.4×	0.006	PAX6
forebrain-midbrain boundary formation	1	1872.4×	0.006	PAX6
somatic motor neuron fate commitment	1	1872.4×	0.006	PAX6
notochord cell development	1	1872.4×	0.006	EPHA2
superior vena cava morphogenesis	1	1872.4×	0.006	PITX2
glomerular epithelium development	1	1872.4×	0.006	FOXC1
positive regulation of hematopoietic stem cell differentiation	1	1872.4×	0.006	FOXC1
camera-type eye development	2	79.7×	0.006	FOXC1, PITX2
eye development	2	78.0×	0.006	FOXC1, PAX6
vasculogenesis	2	56.7×	0.006	EPHA2, PITX2
keratinocyte differentiation	2	55.1×	0.006	EPHA2, PAX6
regulation of transcription by RNA polymerase II	5	6.5×	0.006	FOXC1, ELP4, GLIS3, PAX6, PITX2
apoptotic process involved in outflow tract morphogenesis	1	936.2×	0.008	FOXC1
hypothalamus cell migration	1	936.2×	0.008	PITX2
axial mesoderm formation	1	936.2×	0.008	EPHA2
prolactin secreting cell differentiation	1	936.2×	0.008	PITX2
left lung morphogenesis	1	936.2×	0.008	PITX2
pulmonary vein morphogenesis	1	936.2×	0.008	PITX2
cell proliferation involved in outflow tract morphogenesis	1	936.2×	0.008	PITX2
negative regulation of apoptotic process involved in outflow tract morphogenesis	1	936.2×	0.008	FOXC1
positive regulation of core promoter binding	1	936.2×	0.008	FOXC1
negative regulation of transcription by RNA polymerase II	4	7.9×	0.008	FOXC1, GLIS3, PAX6, PITX2
pulmonary myocardium development	1	624.1×	0.008	PITX2
notochord formation	1	624.1×	0.008	EPHA2
habenula development	1	624.1×	0.008	PAX6

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Ataluren.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 9

Druggability breadth: 2 of 10 evidence-associated genes (20%) 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
FOXC1	0	0
PITX2	0	0
ELP4	0	0
KIF21A	0	0
DCDC1	0	0
IMMP1L	0	0
GLIS3	0	0
LINC02945	0	0
PAX6	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
KIF21A	4	Binding:3, Toxicity: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: 9; 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	1	IMMP1L
E	Difficult family or no structure, no drug	8	FOXC1, PITX2, ELP4, KIF21A, DCDC1, GLIS3, LINC02945, PAX6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FOXC1	0	—
PITX2	0	—
ELP4	0	—
KIF21A	4	—
DCDC1	0	—
IMMP1L	0	—
GLIS3	0	—
LINC02945	0	—
PAX6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	16
PHASE2	2
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02647359	PHASE2	COMPLETED	Study of Ataluren in Participants With Nonsense Mutation Aniridia
NCT04117880	PHASE2	WITHDRAWN	A Phase 2 Open Label Extension Study in Participants With Nonsense Mutation Aniridia
NCT05044598	PHASE1/PHASE2	COMPLETED	RAFT - Clinical Trial of RAFT for Aniridia Related Keratopathy
NCT05909735	PHASE1	COMPLETED	Treatment of LSCD With DM
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05390801	Not specified	RECRUITING	Congenital Aniridia Patient Questionnaire
NCT05400590	Not specified	RECRUITING	Comparison of the Healing Properties on Corneal Cells of Groth Factor-enriched Plasma and Autologous Serum From Aniridia Patients
NCT05954403	Not specified	RECRUITING	National Cohort on Congenital Defects of the Eye
NCT06491615	Not specified	RECRUITING	National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases
NCT00001161	Not specified	COMPLETED	Abnormalities of the Eye’s Anterior Chamber, Iris, Cornea and Lens
NCT00265590	Not specified	COMPLETED	Correlation of Gene Abnormalities and Clinical Manifestations of Aniridia
NCT00503893	Not specified	UNKNOWN	Genetics of Wilms’ Tumor and/or the Associated Conditions of Aniridia, Hemihypertrophy, and Genitourinary Anomalies
NCT00758108	Not specified	COMPLETED	Characterization of WAGR Syndrome and Other Chromosome 11 Gene Deletions
NCT00812708	Not specified	COMPLETED	Clinical Evaluation of Morcher Artificial Iris Diaphragms
NCT01644552	Not specified	COMPLETED	Positive Angle Kappa
NCT02945176	Not specified	COMPLETED	Safety and Performance Study of the ARGOS-IO System in Patients Undergoing Boston Keratoprosthesis Implantation
NCT03461978	Not specified	COMPLETED	Ultrahigh-resolution Optical Coherence Tomography Imaging of the Anterior Eye Segment Structures
NCT03581864	Not specified	COMPLETED	Clinical Outcomes of Implantationof Black Diaphragm Intraocular Lens in Complete Aniridia and Aphakia Due to Posttraumatic Eye Rupture
NCT05562115	Not specified	COMPLETED	Proteomic Study of Tears From Patients With a PAX6 Mutation
NCT06412718	Not specified	UNKNOWN	Validation of Human Drugs Target of Repurposed Drugs and Novel Therapies

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATALUREN	4	2