Aniridia 1

Summary

Aniridia 1 (MONDO:0024507) is a disease caused by PAX6 (GenCC Definitive), with 7 cohort genes and 20 clinical trials. Top therapeutic interventions include ataluren.

At a glance

• Causal gene: PAX6 (GenCC Definitive)
• Cohort genes: 7
• ClinVar variants: 758
• Clinical trials: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aniridia 1
Mondo ID	MONDO:0024507
OMIM	106210
DOID	DOID:0070532
SNOMED CT	253231007
UMLS	C0344542
MedGen	576337
GARD	0025407
Is cancer (heuristic)	no

Also known as: AN1 · aniridia · aniridia 1 · cataract with late-onset corneal dystrophy

Data availability: 758 ClinVar variants · 4 GenCC gene-disease records · 16 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › isolated aniridia › aniridia 1

Related subtypes (2): aniridia 2, aniridia 3

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

600 retrieved; paginated sample, class counts are floors:

194 pathogenic, 140 likely benign, 134 uncertain significance, 42 likely pathogenic, 42 conflicting classifications of pathogenicity, 21 benign, 17 pathogenic/likely pathogenic, 9 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
376757	GRCh37/hg19 11p15.1-13(chr11:18536224-31923308)x1	ANO3	Pathogenic	no assertion criteria provided
376752	GRCh37/hg19 11p13(chr11:31147306-31714853)x1	DCDC1	Pathogenic	no assertion criteria provided
376754	GRCh37/hg19 11p13(chr11:31186493-31698208)x1	DCDC1	Pathogenic	no assertion criteria provided
376758	GRCh37/hg19 11p13(chr11:31083877-31704548)x1	DCDC1	Pathogenic	no assertion criteria provided
1072681	NC_000011.9:g.(?31284590)(31824402_?)del	DNAJC24	Pathogenic	criteria provided, single submitter
647471	NC_000011.9:g.(?31284590)(31832374_?)del	DNAJC24	Pathogenic	criteria provided, single submitter
120328	NM_019040.5(ELP4):c.1143+14176C>A	ELP4	Pathogenic	no assertion criteria provided
1458968	NC_000011.9:g.(?31804921)(31812428_?)del	ELP4	Pathogenic	criteria provided, single submitter
2422793	NC_000011.9:g.(?31625295)(31822424_?)del	ELP4	Pathogenic	criteria provided, single submitter
2422796	NC_000011.9:g.(?31804921)(31816356_?)del	ELP4	Pathogenic	criteria provided, single submitter
2443076	NM_001368894.2(PAX6):c.1277_1284dup (p.Ser429fs)	ELP4	Pathogenic	criteria provided, single submitter
3474	NM_001368894.2(PAX6):c.1310A>T (p.Ter437Leu)	ELP4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372441	NM_001368894.2(PAX6):c.664C>T (p.Arg222Trp)	ELP4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
376756	GRCh37/hg19 11p13(chr11:31760458-31823847)x1	ELP4	Pathogenic	no assertion criteria provided
529895	NC_000011.10:g.(?31789934)(31806411_?)del	ELP4	Pathogenic	criteria provided, single submitter
583750	NC_000011.9:g.(?31284590)(32456911_?)del	ELP4	Pathogenic	criteria provided, single submitter
584225	NC_000011.10:g.(?31664397)(31794829_?)del	ELP4-AS1	Pathogenic	criteria provided, single submitter
1023138	NM_001368894.2(PAX6):c.275T>A (p.Val92Glu)	PAX6	Pathogenic	criteria provided, multiple submitters, no conflicts
1069925	NM_001368894.2(PAX6):c.790_806del (p.Pro264fs)	PAX6	Pathogenic	criteria provided, single submitter
1070548	NM_001368894.2(PAX6):c.483del (p.Met162fs)	PAX6	Pathogenic	criteria provided, single submitter
1072682	NC_000011.9:g.(?31804921)(31816377_?)del	PAX6	Pathogenic	criteria provided, single submitter
1075087	NM_001368894.2(PAX6):c.720del (p.Glu242fs)	PAX6	Pathogenic	criteria provided, single submitter
1075401	NM_001368894.2(PAX6):c.52G>A (p.Gly18Arg)	PAX6	Pathogenic	criteria provided, single submitter
1254586	NM_001368894.2(PAX6):c.1090C>T (p.Gln364Ter)	PAX6	Pathogenic	criteria provided, multiple submitters, no conflicts
1328482	NM_001368894.2(PAX6):c.956del (p.Pro319fs)	PAX6	Pathogenic	criteria provided, single submitter
1372939	NM_001368894.2(PAX6):c.829del (p.Ala277fs)	PAX6	Pathogenic	criteria provided, single submitter
1389199	NM_001368894.2(PAX6):c.1061del (p.Asn354fs)	PAX6	Pathogenic	criteria provided, single submitter
1390086	NM_001368894.2(PAX6):c.1086del (p.Ser363fs)	PAX6	Pathogenic	criteria provided, single submitter
1429880	NM_001368894.2(PAX6):c.385_386dup (p.Asp129fs)	PAX6	Pathogenic	criteria provided, single submitter
1434624	NM_001368894.2(PAX6):c.399+2T>C	PAX6	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 23 · 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
PAX6	Definitive	Autosomal dominant	aniridia 1	14
ELP4	Strong	Autosomal dominant	aniridia 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
WT1	Orphanet:220	Denys-Drash syndrome
WT1	Orphanet:242	46,XY complete gonadal dysgenesis
WT1	Orphanet:251510	46,XY partial gonadal dysgenesis
WT1	Orphanet:3097	Meacham syndrome
WT1	Orphanet:347	Frasier syndrome
WT1	Orphanet:654	Nephroblastoma
WT1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
WT1	Orphanet:83469	Desmoplastic small round cell tumor
WT1	Orphanet:893	WAGR syndrome
ANO3	Orphanet:420485	Cranio-cervical dystonia with laryngeal and upper-limb involvement

Cohort genes → proteins

7 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	gencc,clinvar
PAX6	HGNC:8620	ENSG00000007372	P26367	Paired box protein Pax-6	gencc,clinvar
WT1	HGNC:12796	ENSG00000184937	P19544	Wilms tumor protein	clinvar
ANO3	HGNC:14004	ENSG00000134343	Q9BYT9	Anoctamin-3	clinvar
DCDC1	HGNC:20625	ENSG00000170959	M0R2J8	Doublecortin domain-containing protein 1	clinvar
DNAJC24	HGNC:26979	ENSG00000170946	Q6P3W2	DnaJ homolog subfamily C member 24	clinvar
ELP4-AS1	HGNC:58222	ENSG00000228061		ELP4 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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).
PAX6	Paired box protein Pax-6	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas.
WT1	Wilms tumor protein	Transcription factor that plays an important role in cellular development and cell survival.
ANO3	Anoctamin-3	Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylcholine and galactosylceramide.
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.
DNAJC24	DnaJ homolog subfamily C member 24	Stimulates the ATPase activity of several Hsp70-type chaperones.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 5 · 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	2	2.4×	0.332
Other/Unknown	5	1.3×	0.332

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf
WT1	Transcription factor	no		Wilms_tumour_N, Znf_C2H2_type, Znf_C2H2_sf
ANO3	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
DCDC1	Other/Unknown	no		Doublecortin_dom, Ricin_B-like_lectins, Doublecortin_dom_sf
DNAJC24	Other/Unknown	no		DnaJ_domain, DPH_MB_dom, DPH_MB_sf
ELP4-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

6 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	3
male germ line stem cell (sensu Vertebrata) in testis	2
calcaneal tendon	1
primordial germ cell in gonad	1
palpebral conjunctiva	1
type B pancreatic cell	1
germinal epithelium of ovary	1
metanephric glomerulus	1
renal glomerulus	1
corpus epididymis	1
lateral globus pallidus	1
putamen	1
oviduct epithelium	1
right uterine tube	1
Brodmann (1909) area 23	1
endothelial cell	1
heart right ventricle	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad
PAX6	201	broad	marker	palpebral conjunctiva, type B pancreatic cell, ventricular zone
WT1	168	broad	marker	germinal epithelium of ovary, renal glomerulus, metanephric glomerulus
ANO3	189	broad	marker	corpus epididymis, lateral globus pallidus, putamen
DCDC1	148	broad	marker	oviduct epithelium, right uterine tube, male germ line stem cell (sensu Vertebrata) in testis
DNAJC24	288	ubiquitous	marker	heart right ventricle, endothelial cell, Brodmann (1909) area 23
ELP4-AS1	124		yes	ventricular zone, ganglionic eminence, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971
WT1	3,938
DNAJC24	2,259
ELP4	1,740
ANO3	1,078
DCDC1	3
ELP4-AS1	0

Intra-cohort edges

A	B	Sources
DNAJC24	ELP4	string_interaction
DNAJC24	PAX6	string_interaction
ELP4	PAX6	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
WT1	P19544	28
PAX6	P26367	2
DNAJC24	Q6P3W2	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANO3	Q9BYT9	76.30
ELP4	Q96EB1	74.49
DCDC1	M0R2J8	68.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of diphthamide-EEF2	1	285.5×	0.023	DNAJC24
Formation of the anterior neural plate	1	207.6×	0.023	PAX6
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	175.7×	0.023	PAX6
Induction of Cell-Cell Fusion	1	175.7×	0.023	ANO3
Nephron development	1	175.7×	0.023	WT1
Transcriptional regulation of testis differentiation	1	142.8×	0.023	WT1
Regulation of gene expression in beta cells	1	103.8×	0.024	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	103.8×	0.024	PAX6
Late SARS-CoV-2 Infection Events	1	58.6×	0.038	ANO3
Stimuli-sensing channels	1	27.2×	0.072	ANO3
Negative Regulation of CDH1 Gene Transcription	1	24.0×	0.074	WT1
Ion channel transport	1	19.2×	0.082	ANO3
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	18.3×	0.082	PAX6
SARS-CoV-2 Infection	1	16.1×	0.082	ANO3
HATs acetylate histones	1	15.9×	0.082	ELP4
SARS-CoV Infections	1	11.1×	0.109	ANO3
Viral Infection Pathways	1	6.2×	0.179	ANO3
Transport of small molecules	1	5.0×	0.196	ANO3
Infectious disease	1	5.0×	0.196	ANO3
Disease	1	2.6×	0.328	ANO3

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
pancreatic A cell development	1	2808.7×	0.007	PAX6
oligodendrocyte cell fate specification	1	2808.7×	0.007	PAX6
forebrain-midbrain boundary formation	1	2808.7×	0.007	PAX6
somatic motor neuron fate commitment	1	2808.7×	0.007	PAX6
negative regulation of metanephric glomerular mesangial cell proliferation	1	2808.7×	0.007	WT1
positive regulation of miRNA transcription	2	96.8×	0.007	PAX6, WT1
regulation of animal organ formation	1	1404.3×	0.008	WT1
adrenal cortex formation	1	1404.3×	0.008	WT1
visceral serous pericardium development	1	1404.3×	0.008	WT1
posterior mesonephric tubule development	1	1404.3×	0.008	WT1
positive regulation of metanephric ureteric bud development	1	1404.3×	0.008	WT1
detection of temperature stimulus	1	936.2×	0.009	ANO3
habenula development	1	936.2×	0.009	PAX6
calcium activated galactosylceramide scrambling	1	936.2×	0.009	ANO3
regulation of mitotic cytokinesis	1	936.2×	0.009	DCDC1
regulation of asymmetric cell division	1	702.2×	0.009	PAX6
regulation of timing of cell differentiation	1	702.2×	0.009	PAX6
positive regulation of heart growth	1	702.2×	0.009	WT1
metanephric S-shaped body morphogenesis	1	702.2×	0.009	WT1
negative regulation of female gonad development	1	702.2×	0.009	WT1
thorax and anterior abdomen determination	1	561.7×	0.009	WT1
cardiac muscle cell fate commitment	1	561.7×	0.009	WT1
calcium activated phosphatidylcholine scrambling	1	561.7×	0.009	ANO3
metanephric epithelium development	1	561.7×	0.009	WT1
ventral spinal cord interneuron specification	1	468.1×	0.009	PAX6
commitment of neuronal cell to specific neuron type in forebrain	1	468.1×	0.009	PAX6
cellular response to gonadotropin stimulus	1	468.1×	0.009	WT1
salivary gland morphogenesis	1	401.2×	0.010	PAX6
protein histidyl modification to diphthamide	1	401.2×	0.010	DNAJC24
cerebral cortex regionalization	1	401.2×	0.010	PAX6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 7

Druggability breadth: 1 of 7 evidence-associated genes (14%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ELP4	0	0
PAX6	0	0
WT1	0	0
ANO3	0	0
DCDC1	0	0
DNAJC24	0	0
ELP4-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; 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	7	ELP4, PAX6, WT1, ANO3, DCDC1, DNAJC24, ELP4-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ELP4	0	—
PAX6	0	—
WT1	0	—
ANO3	0	—
DCDC1	0	—
DNAJC24	0	—
ELP4-AS1	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