PAX6-related ocular dysgenesis

Summary

PAX6-related ocular dysgenesis (MONDO:0800183) is a disease caused by PAX6 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PAX6 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	PAX6-related ocular dysgenesis
Mondo ID	MONDO:0800183
GARD	0026474
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › head and neck carcinoma › eye carcinoma › PAX6-related ocular dysgenesis

Related subtypes (8): cornea squamous cell carcinoma, lacrimal gland carcinoma, eyelid carcinoma, eye carcinoma in situ, conjunctival squamous cell carcinoma, ocular sebaceous carcinoma, aniridia 2, aniridia 3

Subtypes (2): foveal hypoplasia 1, isolated optic nerve hypoplasia

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

5 retrieved; paginated sample, class counts are floors:

1 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4070940	Single allele	ELP4	Pathogenic	criteria provided, single submitter
3471	NM_001368894.2(PAX6):c.419T>A (p.Val140Asp)	PAX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1710344	NM_001368894.2(PAX6):c.142-3T>C	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1237893	NM_001368894.2(PAX6):c.*20_*21del (p.Ter437=)	ELP4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
3780102	NM_001368894.2(PAX6):c.*19_*21del (p.Ter437=)	ELP4	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 13 · 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	Strong	Autosomal dominant	PAX6-related ocular dysgenesis	14

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

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
PAX6	HGNC:8620	ENSG00000007372	P26367	Paired box protein Pax-6	gencc,clinvar
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PAX6	Paired box protein Pax-6	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas.
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).

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)
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase

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
ventricular zone	2
palpebral conjunctiva	1
type B pancreatic cell	1
calcaneal tendon	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PAX6	201	broad	marker	palpebral conjunctiva, type B pancreatic cell, ventricular zone
ELP4	250	ubiquitous	marker	ventricular zone, calcaneal tendon, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971
ELP4	1,740

Intra-cohort edges

A	B	Sources
ELP4	PAX6	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PAX6	P26367	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELP4	Q96EB1	74.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Formation of the anterior neural plate	1	519.1×	0.006	PAX6
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	439.2×	0.006	PAX6
Regulation of gene expression in beta cells	1	259.6×	0.006	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	259.6×	0.006	PAX6
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	45.7×	0.025	PAX6
HATs acetylate histones	1	39.6×	0.025	ELP4

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
pancreatic A cell development	1	8426.0×	0.002	PAX6
oligodendrocyte cell fate specification	1	8426.0×	0.002	PAX6
forebrain-midbrain boundary formation	1	8426.0×	0.002	PAX6
somatic motor neuron fate commitment	1	8426.0×	0.002	PAX6
habenula development	1	2808.7×	0.004	PAX6
regulation of asymmetric cell division	1	2106.5×	0.004	PAX6
regulation of timing of cell differentiation	1	2106.5×	0.004	PAX6
ventral spinal cord interneuron specification	1	1404.3×	0.004	PAX6
commitment of neuronal cell to specific neuron type in forebrain	1	1404.3×	0.004	PAX6
salivary gland morphogenesis	1	1203.7×	0.004	PAX6
cerebral cortex regionalization	1	1203.7×	0.004	PAX6
type B pancreatic cell differentiation	1	1053.2×	0.004	PAX6
forebrain dorsal/ventral pattern formation	1	1053.2×	0.004	PAX6
lacrimal gland development	1	1053.2×	0.004	PAX6
ventral spinal cord development	1	936.2×	0.004	PAX6
positive regulation of epithelial cell differentiation	1	936.2×	0.004	PAX6
iris morphogenesis	1	936.2×	0.004	PAX6
dorsal/ventral axis specification	1	766.0×	0.004	PAX6
spinal cord motor neuron cell fate specification	1	766.0×	0.004	PAX6
cornea development in camera-type eye	1	648.1×	0.005	PAX6
tRNA wobble uridine modification	1	601.9×	0.005	ELP4
negative regulation of neuroblast proliferation	1	601.9×	0.005	PAX6
embryonic camera-type eye morphogenesis	1	561.7×	0.005	PAX6
cell fate determination	1	468.1×	0.006	PAX6
eye photoreceptor cell development	1	421.3×	0.006	PAX6
neuron fate commitment	1	401.2×	0.006	PAX6
astrocyte differentiation	1	383.0×	0.006	PAX6
signal transduction involved in regulation of gene expression	1	351.1×	0.006	PAX6
sensory organ development	1	337.0×	0.006	PAX6
pituitary gland development	1	324.1×	0.006	PAX6

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
PAX6	0	0
ELP4	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	PAX6, ELP4

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)
PAX6	0	—
ELP4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.