Coloboma, ocular, autosomal dominant

Summary

Coloboma, ocular, autosomal dominant (MONDO:0007350) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coloboma, ocular, autosomal dominant
Mondo ID	MONDO:0007350
OMIM	120200
UMLS	C5886785
MedGen	1859952
Is cancer (heuristic)	no

Also known as: coloboma, ocular · coloboma, ocular, autosomal dominant

Data availability: 19 ClinVar variants.

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 › coloboma › coloboma, ocular, autosomal dominant

Related subtypes (7): microphthalmia, isolated, with coloboma, coloboma of macula, coloboma of optic nerve, coloboma, ocular, autosomal recessive, coloboma of eye lens, coloboma of eyelid, calloso-genital dysplasia

Subtypes (2): coloboma of choroid and retina, coloboma of iris

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

19 retrieved; paginated sample, class counts are floors:

7 pathogenic, 5 pathogenic/likely pathogenic, 4 uncertain significance, 1 likely benign, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2152105	NM_001368894.2(PAX6):c.113G>A (p.Arg38Gln)	PAX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279862	NM_001368894.2(PAX6):c.823C>T (p.Arg275Ter)	PAX6	Pathogenic	criteria provided, multiple submitters, no conflicts
289849	NM_001368894.2(PAX6):c.52G>C (p.Gly18Arg)	PAX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3024448	NM_001368894.2(PAX6):c.809T>C (p.Val270Ala)	PAX6	Pathogenic	no assertion criteria provided
3024449	NM_001368894.2(PAX6):c.414C>A (p.Asn138Lys)	PAX6	Pathogenic	no assertion criteria provided
3024450	NM_001368894.2(PAX6):c.414C>G (p.Asn138Lys)	PAX6	Pathogenic	no assertion criteria provided
3024451	NM_001368894.2(PAX6):c.202A>C (p.Ser68Arg)	PAX6	Pathogenic	no assertion criteria provided
3024452	NM_001368894.2(PAX6):c.204T>G (p.Ser68Arg)	PAX6	Pathogenic	no assertion criteria provided
3463	NM_001368894.2(PAX6):c.76C>G (p.Arg26Gly)	PAX6	Pathogenic/Likely pathogenic	no assertion criteria provided
3471	NM_001368894.2(PAX6):c.419T>A (p.Val140Asp)	PAX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3477	NM_001368894.2(PAX6):c.815T>C (p.Phe272Ser)	PAX6	Pathogenic	no assertion criteria provided
40090	NM_001368894.2(PAX6):c.112C>T (p.Arg38Trp)	PAX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3024454	NM_001368894.2(PAX6):c.77G>A (p.Arg26Gln)	PAX6	Likely pathogenic	criteria provided, single submitter
800413	NM_001368894.2(PAX6):c.256G>C (p.Gly86Arg)	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1048792	NM_001368894.2(PAX6):c.1074+139C>T	PAX6	Uncertain significance	criteria provided, single submitter
1385887	NM_001368894.2(PAX6):c.556_564del (p.Pro186_Gln188del)	PAX6	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382303	NM_001368894.2(PAX6):c.535G>T (p.Gly179Trp)	PAX6	Uncertain significance	criteria provided, single submitter
4819927	NM_001368894.2(PAX6):c.770T>C (p.Leu257Pro)	PAX6	Uncertain significance	criteria provided, single submitter
1652503	NM_001368894.2(PAX6):c.1221A>C (p.Ser407=)	PAX6	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
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: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf

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
palpebral conjunctiva	1
type B pancreatic cell	1
ventricular zone	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PAX6	P26367	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Formation of the anterior neural plate	1	1038.2×	0.002	PAX6
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	878.5×	0.002	PAX6
Regulation of gene expression in beta cells	1	519.1×	0.002	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	519.1×	0.002	PAX6
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	91.4×	0.011	PAX6

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
pancreatic A cell development	1	16852.0×	9e-04	PAX6
oligodendrocyte cell fate specification	1	16852.0×	9e-04	PAX6
forebrain-midbrain boundary formation	1	16852.0×	9e-04	PAX6
somatic motor neuron fate commitment	1	16852.0×	9e-04	PAX6
habenula development	1	5617.3×	0.002	PAX6
regulation of asymmetric cell division	1	4213.0×	0.002	PAX6
regulation of timing of cell differentiation	1	4213.0×	0.002	PAX6
ventral spinal cord interneuron specification	1	2808.7×	0.002	PAX6
commitment of neuronal cell to specific neuron type in forebrain	1	2808.7×	0.002	PAX6
salivary gland morphogenesis	1	2407.4×	0.002	PAX6
cerebral cortex regionalization	1	2407.4×	0.002	PAX6
type B pancreatic cell differentiation	1	2106.5×	0.002	PAX6
forebrain dorsal/ventral pattern formation	1	2106.5×	0.002	PAX6
lacrimal gland development	1	2106.5×	0.002	PAX6
ventral spinal cord development	1	1872.4×	0.002	PAX6
positive regulation of epithelial cell differentiation	1	1872.4×	0.002	PAX6
iris morphogenesis	1	1872.4×	0.002	PAX6
dorsal/ventral axis specification	1	1532.0×	0.002	PAX6
spinal cord motor neuron cell fate specification	1	1532.0×	0.002	PAX6
cornea development in camera-type eye	1	1296.3×	0.002	PAX6
negative regulation of neuroblast proliferation	1	1203.7×	0.002	PAX6
embryonic camera-type eye morphogenesis	1	1123.5×	0.002	PAX6
cell fate determination	1	936.2×	0.003	PAX6
eye photoreceptor cell development	1	842.6×	0.003	PAX6
neuron fate commitment	1	802.5×	0.003	PAX6
astrocyte differentiation	1	766.0×	0.003	PAX6
signal transduction involved in regulation of gene expression	1	702.2×	0.003	PAX6
sensory organ development	1	674.1×	0.003	PAX6
pituitary gland development	1	648.1×	0.003	PAX6
negative regulation of neurogenesis	1	624.1×	0.003	PAX6

Therapeutics

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
PAX6	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	PAX6

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)
PAX6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.