Coloboma of superior eyelid

Summary

Coloboma of superior eyelid (MONDO:0015480) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coloboma of superior eyelid
Mondo ID	MONDO:0015480
Orphanet	155884
SNOMED CT	763132003
UMLS	C1863872
MedGen	350283
GARD	0019977
Is cancer (heuristic)	no

Also known as: superior palpebral coloboma

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › facial cleft › coloboma of superior eyelid

Related subtypes (8): bifid nose, commissural facial cleft, median cleft of the upper lip and maxilla, Tessier number 5 facial cleft, Tessier number 6 facial cleft, midline cervical cleft, coloboma of inferior eyelid, median cleft lip/mandibule

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065336	NM_001374353.1(GLI2):c.3784C>T (p.His1262Tyr)	GLI2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GLI2	Orphanet:220386	Semilobar holoprosencephaly
GLI2	Orphanet:280195	Septopreoptic holoprosencephaly
GLI2	Orphanet:280200	Microform holoprosencephaly
GLI2	Orphanet:420584	Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome
GLI2	Orphanet:93924	Lobar holoprosencephaly
GLI2	Orphanet:93925	Alobar holoprosencephaly
GLI2	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
GLI2	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms

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
GLI2	HGNC:4318	ENSG00000074047	P10070	Zinc finger protein GLI2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GLI2	Zinc finger protein GLI2	Functions as a transcription regulator in the hedgehog (Hh) pathway.

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)
GLI2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like

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
germinal epithelium of ovary	1
tibia	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GLI2	211	ubiquitous	marker	tibia, germinal epithelium of ovary, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GLI2	3,112

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GLI2	P10070	42.68

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
RUNX2 regulates chondrocyte maturation	1	2284.0×	0.002	GLI2
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	1631.4×	0.002	GLI2
Degradation of GLI2 by the proteasome	1	223.9×	0.006	GLI2
Hedgehog ‘off’ state	1	178.4×	0.006	GLI2
Hedgehog ‘on’ state	1	158.6×	0.006	GLI2

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
ventral midline development	1	5617.3×	0.002	GLI2
floor plate formation	1	5617.3×	0.002	GLI2
spinal cord ventral commissure morphogenesis	1	5617.3×	0.002	GLI2
hindgut morphogenesis	1	4213.0×	0.002	GLI2
tube development	1	4213.0×	0.002	GLI2
cerebellar cortex morphogenesis	1	2808.7×	0.002	GLI2
spinal cord dorsal/ventral patterning	1	2106.5×	0.002	GLI2
ventral spinal cord development	1	1872.4×	0.002	GLI2
epidermal cell differentiation	1	1685.2×	0.002	GLI2
positive regulation of T cell differentiation in thymus	1	1532.0×	0.002	GLI2
hindbrain development	1	1123.5×	0.003	GLI2
osteoblast development	1	991.3×	0.003	GLI2
embryonic digestive tract development	1	991.3×	0.003	GLI2
developmental growth	1	732.7×	0.003	GLI2
branching morphogenesis of an epithelial tube	1	732.7×	0.003	GLI2
proximal/distal pattern formation	1	648.1×	0.003	GLI2
pituitary gland development	1	648.1×	0.003	GLI2
mammary gland development	1	648.1×	0.003	GLI2
positive regulation of DNA replication	1	581.1×	0.003	GLI2
hair follicle morphogenesis	1	495.6×	0.004	GLI2
pattern specification process	1	468.1×	0.004	GLI2
odontogenesis of dentin-containing tooth	1	300.9×	0.005	GLI2
neuron development	1	255.3×	0.006	GLI2
cellular response to virus	1	200.6×	0.007	GLI2
lung development	1	198.3×	0.007	GLI2
smoothened signaling pathway	1	181.2×	0.008	GLI2
kidney development	1	140.4×	0.009	GLI2
skeletal system development	1	125.8×	0.010	GLI2
osteoblast differentiation	1	121.2×	0.010	GLI2
axon guidance	1	90.6×	0.013	GLI2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GLI2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GLI2	6	Binding:6

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	GLI2

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)
GLI2	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.