Coloboma of optic nerve

Summary

Coloboma of optic nerve (MONDO:0007354) is a disease with 4 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 4
• ClinVar variants: 15
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coloboma of optic nerve
Mondo ID	MONDO:0007354
MeSH	C535970
OMIM	120430
Orphanet	98947
DOID	DOID:11975
ICD-11	592278969
SNOMED CT	17541006
UMLS	C0155299
MedGen	57832
GARD	0001438
Is cancer (heuristic)	no

Also known as: coloboma of optic disc · coloboma of optic nerve (disease) · coloboma of optic papilla · congenital coloboma of the optic nerve · optic nerve coloboma

Data availability: 15 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › coloboma › coloboma of optic nerve

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

Subtypes (1): morning glory 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

15 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 benign/likely benign, 1 benign, 1 likely benign, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3474	NM_001368894.2(PAX6):c.1310A>T (p.Ter437Leu)	ELP4	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
3471	NM_001368894.2(PAX6):c.419T>A (p.Val140Asp)	PAX6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3475	NM_001368894.2(PAX6):c.244C>T (p.Pro82Ser)	PAX6	Pathogenic	no assertion criteria provided
2734044	NM_000488.4(SERPINC1):c.409-1G>T	SERPINC1	Pathogenic	criteria provided, multiple submitters, no conflicts
691929	NM_032656.4(DHX37):c.1145A>G (p.Asp382Gly)	DHX37	Likely pathogenic	no assertion criteria provided
638055	NM_001368894.2(PAX6):c.1303_1309del (p.Leu435fs)	ELP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
267835	46;XX;der(6)t(6;13)(q23.3;q22)inv(6)(p21.3q15);der(13)t(6;13)dn		Uncertain significance	criteria provided, single submitter
932051	NM_001368894.2(PAX6):c.1301G>A (p.Arg434Lys)	ELP4	Uncertain significance	criteria provided, single submitter
1034147	NM_001368894.2(PAX6):c.1198A>G (p.Met400Val)	PAX6	Uncertain significance	criteria provided, multiple submitters, no conflicts
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
1237893	NM_001368894.2(PAX6):c.*20_*21del (p.Ter437=)	ELP4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1262320	NM_001368894.2(PAX6):c.*21dup (p.Ter437=)	ELP4	Benign	criteria provided, multiple submitters, no conflicts
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: 17 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DHX37	Orphanet:242	46,XY complete gonadal dysgenesis
DHX37	Orphanet:251510	46,XY partial gonadal dysgenesis
DHX37	Orphanet:983	Testicular regression syndrome
SERPINC1	Orphanet:82	Hereditary thrombophilia due to congenital antithrombin deficiency
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

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ELP4	HGNC:1171	ENSG00000109911	Q96EB1	Elongator complex protein 4	clinvar
DHX37	HGNC:17210	ENSG00000150990	Q8IY37	Probable ATP-dependent RNA helicase DHX37	clinvar
SERPINC1	HGNC:775	ENSG00000117601	P01008	Antithrombin-III	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)
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).
DHX37	Probable ATP-dependent RNA helicase DHX37	ATP-binding RNA helicase that plays a role in maturation of the small ribosomal subunit in ribosome biogenesis.
SERPINC1	Antithrombin-III	Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade.
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: 3 · 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	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ELP4	Other/Unknown	no		Elongator_complex_protein_4, P-loop_NTPase
DHX37	Other/Unknown	no		Helicase_C-like, Helicase-assoc_dom, DEAD/DEAH_box_helicase_dom
SERPINC1	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
calcaneal tendon	1
primordial germ cell in gonad	1
medial globus pallidus	1
pancreatic ductal cell	1
tendon of biceps brachii	1
adrenal tissue	1
liver	1
right lobe of liver	1
palpebral conjunctiva	1
type B pancreatic cell	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
DHX37	236	ubiquitous	yes	pancreatic ductal cell, tendon of biceps brachii, medial globus pallidus
SERPINC1	153	tissue_specific	marker	right lobe of liver, liver, adrenal tissue
PAX6	201	broad	marker	palpebral conjunctiva, type B pancreatic cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971
DHX37	3,123
SERPINC1	1,833
ELP4	1,740

Intra-cohort edges

A	B	Sources
ELP4	PAX6	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SERPINC1	P01008	27
PAX6	P26367	2
DHX37	Q8IY37	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELP4	Q96EB1	74.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
R-HSA-140875	1	713.8×	0.015	SERPINC1
R-HSA-140837	1	356.9×	0.015	SERPINC1
Formation of the anterior neural plate	1	259.6×	0.015	PAX6
R-HSA-140877	1	237.9×	0.015	SERPINC1
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	219.6×	0.015	PAX6
Fibrin formation	1	219.6×	0.015	SERPINC1
Amplification and propagation of coagulation cascade	1	158.6×	0.017	SERPINC1
Regulation of gene expression in beta cells	1	129.8×	0.017	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	129.8×	0.017	PAX6
Initiation of coagulation cascade	1	119.0×	0.017	SERPINC1
Regulation of clotting cascade	1	58.3×	0.031	SERPINC1
rRNA modification in the nucleus and cytosol	1	46.8×	0.035	DHX37
Post-translational protein phosphorylation	1	25.0×	0.061	SERPINC1
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	22.8×	0.061	PAX6
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	21.6×	0.061	SERPINC1
HATs acetylate histones	1	19.8×	0.062	ELP4
Major pathway of rRNA processing in the nucleolus and cytosol	1	15.4×	0.074	DHX37
Hemostasis	1	9.0×	0.118	SERPINC1
Post-translational protein modification	1	4.8×	0.203	SERPINC1
Metabolism of proteins	1	3.1×	0.286	SERPINC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 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	4213.0×	0.004	PAX6
oligodendrocyte cell fate specification	1	4213.0×	0.004	PAX6
forebrain-midbrain boundary formation	1	4213.0×	0.004	PAX6
somatic motor neuron fate commitment	1	4213.0×	0.004	PAX6
habenula development	1	1404.3×	0.007	PAX6
regulation of asymmetric cell division	1	1053.2×	0.007	PAX6
regulation of timing of cell differentiation	1	1053.2×	0.007	PAX6
ventral spinal cord interneuron specification	1	702.2×	0.007	PAX6
commitment of neuronal cell to specific neuron type in forebrain	1	702.2×	0.007	PAX6
salivary gland morphogenesis	1	601.9×	0.007	PAX6
cerebral cortex regionalization	1	601.9×	0.007	PAX6
type B pancreatic cell differentiation	1	526.6×	0.007	PAX6
forebrain dorsal/ventral pattern formation	1	526.6×	0.007	PAX6
lacrimal gland development	1	526.6×	0.007	PAX6
ventral spinal cord development	1	468.1×	0.007	PAX6
regulation of blood coagulation	1	468.1×	0.007	SERPINC1
positive regulation of epithelial cell differentiation	1	468.1×	0.007	PAX6
ribosome assembly	1	468.1×	0.007	DHX37
iris morphogenesis	1	468.1×	0.007	PAX6
brain development	2	39.8×	0.007	DHX37, PAX6
positive regulation of male gonad development	1	421.3×	0.008	DHX37
dorsal/ventral axis specification	1	383.0×	0.008	PAX6
spinal cord motor neuron cell fate specification	1	383.0×	0.008	PAX6
cornea development in camera-type eye	1	324.1×	0.009	PAX6
tRNA wobble uridine modification	1	300.9×	0.009	ELP4
negative regulation of neuroblast proliferation	1	300.9×	0.009	PAX6
embryonic camera-type eye morphogenesis	1	280.9×	0.009	PAX6
cell fate determination	1	234.1×	0.011	PAX6
eye photoreceptor cell development	1	210.7×	0.011	PAX6
neuron fate commitment	1	200.6×	0.012	PAX6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SERPINC1	1	3
ELP4	0	0
DHX37	0	0
PAX6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IDRAPARINUX SODIUM	3	SERPINC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SERPINC1	19	Binding:19

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
IDRAPARINUX SODIUM	3	SERPINC1

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	1	SERPINC1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	ELP4, DHX37, PAX6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ELP4	0	—
DHX37	0	—
PAX6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02157025	Not specified	RECRUITING	A More Engaging Visual Field Test to Increase Use and Reliability in Pediatrics