Juvenile open angle glaucoma

Summary

Juvenile open angle glaucoma (MONDO:0020367) is a disease (an umbrella term covering 6 Mondo subtypes) caused by variants in MYOC and EFEMP1, with 6 cohort genes and 1 clinical trial. The dominant Reactome pathway is Molecules associated with elastic fibres (3 cohort genes).

At a glance

• Prevalence: 1-9 / 100 000 (United States) [Orphanet-validated]
• Causal genes: MYOC (GenCC Definitive), EFEMP1 (GenCC Strong)
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 6
• ClinVar variants: 7
• Phenotypes (HPO): 15
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2	United States	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000525	Abnormality iris morphology	Frequent (30-79%)
HP:0000587	Abnormal optic nerve morphology	Frequent (30-79%)
HP:0000593	Abnormal anterior chamber morphology	Frequent (30-79%)
HP:0001138	Optic neuropathy	Frequent (30-79%)
HP:0007854	Glaucomatous visual field defect	Frequent (30-79%)
HP:0007906	Ocular hypertension	Frequent (30-79%)
HP:0007994	Peripheral visual field loss	Frequent (30-79%)
HP:0012108	Open angle glaucoma	Frequent (30-79%)
HP:0011003	High myopia	Occasional (5-29%)
HP:0012511	Temporal optic disc pallor	Occasional (5-29%)
HP:0012796	Increased cup-to-disc ratio	Occasional (5-29%)
HP:0000603	Central scotoma	Very rare (<1-4%)
HP:0012636	Retinal vein occlusion	Very rare (<1-4%)
HP:0025326	Retinal arterial occlusion	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile open angle glaucoma
Mondo ID	MONDO:0020367
Orphanet	98977
DOID	DOID:1068
SNOMED CT	71111008
UMLS	C2981140
MedGen	453382
GARD	0016883
MedDRA	10064032
Is cancer (heuristic)	no

Also known as: childhood glaucoma (disease) · glaucoma (disease) of childhood · glaucoma of childhood · JOAG · juvenile glaucoma · paediatric glaucoma (disease) · pediatric glaucoma (disease)

Data availability: 7 ClinVar variants · 6 ClinGen variant curations · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › glaucoma › open-angle glaucoma › juvenile open angle glaucoma

Related subtypes (6): residual stage of open angle glaucoma, low tension glaucoma, glaucoma 1, open angle, P, glaucoma type 1C, glaucoma 1, open angle, O, OPTN-related open angle glaucoma

Subtypes (6): glaucoma 1, open angle, A, glaucoma 1, open angle, J, glaucoma 1, open angle, K, glaucoma 1, open angle, M, glaucoma 1, open angle, N, glaucoma 1, open angle, l

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

7 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 likely pathogenic, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
7735	NM_000104.4(CYP1B1):c.1159G>A (p.Glu387Lys)	CYP1B1	Pathogenic	reviewed by expert panel
1294421	NM_001039348.3(EFEMP1):c.238A>T (p.Asn80Tyr)	EFEMP1	Pathogenic	no assertion criteria provided
1294422	NM_001039348.3(EFEMP1):c.1480T>C (p.Ter494Gln)	EFEMP1	Pathogenic	criteria provided, single submitter
973778	NM_001453.3(FOXC1):c.697del (p.Cys233fs)	FOXC1	Pathogenic	no assertion criteria provided
667380	NM_000428.3(LTBP2):c.4597C>T (p.Gln1533Ter)	LTBP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1294423	NM_001039348.3(EFEMP1):c.1429C>T (p.Arg477Cys)	EFEMP1	Likely pathogenic	no assertion criteria provided
267920	46;XY;t(6;20)(p12;q13.1)dn		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · Orphanet: 18 · 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
MYOC	Definitive	Autosomal dominant	glaucoma 1, open angle, A	7
EFEMP1	Strong	Autosomal dominant	juvenile open angle glaucoma	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EFEMP1	Orphanet:75376	Familial drusen
EFEMP1	Orphanet:98977	Juvenile glaucoma
MYOC	Orphanet:98976	Congenital glaucoma
MYOC	Orphanet:98977	Juvenile glaucoma
CYP1B1	Orphanet:708	Peters anomaly
CYP1B1	Orphanet:98976	Congenital glaucoma
CYP1B1	Orphanet:98977	Juvenile glaucoma
FOXC1	Orphanet:250923	Isolated aniridia
FOXC1	Orphanet:708	Peters anomaly
FOXC1	Orphanet:782	Axenfeld-Rieger syndrome
FOXC1	Orphanet:91483	Rieger anomaly
FOXC1	Orphanet:98978	Axenfeld anomaly
LTBP2	Orphanet:238763	Glaucoma secondary to spherophakia/ectopia lentis and megalocornea
LTBP2	Orphanet:3449	Weill-Marchesani syndrome
LTBP2	Orphanet:98976	Congenital glaucoma
LTBP3	Orphanet:2623	Geleophysic dysplasia
LTBP3	Orphanet:2899	Brachyolmia-amelogenesis imperfecta syndrome
LTBP3	Orphanet:969	Acromicric dysplasia

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	gencc,clinvar
MYOC	HGNC:7610	ENSG00000034971	Q99972	Myocilin	gencc
CYP1B1	HGNC:2597	ENSG00000138061	Q16678	Cytochrome P450 1B1	clinvar
FOXC1	HGNC:3800	ENSG00000054598	Q12948	Forkhead box protein C1	clinvar
LTBP2	HGNC:6715	ENSG00000119681	Q14767	Latent-transforming growth factor beta-binding protein 2	clinvar
LTBP3	HGNC:6716	ENSG00000168056	Q9NS15	Latent-transforming growth factor beta-binding protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.
MYOC	Myocilin	Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration.
CYP1B1	Cytochrome P450 1B1	A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins.
FOXC1	Forkhead box protein C1	DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development.
LTBP2	Latent-transforming growth factor beta-binding protein 2	May play an integral structural role in elastic-fiber architectural organization and/or assembly.
LTBP3	Latent-transforming growth factor beta-binding protein 3	Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Other/Unknown	5	1.5×	0.348
Transcription factor	1	1.4×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EFEMP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
MYOC	Other/Unknown	no		Olfac-like_dom, Olfactomedin-like_domain
CYP1B1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
FOXC1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
LTBP2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
LTBP3	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom

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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
descending thoracic aorta	3
thoracic aorta	3
ascending aorta	2
right coronary artery	1
calcaneal tendon	1
esophagogastric junction muscularis propria	1
mucosa of stomach	1
cartilage tissue	1
pericardium	1
synovial joint	1
parotid gland	1
trigeminal ganglion	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EFEMP1	286	ubiquitous	marker	right coronary artery, thoracic aorta, descending thoracic aorta
MYOC	201	tissue_specific	marker	calcaneal tendon, mucosa of stomach, esophagogastric junction muscularis propria
CYP1B1	285	ubiquitous	marker	pericardium, cartilage tissue, synovial joint
FOXC1	267	ubiquitous	marker	parotid gland, vena cava, trigeminal ganglion
LTBP2	276	ubiquitous	marker	descending thoracic aorta, thoracic aorta, ascending aorta
LTBP3	279	broad	marker	descending thoracic aorta, thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EFEMP1	2,988
FOXC1	2,896
CYP1B1	2,883
LTBP2	2,658
LTBP3	2,339
MYOC	1,272

Intra-cohort edges

A	B	Sources
CYP1B1	FOXC1	string_interaction
CYP1B1	LTBP2	string_interaction
CYP1B1	MYOC	string_interaction
EFEMP1	LTBP3	intact
FOXC1	MYOC	string_interaction
LTBP2	MYOC	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYOC	Q99972	24
CYP1B1	Q16678	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EFEMP1	Q12805	77.67
LTBP3	Q9NS15	64.21
LTBP2	Q14767	58.33
FOXC1	Q12948	56.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 6 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
Molecules associated with elastic fibres	3	185.2×	4e-06	EFEMP1, LTBP2, LTBP3
Elastic fibre formation	2	134.3×	4e-04	LTBP2, LTBP3
TGF-beta receptor signaling activates SMADs	2	130.5×	4e-04	LTBP2, LTBP3
Signaling by TGF-beta Receptor Complex	2	80.1×	8e-04	LTBP2, LTBP3
Defective CYP1B1 causes Glaucoma	1	2284.0×	0.001	CYP1B1
Signaling by TGFB family members	2	46.1×	0.002	LTBP2, LTBP3
Extracellular matrix organization	2	25.2×	0.004	LTBP2, LTBP3
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	285.5×	0.005	CYP1B1
Formation of intermediate mesoderm	1	285.5×	0.005	FOXC1
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	253.8×	0.005	CYP1B1
Formation of the ureteric bud	1	99.3×	0.012	FOXC1
Endogenous sterols	1	78.8×	0.014	CYP1B1
Signal Transduction	2	4.1×	0.079	LTBP2, LTBP3

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
negative regulation of chondrocyte differentiation	2	224.7×	0.004	EFEMP1, LTBP3
skeletal muscle hypertrophy	1	2808.7×	0.007	MYOC
benzene-containing compound metabolic process	1	2808.7×	0.007	CYP1B1
glomerular epithelium development	1	2808.7×	0.007	FOXC1
positive regulation of hematopoietic stem cell differentiation	1	2808.7×	0.007	FOXC1
camera-type eye development	2	119.5×	0.007	EFEMP1, FOXC1
collagen fibril organization	2	74.9×	0.007	CYP1B1, FOXC1
trabecular meshwork development	1	1404.3×	0.008	CYP1B1
apoptotic process involved in outflow tract morphogenesis	1	1404.3×	0.008	FOXC1
negative regulation of apoptotic process involved in outflow tract morphogenesis	1	1404.3×	0.008	FOXC1
positive regulation of core promoter binding	1	1404.3×	0.008	FOXC1
transforming growth factor beta receptor signaling pathway	2	53.0×	0.008	LTBP2, LTBP3
post-embryonic eye morphogenesis	1	936.2×	0.009	EFEMP1
negative regulation of lymphangiogenesis	1	936.2×	0.009	FOXC1
positive regulation of hematopoietic progenitor cell differentiation	1	936.2×	0.009	FOXC1
obsolete membrane lipid catabolic process	1	702.2×	0.011	CYP1B1
endothelial cell-cell adhesion	1	702.2×	0.011	CYP1B1
paraxial mesoderm formation	1	561.7×	0.012	FOXC1
steroid catabolic process	1	401.2×	0.012	CYP1B1
mesenchymal cell development	1	401.2×	0.012	FOXC1
glycosaminoglycan metabolic process	1	401.2×	0.012	FOXC1
clustering of voltage-gated sodium channels	1	401.2×	0.012	MYOC
retinal blood vessel morphogenesis	1	401.2×	0.012	CYP1B1
positive regulation of mesenchymal stem cell differentiation	1	401.2×	0.012	LTBP3
toxin metabolic process	1	351.1×	0.012	CYP1B1
lacrimal gland development	1	351.1×	0.012	FOXC1
maintenance of lens transparency	1	351.1×	0.012	FOXC1
regulation of organ growth	1	351.1×	0.012	FOXC1
lung saccule development	1	351.1×	0.012	LTBP3
positive regulation of mesenchymal stem cell proliferation	1	351.1×	0.012	LTBP3

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 2 of 6 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CYP1B1	PAZOPANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP1B1	22	4
EFEMP1	0	0
MYOC	0	0
FOXC1	0	0
LTBP2	0	0
LTBP3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PAZOPANIB	4	CYP1B1
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
RESVERATROL	3	CYP1B1
BERGAPTEN	3	CYP1B1
QUERCETIN	3	CYP1B1
CANNABINOL	3	CYP1B1
LUTEOLIN	2	CYP1B1
FORMONONETIN	2	CYP1B1
FLAVONE	2	CYP1B1
2-METHOXYESTRADIOL	2	CYP1B1
PINOCEMBRIN	2	CYP1B1
KHELLIN	2	CYP1B1
BAICALEIN	2	CYP1B1
PTEROSTILBENE	2	CYP1B1
KAEMPFEROL	1	CYP1B1
PLUMBAGIN	1	CYP1B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CYP1B1	408	ADMET:281, Binding:127
MYOC	4	Binding:4

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CYP1B1	408

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

22 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)
PAZOPANIB	4	CYP1B1
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
RESVERATROL	3	CYP1B1
BERGAPTEN	3	CYP1B1
QUERCETIN	3	CYP1B1
CANNABINOL	3	CYP1B1
LUTEOLIN	2	CYP1B1
FORMONONETIN	2	CYP1B1
FLAVONE	2	CYP1B1
2-METHOXYESTRADIOL	2	CYP1B1
PINOCEMBRIN	2	CYP1B1
KHELLIN	2	CYP1B1
BAICALEIN	2	CYP1B1
PTEROSTILBENE	2	CYP1B1
KAEMPFEROL	1	CYP1B1
PLUMBAGIN	1	CYP1B1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYP1B1
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	5	EFEMP1, MYOC, FOXC1, LTBP2, LTBP3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYOC	4	CYP1B1
FOXC1	0	CYP1B1
EFEMP1	0	—
LTBP2	0	—
LTBP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07396441	PHASE4	RECRUITING	Supplementary Kelulut Honey Therapy in Juvenile Open-Angle Glaucoma: Effects on IL-6, RNFL and Dry Eye