glaucoma 3, primary infantile, B

Summary

glaucoma 3, primary infantile, B (MONDO:0010968) is a disease with 4 cohort genes and 11 clinical trials.

At a glance

• Cohort genes: 4
• ClinVar variants: 61
• Clinical trials: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glaucoma 3, primary infantile, B
Mondo ID	MONDO:0010968
MeSH	C536824
OMIM	600975
UMLS	C1832977
MedGen	331409
GARD	0002490
Is cancer (heuristic)	no

Also known as: glaucoma 3 primary infantile B · glaucoma 3, primary infantile, B · glaucoma primary congenita type 3B · GLC3 type B · GLC3B · primary congenital glaucoma · primary congenital glaucoma type 3B

Data availability: 61 ClinVar variants · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary glaucoma › congenital glaucoma › glaucoma 3, primary infantile, B

Related subtypes (3): primary congenital glaucoma, glaucoma type 1C, glaucoma 3, primary congenital, E

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

61 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 15 conflicting classifications of pathogenicity, 7 likely pathogenic, 4 pathogenic, 4 benign, 3 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322184	NM_000104.4(CYP1B1):c.517G>T (p.Glu173Ter)	CYP1B1	Pathogenic	reviewed by expert panel
265390	NM_000104.4(CYP1B1):c.830del (p.Phe276_Leu277insTer)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523943	NM_000104.4(CYP1B1):c.535del (p.Ala179fs)	CYP1B1	Pathogenic	reviewed by expert panel
7730	NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)	CYP1B1	Pathogenic	reviewed by expert panel
7737	NM_000104.4(CYP1B1):c.171G>A (p.Trp57Ter)	CYP1B1	Pathogenic	reviewed by expert panel
2110814	NM_000428.3(LTBP2):c.3638dup (p.Thr1214fs)	LTBP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3780702	NM_000459.5(TEK):c.1552C>T (p.Gln518Ter)	TEK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1172842	NM_000104.4(CYP1B1):c.578C>T (p.Pro193Leu)	CYP1B1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210852	NM_000104.4(CYP1B1):c.1099dup (p.Asp367fs)	CYP1B1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3779556	NM_000104.4(CYP1B1):c.1022G>A (p.Trp341Ter)	CYP1B1	Likely pathogenic	criteria provided, single submitter
3779557	NM_000104.4(CYP1B1):c.608A>G (p.Asn203Ser)	CYP1B1	Likely pathogenic	criteria provided, single submitter
813355	NM_000104.4(CYP1B1):c.1536_1541del (p.Pro513_Lys514del)	CYP1B1	Likely pathogenic	reviewed by expert panel
1507148	NM_000428.3(LTBP2):c.2389-2A>G	LTBP2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3780703	NM_000459.5(TEK):c.578del (p.Tyr193fs)	TEK	Likely pathogenic	criteria provided, single submitter
1335386	NM_000104.4(CYP1B1):c.859G>A (p.Ala287Thr)	CYP1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1343424	NM_000104.4(CYP1B1):c.1033C>T (p.Leu345Phe)	CYP1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225333	NM_000104.4(CYP1B1):c.958G>T (p.Val320Leu)	CYP1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897191	NM_000104.4(CYP1B1):c.701C>T (p.Thr234Met)	CYP1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
898364	NM_000104.4(CYP1B1):c.592G>A (p.Val198Ile)	CYP1B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
126955	NM_000428.3(LTBP2):c.4250A>G (p.Gln1417Arg)	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1354646	NM_000428.3(LTBP2):c.654C>T (p.Cys218=)	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1380286	NM_000428.3(LTBP2):c.4620C>T (p.Gly1540=)	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
314295	NM_000428.3(LTBP2):c.2788+14G>A	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
314305	NM_000428.3(LTBP2):c.1796C>T (p.Pro599Leu)	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
314311	NM_000428.3(LTBP2):c.1301C>T (p.Pro434Leu)	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
595867	NM_000428.3(LTBP2):c.1686+3G>A	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
886736	NM_000428.3(LTBP2):c.2388+8C>T	LTBP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
366393	NM_000459.5(TEK):c.309A>C (p.Glu103Asp)	TEK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
914145	NM_000459.5(TEK):c.882G>C (p.Lys294Asn)	TEK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1329081	NM_000104.4(CYP1B1):c.431A>G (p.Gln144Arg)	CYP1B1	Uncertain significance	reviewed by expert panel

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
TEK	Orphanet:1059	Blue rubber bleb nevus
TEK	Orphanet:2451	Mucocutaneous venous malformations
TEK	Orphanet:714806	Multifocal sporadic venous malformation
TEK	Orphanet:98976	Congenital glaucoma
CYP1B1	Orphanet:708	Peters anomaly
CYP1B1	Orphanet:98976	Congenital glaucoma
CYP1B1	Orphanet:98977	Juvenile glaucoma
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

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TEK	HGNC:11724	ENSG00000120156	Q02763	Angiopoietin-1 receptor	clinvar
CYP1B1	HGNC:2597	ENSG00000138061	Q16678	Cytochrome P450 1B1	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)
TEK	Angiopoietin-1 receptor	Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskelet…
CYP1B1	Cytochrome P450 1B1	A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins.
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: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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
Kinase	1	6.9×	0.273
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TEK	Kinase	yes	2.7.10.1	Prot_kinase_dom, EGF, Ser-Thr/Tyr_kinase_cat_dom
CYP1B1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
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.

4 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
ascending aorta	2
descending thoracic aorta	2
thoracic aorta	2
diaphragm	1
right lung	1
visceral pleura	1
cartilage tissue	1
pericardium	1
synovial joint	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TEK	223	broad	marker	right lung, diaphragm, visceral pleura
CYP1B1	285	ubiquitous	marker	pericardium, cartilage tissue, synovial joint
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: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP1B1	2,883
TEK	2,762
LTBP2	2,658
LTBP3	2,339

Intra-cohort edges

A	B	Sources
CYP1B1	LTBP2	string_interaction
CYP1B1	TEK	intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TEK	Q02763	17
CYP1B1	Q16678	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LTBP3	Q9NS15	64.21
LTBP2	Q14767	58.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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
Elastic fibre formation	2	167.9×	3e-04	LTBP2, LTBP3
TGF-beta receptor signaling activates SMADs	2	163.1×	3e-04	LTBP2, LTBP3
Molecules associated with elastic fibres	2	154.3×	3e-04	LTBP2, LTBP3
Signaling by TGF-beta Receptor Complex	2	100.2×	6e-04	LTBP2, LTBP3
Defective CYP1B1 causes Glaucoma	1	2855.0×	0.001	CYP1B1
Signaling by TGFB family members	2	57.7×	0.001	LTBP2, LTBP3
Extracellular matrix organization	2	31.6×	0.004	LTBP2, LTBP3
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	356.9×	0.006	CYP1B1
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	317.2×	0.006	CYP1B1
Signal Transduction	3	7.6×	0.006	TEK, LTBP2, LTBP3
Tie2 Signaling	1	150.3×	0.010	TEK
Endogenous sterols	1	98.5×	0.014	CYP1B1
MAPK1/MAPK3 signaling	1	32.8×	0.039	TEK
MAPK family signaling cascades	1	25.7×	0.047	TEK
Cell surface interactions at the vascular wall	1	23.8×	0.047	TEK
RAF/MAP kinase cascade	1	15.3×	0.068	TEK
Hemostasis	1	9.0×	0.107	TEK

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
benzene-containing compound metabolic process	1	4213.0×	0.007	CYP1B1
trabecular meshwork development	1	2106.5×	0.007	CYP1B1
regulation of endothelial cell apoptotic process	1	2106.5×	0.007	TEK
transforming growth factor beta receptor signaling pathway	2	79.5×	0.007	LTBP2, LTBP3
positive regulation of angiogenesis	2	57.7×	0.007	TEK, CYP1B1
obsolete membrane lipid catabolic process	1	1053.2×	0.009	CYP1B1
endothelial cell-cell adhesion	1	1053.2×	0.009	CYP1B1
glomerulus vasculature development	1	1053.2×	0.009	TEK
regulation of establishment or maintenance of cell polarity	1	842.6×	0.009	TEK
Tie signaling pathway	1	842.6×	0.009	TEK
steroid catabolic process	1	601.9×	0.009	CYP1B1
retinal blood vessel morphogenesis	1	601.9×	0.009	CYP1B1
positive regulation of mesenchymal stem cell differentiation	1	601.9×	0.009	LTBP3
toxin metabolic process	1	526.6×	0.009	CYP1B1
lung saccule development	1	526.6×	0.009	LTBP3
positive regulation of mesenchymal stem cell proliferation	1	526.6×	0.009	LTBP3
angiogenesis	2	31.2×	0.009	TEK, CYP1B1
omega-hydroxylase P450 pathway	1	383.0×	0.011	CYP1B1
blood vessel endothelial cell migration	1	351.1×	0.012	CYP1B1
negative regulation of cell adhesion mediated by integrin	1	324.1×	0.012	CYP1B1
regulation of vascular permeability	1	280.9×	0.012	TEK
heart trabecula formation	1	280.9×	0.012	TEK
supramolecular fiber organization	1	263.3×	0.012	LTBP2
positive regulation of bone resorption	1	247.8×	0.012	LTBP3
negative regulation of bone mineralization	1	234.1×	0.012	LTBP3
retinal metabolic process	1	234.1×	0.012	CYP1B1
bone remodeling	1	234.1×	0.012	LTBP3
definitive hemopoiesis	1	234.1×	0.012	TEK
epoxygenase P450 pathway	1	221.7×	0.012	CYP1B1
intrinsic apoptotic signaling pathway in response to oxidative stress	1	210.7×	0.012	CYP1B1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
TEK	CETIRIZINE
CYP1B1	PAZOPANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TEK	46	4
CYP1B1	22	4
LTBP2	0	0
LTBP3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CETIRIZINE	4	TEK
FEDRATINIB	4	TEK
TIVOZANIB	4	TEK
AXITINIB	4	TEK
SORAFENIB	4	TEK
NICLOSAMIDE	4	TEK
AMPICILLIN	4	TEK
NERATINIB	4	TEK
INFIGRATINIB PHOSPHATE	4	TEK
INFIGRATINIB	4	TEK
REGORAFENIB	4	TEK
CABOZANTINIB	4	TEK
VANDETANIB	4	TEK
NILOTINIB	4	TEK
BOSUTINIB	4	TEK
PAZOPANIB	4	CYP1B1, TEK
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
LINIFANIB	3	TEK
BRIVANIB	3	TEK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TEK	707	Binding:701, Functional:4, ADMET:2
CYP1B1	408	ADMET:281, Binding:127

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TEK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TEK	707
CYP1B1	408

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

30 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)
CETIRIZINE	4	TEK
FEDRATINIB	4	TEK
TIVOZANIB	4	TEK
AXITINIB	4	TEK
SORAFENIB	4	TEK
NICLOSAMIDE	4	TEK
AMPICILLIN	4	TEK
NERATINIB	4	TEK
INFIGRATINIB PHOSPHATE	4	TEK
INFIGRATINIB	4	TEK
REGORAFENIB	4	TEK
CABOZANTINIB	4	TEK
VANDETANIB	4	TEK
NILOTINIB	4	TEK
BOSUTINIB	4	TEK
PAZOPANIB	4	CYP1B1, TEK
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
LINIFANIB	3	TEK
BRIVANIB	3	TEK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TEK, 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	2	LTBP2, LTBP3

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)
LTBP2	0	—
LTBP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07550868	Not specified	NOT_YET_RECRUITING	Goniotomy in Primary Congenital Glaucoma
NCT01020721	Not specified	UNKNOWN	The Genetic Characteristics in South Korean Patients With Primary Congenital Glaucoma
NCT03541551	Not specified	COMPLETED	Ologen® Collagen Matrix in Patients With Primary Congenital Glaucoma Undergoing Trabeculectomy
NCT04079725	Not specified	UNKNOWN	Iris Tissue in Primary Congenital Glaucoma
NCT04116450	Not specified	COMPLETED	MicrocatheterTrabeculotomy in Primary Congenital Glaucoma
NCT04647929	Not specified	WITHDRAWN	Comparison of Surgical Treatment Options for Primary Congenital and Developmental Glaucomas
NCT04683289	Not specified	COMPLETED	Visco-Circumferential-Suture-Trabeculotomy Versus Trabeculotomy
NCT04709497	Not specified	UNKNOWN	Surgery for Primary Congenital Glaucoma in Neonates
NCT04949555	Not specified	UNKNOWN	Long Term Evaluation of Primary Congenital Glaucoma Management in Sohag University Hospital
NCT05205122	Not specified	UNKNOWN	Evaluation of Primary Congenital Glaucoma at Asyut University Hospital
NCT07012252	Not specified	COMPLETED	Optical Coherence Tomography of the Irido-Corneal Angle Before and After Goniotomy and Trabeculotomy in Primary Congenital Glaucoma