Primary congenital glaucoma

Summary

Primary congenital glaucoma (MONDO:0000365) is a disease caused by TEK (GenCC Definitive), with 2 cohort genes and 11 clinical trials.

At a glance

• Causal gene: TEK (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 35
• Clinical trials: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary congenital glaucoma
Mondo ID	MONDO:0000365
DOID	DOID:0050593
ICD-11	517092878
NCIT	C150251
SNOMED CT	415176004
UMLS	C1533041
MedGen	288550
GARD	0022755
Is cancer (heuristic)	no

Also known as: primary congenital glaucoma · primary congenital glaucoma (disease)

Data availability: 35 ClinVar variants · 1 GenCC gene-disease record · 1 HPO phenotype · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

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

Subtypes (3): glaucoma 3, primary congenital, C, glaucoma 3, primary congenital, D, CYP1B1-related glaucoma with or without anterior segment dysgenesis

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

35 retrieved; paginated sample, class counts are floors:

17 pathogenic, 10 likely pathogenic, 5 pathogenic/likely pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1203967	NM_000104.4(CYP1B1):c.1A>G (p.Met1Val)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324202	NM_000104.4(CYP1B1):c.1390dup (p.Ser464fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1339668	NM_000104.4(CYP1B1):c.1090G>A (p.Val364Met)	CYP1B1	Pathogenic	reviewed by expert panel
1339669	NM_000104.4(CYP1B1):c.970_971dup (p.Thr325fs)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
1412564	NM_000104.4(CYP1B1):c.1063C>T (p.Arg355Ter)	CYP1B1	Pathogenic	reviewed by expert panel
2203048	NM_000104.4(CYP1B1):c.1168C>A (p.Arg390Ser)	CYP1B1	Pathogenic	reviewed by expert panel
2203049	NM_000104.4(CYP1B1):c.988_989delinsTT (p.Ala330Phe)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2577219	NM_000104.4(CYP1B1):c.317C>A (p.Ala106Asp)	CYP1B1	Pathogenic	reviewed by expert panel
2637448	NM_000104.4(CYP1B1):c.277_306delinsGG (p.Pro93fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681130	NM_000104.4(CYP1B1):c.872A>G (p.Asp291Gly)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
282564	NM_000104.4(CYP1B1):c.1064_1076del (p.Arg355fs)	CYP1B1	Pathogenic	reviewed by expert panel
3236697	NM_000104.4(CYP1B1):c.1333T>A (p.Phe445Ile)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
335952	NM_000104.4(CYP1B1):c.1168C>T (p.Arg390Cys)	CYP1B1	Pathogenic	reviewed by expert panel
4530672	NM_000104.4(CYP1B1):c.1568G>C (p.Arg523Thr)	CYP1B1	Pathogenic	reviewed by expert panel
523782	NM_000104.4(CYP1B1):c.1330C>T (p.Arg444Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
523943	NM_000104.4(CYP1B1):c.535del (p.Ala179fs)	CYP1B1	Pathogenic	reviewed by expert panel
592512	NM_000104.4(CYP1B1):c.1169G>A (p.Arg390His)	CYP1B1	Pathogenic	reviewed by expert panel
7730	NM_000104.4(CYP1B1):c.182G>A (p.Gly61Glu)	CYP1B1	Pathogenic	reviewed by expert panel
7733	NM_000104.4(CYP1B1):c.1405C>T (p.Arg469Trp)	CYP1B1	Pathogenic	reviewed by expert panel
7735	NM_000104.4(CYP1B1):c.1159G>A (p.Glu387Lys)	CYP1B1	Pathogenic	reviewed by expert panel
7736	NM_000104.4(CYP1B1):c.2T>C (p.Met1Thr)	CYP1B1	Pathogenic	reviewed by expert panel
917724	NM_000104.4(CYP1B1):c.517G>A (p.Glu173Lys)	CYP1B1	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
1338800	NM_000104.4(CYP1B1):c.710C>A (p.Ala237Glu)	CYP1B1	Likely pathogenic	reviewed by expert panel
1489392	NM_000104.4(CYP1B1):c.1102C>T (p.Arg368Cys)	CYP1B1	Likely pathogenic	reviewed by expert panel
2681123	NM_000104.4(CYP1B1):c.1153C>T (p.Leu385Phe)	CYP1B1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3251434	NM_000104.4(CYP1B1):c.1412T>G (p.Ile471Ser)	CYP1B1	Likely pathogenic	criteria provided, single submitter
3339803	NM_000104.4(CYP1B1):c.781T>C (p.Phe261Leu)	CYP1B1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3896352	NM_000104.4(CYP1B1):c.3G>A (p.Met1Ile)	CYP1B1	Likely pathogenic	criteria provided, single submitter
4535961	NM_000104.4(CYP1B1):c.353C>G (p.Pro118Arg)	CYP1B1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 7 · 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
TEK	Definitive	Autosomal dominant	primary congenital glaucoma	9

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TEK	HGNC:11724	ENSG00000120156	Q02763	Angiopoietin-1 receptor	gencc
CYP1B1	HGNC:2597	ENSG00000138061	Q16678	Cytochrome P450 1B1	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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	13.9×	0.142
Other/Unknown	1	0.9×	0.805

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

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
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

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYP1B1	2,883
TEK	2,762

Intra-cohort edges

A	B	Sources
CYP1B1	TEK	intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TEK	Q02763	17
CYP1B1	Q16678	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP1B1 causes Glaucoma	1	5710.0×	0.002	CYP1B1
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	713.8×	0.006	CYP1B1
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	634.4×	0.006	CYP1B1
Tie2 Signaling	1	300.5×	0.009	TEK
Endogenous sterols	1	196.9×	0.011	CYP1B1
MAPK1/MAPK3 signaling	1	65.6×	0.028	TEK
MAPK family signaling cascades	1	51.4×	0.029	TEK
Cell surface interactions at the vascular wall	1	47.6×	0.029	TEK
RAF/MAP kinase cascade	1	30.5×	0.040	TEK
Hemostasis	1	18.0×	0.060	TEK
Signal Transduction	1	5.1×	0.187	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 2 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	8426.0×	0.003	CYP1B1
trabecular meshwork development	1	4213.0×	0.003	CYP1B1
regulation of endothelial cell apoptotic process	1	4213.0×	0.003	TEK
positive regulation of angiogenesis	2	115.4×	0.003	TEK, CYP1B1
angiogenesis	2	62.4×	0.003	TEK, CYP1B1
obsolete membrane lipid catabolic process	1	2106.5×	0.004	CYP1B1
endothelial cell-cell adhesion	1	2106.5×	0.004	CYP1B1
glomerulus vasculature development	1	2106.5×	0.004	TEK
regulation of establishment or maintenance of cell polarity	1	1685.2×	0.004	TEK
Tie signaling pathway	1	1685.2×	0.004	TEK
steroid catabolic process	1	1203.7×	0.004	CYP1B1
retinal blood vessel morphogenesis	1	1203.7×	0.004	CYP1B1
toxin metabolic process	1	1053.2×	0.005	CYP1B1
omega-hydroxylase P450 pathway	1	766.0×	0.006	CYP1B1
blood vessel endothelial cell migration	1	702.2×	0.006	CYP1B1
negative regulation of cell adhesion mediated by integrin	1	648.1×	0.006	CYP1B1
regulation of vascular permeability	1	561.7×	0.006	TEK
heart trabecula formation	1	561.7×	0.006	TEK
retinal metabolic process	1	468.1×	0.007	CYP1B1
definitive hemopoiesis	1	468.1×	0.007	TEK
epoxygenase P450 pathway	1	443.5×	0.007	CYP1B1
intrinsic apoptotic signaling pathway in response to oxidative stress	1	421.3×	0.007	CYP1B1
sterol metabolic process	1	421.3×	0.007	CYP1B1
blood vessel morphogenesis	1	401.2×	0.007	CYP1B1
regulation of reactive oxygen species metabolic process	1	366.4×	0.007	CYP1B1
nitric oxide biosynthetic process	1	351.1×	0.007	CYP1B1
positive regulation of Rac protein signal transduction	1	324.1×	0.007	TEK
positive regulation of focal adhesion assembly	1	324.1×	0.007	TEK
positive regulation of intracellular signal transduction	1	324.1×	0.007	TEK
estrogen metabolic process	1	312.1×	0.007	CYP1B1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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

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: 2; 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	0

Undrugged target profiles

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

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