Congenital glaucoma

Summary

Congenital glaucoma (MONDO:0020366) is a disease caused by THBS1 (GenCC Strong), with 9 cohort genes and 23 clinical trials.

At a glance

• Causal gene: THBS1 (GenCC Strong)
• Cohort genes: 9
• ClinVar variants: 319
• Clinical trials: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital glaucoma
Mondo ID	MONDO:0020366
MeSH	D006871
DOID	DOID:11212
NCIT	C50648
SNOMED CT	204113001
UMLS	C0020302
MedGen	42532
GARD	0025157
Is cancer (heuristic)	no

Also known as: buphthalmia · buphthalmos · Buphthalmus · hydrophthalmos · primary congenital glaucoma

Data availability: 319 ClinVar variants · 7 GenCC gene-disease records · 2 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (11): glaucoma with elevated episcleral venous pressure, exfoliation syndrome, glaucoma 1, open angle, P, iris hypoplasia with glaucoma, glaucoma 1, open angle, O, glaucoma secondary to spherophakia/ectopia lentis and megalocornea, juvenile open angle glaucoma, anterior segment dysgenesis 3, hereditary glaucoma, primary closed-angle, OPTN-related open angle glaucoma, TEK-related primary glaucoma

Subtypes (4): primary congenital glaucoma, glaucoma 3, primary infantile, B, 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

319 retrieved; paginated sample, class counts are floors:

199 likely benign, 43 pathogenic, 23 conflicting classifications of pathogenicity, 22 uncertain significance, 12 pathogenic/likely pathogenic, 11 benign, 7 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2422363	NC_000002.11:g.(?38297865)(38917056_?)del	ATL2	Pathogenic	criteria provided, single submitter
1076484	NM_000104.4(CYP1B1):c.840C>A (p.Cys280Ter)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1203967	NM_000104.4(CYP1B1):c.1A>G (p.Met1Val)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1254629	NM_000104.4(CYP1B1):c.1310C>T (p.Pro437Leu)	CYP1B1	Pathogenic	reviewed by expert panel
1324202	NM_000104.4(CYP1B1):c.1390dup (p.Ser464fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1335387	NM_000104.4(CYP1B1):c.797GCAACTTCA[1] (p.Ser269_Phe271del)	CYP1B1	Pathogenic	reviewed by expert panel
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
1442930	NM_000104.4(CYP1B1):c.55C>T (p.Gln19Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2098650	NM_000104.4(CYP1B1):c.350G>T (p.Arg117Leu)	CYP1B1	Pathogenic	criteria provided, single submitter
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
2203050	NM_000104.4(CYP1B1):c.217_218del (p.Ser73fs)	CYP1B1	Pathogenic	criteria provided, single submitter
2577219	NM_000104.4(CYP1B1):c.317C>A (p.Ala106Asp)	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
2681129	NM_000104.4(CYP1B1):c.346_363del (p.Asp116_Ala121del)	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
2681133	NM_000104.4(CYP1B1):c.575A>T (p.Asp192Val)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681137	NM_000104.4(CYP1B1):c.868del (p.Arg290fs)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2681138	NM_000104.4(CYP1B1):c.1140dup (p.Val381fs)	CYP1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2681139	NM_000104.4(CYP1B1):c.1023G>A (p.Trp341Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2705933	NM_000104.4(CYP1B1):c.2T>G (p.Met1Arg)	CYP1B1	Pathogenic	criteria provided, single submitter
2710978	NM_000104.4(CYP1B1):c.873_877dup (p.Met293delinsThrTer)	CYP1B1	Pathogenic	criteria provided, single submitter
2720250	NM_000104.4(CYP1B1):c.1425_1428del (p.Ser476fs)	CYP1B1	Pathogenic	criteria provided, single submitter
2734165	NM_000104.4(CYP1B1):c.243C>G (p.Tyr81Ter)	CYP1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
2764029	NM_000104.4(CYP1B1):c.836_863del (p.His279fs)	CYP1B1	Pathogenic	criteria provided, single submitter
2768652	NM_000104.4(CYP1B1):c.243del (p.Arg80_Tyr81insTer)	CYP1B1	Pathogenic	criteria provided, single submitter
282564	NM_000104.4(CYP1B1):c.1064_1076del (p.Arg355fs)	CYP1B1	Pathogenic	reviewed by expert panel
2827579	NM_000104.4(CYP1B1):c.982_990del (p.Phe328_Ala330del)	CYP1B1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 69 · Orphanet: 16 · 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
CYP1B1	Definitive	Autosomal recessive	CYP1B1-related glaucoma with or without anterior segment dysgenesis	6
LTBP2	Definitive	Autosomal recessive	microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma	20
LTBP3	Definitive	Autosomal recessive	microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma	20
MYOC	Definitive	Autosomal dominant	glaucoma 1, open angle, A	7
TEK	Definitive	Autosomal dominant	primary congenital glaucoma	9
THBS1	Strong	Autosomal dominant	congenital glaucoma	2
GPATCH3	Limited	Autosomal recessive	congenital glaucoma
TCF7L2	Limited	Unknown	congenital glaucoma	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYP1B1	Orphanet:708	Peters anomaly
CYP1B1	Orphanet:98976	Congenital glaucoma
CYP1B1	Orphanet:98977	Juvenile glaucoma
TCF7L2	Orphanet:528084	Non-specific syndromic intellectual disability
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
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
MYOC	Orphanet:98976	Congenital glaucoma
MYOC	Orphanet:98977	Juvenile glaucoma

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CYP1B1	HGNC:2597	ENSG00000138061	Q16678	Cytochrome P450 1B1	gencc,clinvar
TCF7L2	HGNC:11641	ENSG00000148737	Q9NQB0	Transcription factor 7-like 2	gencc
TEK	HGNC:11724	ENSG00000120156	Q02763	Angiopoietin-1 receptor	gencc
THBS1	HGNC:11785	ENSG00000137801	P07996	Thrombospondin-1	gencc
GPATCH3	HGNC:25720	ENSG00000198746	Q96I76	G patch domain-containing protein 3	gencc
LTBP2	HGNC:6715	ENSG00000119681	Q14767	Latent-transforming growth factor beta-binding protein 2	gencc
LTBP3	HGNC:6716	ENSG00000168056	Q9NS15	Latent-transforming growth factor beta-binding protein 3	gencc
MYOC	HGNC:7610	ENSG00000034971	Q99972	Myocilin	gencc
ATL2	HGNC:24047	ENSG00000119787	Q8NHH9	Atlastin-2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYP1B1	Cytochrome P450 1B1	A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins.
TCF7L2	Transcription factor 7-like 2	Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner.
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…
THBS1	Thrombospondin-1	Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions.
GPATCH3	G patch domain-containing protein 3	Involved in transcriptional regulation.
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.
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.
ATL2	Atlastin-2	Atlastin-2 (ATL2) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 8 · Druggable fraction: 0.11

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	8	1.6×	0.085
Kinase	1	3.1×	0.282

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CYP1B1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
TCF7L2	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
TEK	Kinase	yes	2.7.10.1	Prot_kinase_dom, EGF, Ser-Thr/Tyr_kinase_cat_dom
THBS1	Other/Unknown	no		EGF, TSP1_rpt, VWF_dom
GPATCH3	Other/Unknown	no		G_patch_dom, GPATCH3
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
MYOC	Other/Unknown	no		Olfac-like_dom, Olfactomedin-like_domain
ATL2	Other/Unknown	no		Guanylate-bd/ATL_C, Guanylate-bd_N, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

8 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pericardium	2
mucosa of stomach	2
ascending aorta	2
descending thoracic aorta	2
thoracic aorta	2
cartilage tissue	1
synovial joint	1
endothelial cell	1
lateral nuclear group of thalamus	1
pancreatic ductal cell	1
diaphragm	1
right lung	1
visceral pleura	1
stromal cell of endometrium	1
granulocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
calcaneal tendon	1
esophagogastric junction muscularis propria	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYP1B1	285	ubiquitous	marker	pericardium, cartilage tissue, synovial joint
TCF7L2	291	ubiquitous	marker	lateral nuclear group of thalamus, endothelial cell, pancreatic ductal cell
TEK	223	broad	marker	right lung, diaphragm, visceral pleura
THBS1	271	ubiquitous	marker	stromal cell of endometrium, mucosa of stomach, pericardium
GPATCH3	180	ubiquitous	yes	primordial germ cell in gonad, granulocyte, male germ line stem cell (sensu Vertebrata) in testis
LTBP2	276	ubiquitous	marker	descending thoracic aorta, thoracic aorta, ascending aorta
LTBP3	279	broad	marker	descending thoracic aorta, thoracic aorta, ascending aorta
MYOC	201	tissue_specific	marker	calcaneal tendon, mucosa of stomach, esophagogastric junction muscularis propria
ATL2	268	ubiquitous	marker	secondary oocyte, oocyte, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
THBS1	5,731
TCF7L2	3,775
CYP1B1	2,883
TEK	2,762
LTBP2	2,658
LTBP3	2,339
MYOC	1,272
ATL2	1,227
GPATCH3	588

Intra-cohort edges

A	B	Sources
CYP1B1	LTBP2	string_interaction
CYP1B1	MYOC	string_interaction
CYP1B1	TEK	intact
LTBP2	MYOC	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYOC	Q99972	24
TEK	Q02763	17
THBS1	P07996	11
TCF7L2	Q9NQB0	3
CYP1B1	Q16678	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATL2	Q8NHH9	84.36
GPATCH3	Q96I76	68.01
LTBP3	Q9NS15	64.21
LTBP2	Q14767	58.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 55. Enrichment computed across 9 evidence-associated genes (7 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 7 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	96.0×	0.004	LTBP2, LTBP3
TGF-beta receptor signaling activates SMADs	2	93.2×	0.004	LTBP2, LTBP3
Molecules associated with elastic fibres	2	88.2×	0.004	LTBP2, LTBP3
Defective CYP1B1 causes Glaucoma	1	1631.4×	0.007	CYP1B1
Signaling by TGF-beta Receptor Complex	2	57.2×	0.007	LTBP2, LTBP3
Signaling by TGFB family members	2	33.0×	0.014	LTBP2, LTBP3
Signaling by TCF7L2 mutants	1	407.9×	0.018	TCF7L2
Signal Transduction	4	5.8×	0.018	TCF7L2, TEK, LTBP2, LTBP3
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	203.9×	0.026	CYP1B1
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)	1	181.3×	0.026	CYP1B1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	163.1×	0.026	TCF7L2
RUNX3 regulates WNT signaling	1	163.1×	0.026	TCF7L2
Extracellular matrix organization	2	18.0×	0.026	LTBP2, LTBP3
Incretin synthesis, secretion, and inactivation	1	148.3×	0.026	TCF7L2
Repression of WNT target genes	1	102.0×	0.034	TCF7L2
Formation of definitive endoderm	1	102.0×	0.034	TCF7L2
Tie2 Signaling	1	85.9×	0.035	TEK
Signaling by WNT in cancer	1	85.9×	0.035	TCF7L2
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	81.6×	0.035	TCF7L2
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	74.2×	0.037	TCF7L2
Syndecan interactions	1	60.4×	0.043	THBS1
Endogenous sterols	1	56.3×	0.044	CYP1B1
Dengue Virus Genome Translation and Replication	1	45.3×	0.048	ATL2
Defective B3GALTL causes PpS	1	44.1×	0.048	THBS1
O-glycosylation of TSR domain-containing proteins	1	42.9×	0.048	THBS1
Beta-catenin independent WNT signaling	1	41.8×	0.048	TCF7L2
Peptide hormone metabolism	1	38.8×	0.048	TCF7L2
Transcriptional regulation by RUNX3	1	38.8×	0.048	TCF7L2
Transcriptional Regulation by VENTX	1	37.9×	0.048	TCF7L2
Gastrulation	1	37.1×	0.048	TCF7L2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	4	34.8×	6e-04	TCF7L2, TEK, THBS1, MYOC
negative regulation of cell-matrix adhesion	2	197.1×	0.003	THBS1, MYOC
positive regulation of angiogenesis	3	38.5×	0.003	CYP1B1, TEK, THBS1
positive regulation of focal adhesion assembly	2	144.0×	0.004	TEK, MYOC
sprouting angiogenesis	2	107.0×	0.005	TEK, THBS1
negative regulation of extrinsic apoptotic signaling pathway	2	93.6×	0.006	TCF7L2, THBS1
negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	1872.4×	0.008	THBS1
skeletal muscle hypertrophy	1	1872.4×	0.008	MYOC
benzene-containing compound metabolic process	1	1872.4×	0.008	CYP1B1
negative regulation of nitric oxide-cGMP mediated signal transduction	1	1872.4×	0.008	THBS1
response to glucose	2	56.7×	0.008	TCF7L2, THBS1
positive regulation of endothelial cell migration	2	55.9×	0.008	TEK, THBS1
trabecular meshwork development	1	936.2×	0.013	CYP1B1
obsolete negative regulation of nitric oxide mediated signal transduction	1	936.2×	0.013	THBS1
regulation of endothelial cell apoptotic process	1	936.2×	0.013	TEK
negative regulation of angiogenesis	2	37.5×	0.014	TEK, THBS1
transforming growth factor beta receptor signaling pathway	2	35.3×	0.015	LTBP2, LTBP3
negative regulation of endothelial cell chemotaxis	1	624.1×	0.016	THBS1
negative regulation of dendritic cell antigen processing and presentation	1	468.1×	0.016	THBS1
negative regulation of long-chain fatty acid import across plasma membrane	1	468.1×	0.016	THBS1
positive regulation of heparan sulfate proteoglycan biosynthetic process	1	468.1×	0.016	TCF7L2
obsolete membrane lipid catabolic process	1	468.1×	0.016	CYP1B1
endothelial cell-cell adhesion	1	468.1×	0.016	CYP1B1
glomerulus vasculature development	1	468.1×	0.016	TEK
endoplasmic reticulum membrane fusion	1	374.5×	0.016	ATL2
regulation of hormone metabolic process	1	374.5×	0.016	TCF7L2
regulation of establishment or maintenance of cell polarity	1	374.5×	0.016	TEK
maintenance of DNA repeat elements	1	374.5×	0.016	TCF7L2
Tie signaling pathway	1	374.5×	0.016	TEK
myoblast fate commitment	1	374.5×	0.016	TCF7L2

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 7

Druggability breadth: 5 of 9 evidence-associated genes (56%) 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
TEK	CETIRIZINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TEK	46	4
CYP1B1	22	4
TCF7L2	0	0
THBS1	0	0
GPATCH3	0	0
LTBP2	0	0
LTBP3	0	0
MYOC	0	0
ATL2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PAZOPANIB	4	CYP1B1, TEK
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
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
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
RESVERATROL	3	CYP1B1
BERGAPTEN	3	CYP1B1

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
TCF7L2	22	Binding:22
THBS1	8	Binding:8
MYOC	4	Binding:4

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
CYP1B1	408
TEK	707

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; 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)
PAZOPANIB	4	CYP1B1, TEK
INDACATEROL	4	CYP1B1
ESTRADIOL	4	CYP1B1
CANNABIDIOL	4	CYP1B1
BERBERINE	4	CYP1B1
MELATONIN	4	CYP1B1
ERYTHROMYCIN	4	CYP1B1
CARVEDILOL	4	CYP1B1
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
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
RESVERATROL	3	CYP1B1
BERGAPTEN	3	CYP1B1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CYP1B1, TEK
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	7	TCF7L2, THBS1, GPATCH3, LTBP2, LTBP3, MYOC, ATL2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYOC	4	CYP1B1
TCF7L2	22	—
THBS1	8	—
GPATCH3	0	—
LTBP2	0	—
LTBP3	0	—
ATL2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 23.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	20
PHASE1	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04947124	PHASE2	COMPLETED	A Study to Determine the Safety and Tolerability of 2 Concentrations of QLS-101
NCT01460017	PHASE1	UNKNOWN	Comparison Between Deep Sclerectomy and Traditional Trabeculotomy & Trabeculectomy in Congenital Glaucoma
NCT02121171	PHASE1	UNKNOWN	Combined Trab+Trab Versus Combined Trab+Trab With Subconjunctival Implantation of Ologen for Primary Congenital Glaucoma
NCT04381611	Not specified	ENROLLING_BY_INVITATION	INTEGRAL Study: A Longitudinal Study of Surgeries and Lasers in Glaucoma: Long-term Results and Success Predictors Analysed From a Large-scale Retrospective and Prospective Glaucoma Register
NCT07504315	Not specified	NOT_YET_RECRUITING	Study Aim to Compare the Effect of Different Technique of Airway Managment During Anaesthesia on the Haemodynamics and Intraocular Pressure. Patients Were Divided Into Three Groups of 25 Patients Each. (Group A); Patients Who Were Subjected to LMA Insertion (Group B ).
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
NCT01136460	Not specified	UNKNOWN	Genetic Testing in Primary Congenital Glaucoma Patients
NCT02945176	Not specified	COMPLETED	Safety and Performance Study of the ARGOS-IO System in Patients Undergoing Boston Keratoprosthesis Implantation
NCT03077789	Not specified	COMPLETED	Prospective Study of the Diagnostic and Therapeutic Management of Congenital Glaucoma in France
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
NCT05011747	Not specified	UNKNOWN	Viscotrabeculotomy in Pediatric Glaucoma Following Cataract Surgery
NCT05115708	Not specified	UNKNOWN	Kahook Dual Blade Ab-interno Trabeculotomy Versus ab Externo Viscotrabeculotomy in Primary Congenital Glaucoma
NCT05205122	Not specified	UNKNOWN	Evaluation of Primary Congenital Glaucoma at Asyut University Hospital
NCT05943184	Not specified	COMPLETED	Cognitive Behavioral Nursing Model
NCT06189326	Not specified	UNKNOWN	Non-penetrating Deep Sclerectomy Versus Trabeculotomy- Trabeculectomy Operation in Treatment of Primary Congenital Glaucoma
NCT07012252	Not specified	COMPLETED	Optical Coherence Tomography of the Irido-Corneal Angle Before and After Goniotomy and Trabeculotomy in Primary Congenital Glaucoma