glaucoma 3, primary congenital, E

Summary

glaucoma 3, primary congenital, E (MONDO:0014998) is a disease caused by TEK (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TEK (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 36

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glaucoma 3, primary congenital, E
Mondo ID	MONDO:0014998
OMIM	617272
UMLS	C4310639
MedGen	934606
GARD	0018227
Is cancer (heuristic)	no

Also known as: glaucoma 3, primary congenital, E · glaucoma 3, primary congenital, E; GLC3E · glaucoma 3, primary congenital, type E · GLC3E

Data availability: 36 ClinVar variants · 2 GenCC gene-disease records.

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 congenital, E

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

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

36 retrieved; paginated sample, class counts are floors:

13 likely pathogenic, 9 uncertain significance, 7 benign, 4 conflicting classifications of pathogenicity, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
374838	NM_000459.5(TEK):c.921C>A (p.Tyr307Ter)	TEK	Pathogenic	no assertion criteria provided
374839	NM_000459.5(TEK):c.448G>T (p.Glu150Ter)	TEK	Pathogenic	no assertion criteria provided
3780702	NM_000459.5(TEK):c.1552C>T (p.Gln518Ter)	TEK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333305	NM_000459.5(TEK):c.1490-1G>A	TEK	Likely pathogenic	criteria provided, single submitter
1333408	NM_000459.5(TEK):c.470_471insTGGT (p.Lys157fs)	TEK	Likely pathogenic	criteria provided, single submitter
1333465	NM_000459.5(TEK):c.3251C>G (p.Ser1084Ter)	TEK	Likely pathogenic	criteria provided, single submitter
1333491	NM_000459.5(TEK):c.154dup (p.His52fs)	TEK	Likely pathogenic	criteria provided, single submitter
1687360	NM_000459.5(TEK):c.3165C>A (p.Tyr1055Ter)	TEK	Likely pathogenic	criteria provided, single submitter
2582395	NM_000459.5(TEK):c.434del (p.Lys145fs)	TEK	Likely pathogenic	criteria provided, single submitter
3235894	NM_000459.5(TEK):c.3200+1G>A	TEK	Likely pathogenic	criteria provided, single submitter
3236691	NM_000459.5(TEK):c.3011G>A (p.Trp1004Ter)	TEK	Likely pathogenic	criteria provided, single submitter
3236693	NM_000459.5(TEK):c.475+1G>T	TEK	Likely pathogenic	criteria provided, single submitter
3376501	NM_000459.5(TEK):c.2491G>T (p.Gly831Trp)	TEK	Likely pathogenic	criteria provided, single submitter
3780703	NM_000459.5(TEK):c.578del (p.Tyr193fs)	TEK	Likely pathogenic	criteria provided, single submitter
4813690	NM_000459.5(TEK):c.1284del (p.Val429fs)	TEK	Likely pathogenic	criteria provided, single submitter
804257	NM_000459.5(TEK):c.578A>G (p.Tyr193Cys)	TEK	Likely pathogenic	criteria provided, single submitter
366393	NM_000459.5(TEK):c.309A>C (p.Glu103Asp)	TEK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
431835	NM_000459.5(TEK):c.2078C>T (p.Thr693Ile)	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
930496	NM_000459.5(TEK):c.2773G>A (p.Ala925Thr)	TEK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333386	NM_000459.5(TEK):c.857G>T (p.Gly286Val)	TEK	Uncertain significance	criteria provided, single submitter
1333535	NM_000459.5(TEK):c.3263T>C (p.Ile1088Thr)	TEK	Uncertain significance	criteria provided, single submitter
1333692	NM_000459.5(TEK):c.32G>A (p.Gly11Glu)	TEK	Uncertain significance	criteria provided, single submitter
2570605	NM_000459.5(TEK):c.2062A>G (p.Lys688Glu)	TEK	Uncertain significance	no assertion criteria provided
3600457	NM_000459.5(TEK):c.3226C>T (p.Arg1076Trp)	TEK	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892628	NM_000459.5(TEK):c.2474A>G (p.Lys825Arg)	TEK	Uncertain significance	criteria provided, single submitter
3892631	NM_000459.5(TEK):c.546G>C (p.Gln182His)	TEK	Uncertain significance	criteria provided, single submitter
4293288	NM_000459.5(TEK):c.2854A>G (p.Met952Val)	TEK	Uncertain significance	criteria provided, single submitter
931734	NM_000459.5(TEK):c.922G>A (p.Gly308Arg)	TEK	Uncertain significance	criteria provided, single submitter
1239437	NM_000459.5(TEK):c.761-40C>T	TEK	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 4 · 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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TEK	HGNC:11724	ENSG00000120156	Q02763	Angiopoietin-1 receptor	gencc,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…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
right lung	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TEK	223	broad	marker	right lung, diaphragm, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TEK	2,762

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TEK	Q02763	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Tie2 Signaling	1	601.0×	0.012	TEK
MAPK1/MAPK3 signaling	1	131.3×	0.018	TEK
MAPK family signaling cascades	1	102.9×	0.018	TEK
Cell surface interactions at the vascular wall	1	95.2×	0.018	TEK
RAF/MAP kinase cascade	1	61.1×	0.023	TEK
Hemostasis	1	36.0×	0.032	TEK
Signal Transduction	1	10.2×	0.098	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of endothelial cell apoptotic process	1	8426.0×	0.002	TEK
glomerulus vasculature development	1	4213.0×	0.002	TEK
regulation of establishment or maintenance of cell polarity	1	3370.4×	0.002	TEK
Tie signaling pathway	1	3370.4×	0.002	TEK
regulation of vascular permeability	1	1123.5×	0.004	TEK
heart trabecula formation	1	1123.5×	0.004	TEK
definitive hemopoiesis	1	936.2×	0.004	TEK
positive regulation of Rac protein signal transduction	1	648.1×	0.004	TEK
positive regulation of focal adhesion assembly	1	648.1×	0.004	TEK
positive regulation of intracellular signal transduction	1	648.1×	0.004	TEK
positive regulation of Rho protein signal transduction	1	581.1×	0.004	TEK
endothelial cell proliferation	1	543.6×	0.004	TEK
negative regulation of endothelial cell apoptotic process	1	495.6×	0.004	TEK
sprouting angiogenesis	1	481.5×	0.004	TEK
substrate adhesion-dependent cell spreading	1	343.9×	0.006	TEK
positive regulation of endothelial cell migration	1	251.5×	0.007	TEK
positive regulation of endothelial cell proliferation	1	230.8×	0.008	TEK
cellular response to mechanical stimulus	1	216.1×	0.008	TEK
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.009	TEK
negative regulation of angiogenesis	1	168.5×	0.009	TEK
negative regulation of inflammatory response	1	137.0×	0.010	TEK
positive regulation of angiogenesis	1	115.4×	0.012	TEK
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.015	TEK
positive regulation of MAPK cascade	1	80.6×	0.015	TEK
heart development	1	78.8×	0.015	TEK
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.015	TEK
cell-cell signaling	1	69.6×	0.016	TEK
cell surface receptor signaling pathway	1	64.1×	0.017	TEK
angiogenesis	1	62.4×	0.017	TEK
negative regulation of apoptotic process	1	34.8×	0.029	TEK

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TEK	46	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	TEK
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
LINIFANIB	3	TEK
BRIVANIB	3	TEK
CEDIRANIB	3	TEK
LESTAURTINIB	3	TEK
DORAMAPIMOD	2	TEK
FORETINIB	2	TEK
REBASTINIB	2	TEK
CEP-11981	2	TEK
DEFOSBARASERTIB	2	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

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	TEK
NINTEDANIB	4	TEK
QUIZARTINIB	4	TEK
CRIZOTINIB	4	TEK
MIDOSTAURIN	4	TEK
LOPERAMIDE	4	TEK
LINIFANIB	3	TEK
BRIVANIB	3	TEK
CEDIRANIB	3	TEK
LESTAURTINIB	3	TEK
DORAMAPIMOD	2	TEK
FORETINIB	2	TEK
REBASTINIB	2	TEK
CEP-11981	2	TEK
DEFOSBARASERTIB	2	TEK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	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	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: 0.