glaucoma 1, open angle, O

Summary

glaucoma 1, open angle, O (MONDO:0013134) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glaucoma 1, open angle, O
Mondo ID	MONDO:0013134
MeSH	C567753
OMIM	613100
UMLS	C2751294
MedGen	416515
GARD	0024902
Is cancer (heuristic)	no

Also known as: glaucoma 1, open angle, 1O · glaucoma 1, open angle, O · glaucoma 1, open angle, type O · GLC1O · NTF4 open-angle glaucoma · open-angle glaucoma caused by mutation in NTF4

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › glaucoma › open-angle glaucoma › glaucoma 1, open angle, O

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

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

3 retrieved; paginated sample, class counts are floors:

2 likely benign, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
14019	NM_006179.5(NTF4):c.617G>A (p.Arg206Gln)	NTF4	no classifications from unflagged records	no classifications from unflagged records
14017	NM_006179.5(NTF4):c.263C>T (p.Ala88Val)	NTF4	Likely benign	criteria provided, multiple submitters, no conflicts
14018	NM_006179.5(NTF4):c.616C>T (p.Arg206Trp)	NTF4	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
NTF4	Limited	Autosomal dominant	glaucoma 1, open angle, O

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
NTF4	HGNC:8024	ENSG00000225950	P34130	Neurotrophin-4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NTF4	Neurotrophin-4	Target-derived survival factor for peripheral sensory sympathetic neurons.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NTF4	Other/Unknown	no		Nerve_growth_factor-rel, Nerve_growth_factor_CS, Nerve_growth_factor-like

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
male germ line stem cell (sensu Vertebrata) in testis	1
skeletal muscle tissue	1
skin of abdomen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NTF4	93	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, skeletal muscle tissue, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NTF4	985

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NTF4	P34130	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
NTF4 activates NTRK2 (TRKB) signaling	1	5710.0×	0.001	NTF4
Activated NTRK2 signals through PLCG1	1	2855.0×	0.001	NTF4
Activated NTRK2 signals through PI3K	1	1631.4×	0.002	NTF4
Activated NTRK2 signals through RAS	1	1142.0×	0.002	NTF4
Activated NTRK2 signals through FRS2 and FRS3	1	951.7×	0.002	NTF4
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.011	NTF4
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	NTF4
PIP3 activates AKT signaling	1	66.8×	0.015	NTF4

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
sensory organ boundary specification	1	16852.0×	4e-04	NTF4
taste bud development	1	16852.0×	4e-04	NTF4
ganglion mother cell fate determination	1	8426.0×	6e-04	NTF4
mechanoreceptor differentiation	1	3370.4×	0.001	NTF4
ameloblast differentiation	1	2106.5×	0.001	NTF4
nerve growth factor signaling pathway	1	1296.3×	0.002	NTF4
nerve development	1	936.2×	0.002	NTF4
innervation	1	887.0×	0.002	NTF4
long-term memory	1	421.3×	0.004	NTF4
adult locomotory behavior	1	300.9×	0.005	NTF4
neuron projection morphogenesis	1	276.3×	0.005	NTF4
epidermis development	1	210.7×	0.006	NTF4
modulation of chemical synaptic transmission	1	183.2×	0.006	NTF4
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.006	NTF4
negative regulation of neuron apoptotic process	1	110.9×	0.009	NTF4

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NTF4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	NTF4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NTF4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.