glaucoma 1, open angle, P

Summary

glaucoma 1, open angle, P (MONDO:0008328) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glaucoma 1, open angle, P
Mondo ID	MONDO:0008328
MeSH	C566748
OMIM	177700
UMLS	C3888338
MedGen	854866
GARD	0024617
Is cancer (heuristic)	no

Also known as: glaucoma 1, open angle, P · glaucoma 1, open angle, type P · GLC1P

Data availability: 6 ClinVar variants.

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, P

Related subtypes (6): residual stage of open angle glaucoma, low tension glaucoma, glaucoma type 1C, glaucoma 1, open angle, O, 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

6 retrieved; paginated sample, class counts are floors:

3 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
403521	NM_013254.4(TBK1):c.229-4dup	TBK1	Benign	criteria provided, multiple submitters, no conflicts
403522	NM_013254.4(TBK1):c.978T>A (p.Ile326=)	TBK1	Benign	criteria provided, multiple submitters, no conflicts
475935	NM_013254.4(TBK1):c.1391T>C (p.Val464Ala)	TBK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
475937	NM_013254.4(TBK1):c.1960-10G>T	TBK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
475941	NM_013254.4(TBK1):c.66T>C (p.Asn22=)	TBK1	Benign	criteria provided, multiple submitters, no conflicts
522363	NM_013254.4(TBK1):c.541-9del	TBK1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBK1	Orphanet:1930	Herpes simplex virus encephalitis
TBK1	Orphanet:275872	Frontotemporal dementia with motor neuron disease
TBK1	Orphanet:803	Amyotrophic lateral sclerosis

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
TBK1	HGNC:11584	ENSG00000183735	Q9UHD2	Serine/threonine-protein kinase TBK1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBK1	Serine/threonine-protein kinase TBK1	Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents.

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)
TBK1	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS

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
calcaneal tendon	1
colonic epithelium	1
lateral nuclear group of thalamus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBK1	284	ubiquitous	marker	colonic epithelium, calcaneal tendon, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBK1	5,476

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBK1	Q9UHD2	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 47. 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
STAT6-mediated induction of chemokines	1	3806.7×	0.006	TBK1
IRF3 mediated activation of type 1 IFN	1	1903.3×	0.006	TBK1
ZBP1(DAI) mediated induction of type I IFNs	1	1038.2×	0.006	TBK1
STING mediated induction of host immune responses	1	1038.2×	0.006	TBK1
Mitophagy	1	1038.2×	0.006	TBK1
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation	1	951.7×	0.006	TBK1
IRF3-mediated induction of type I IFN	1	815.7×	0.006	TBK1
TICAM1-dependent activation of IRF3/IRF7	1	815.7×	0.006	TBK1
Regulation of innate immune responses to cytosolic DNA	1	761.3×	0.006	TBK1
TRAF3-dependent IRF activation pathway	1	761.3×	0.006	TBK1
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	1	761.3×	0.006	TBK1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	601.0×	0.007	TBK1
Interleukin-37 signaling	1	519.1×	0.007	TBK1
TNFR1-induced proapoptotic signaling	1	439.2×	0.007	TBK1
TNF signaling	1	423.0×	0.007	TBK1
TRAF6 mediated IRF7 activation	1	380.7×	0.008	TBK1
PINK1-PRKN Mediated Mitophagy	1	356.9×	0.008	TBK1
Negative regulators of DDX58/IFIH1 signaling	1	326.3×	0.008	TBK1
Cytosolic sensors of pathogen-associated DNA	1	285.5×	0.008	TBK1
Selective autophagy	1	278.5×	0.008	TBK1
Interleukin-1 family signaling	1	271.9×	0.008	TBK1
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.008	TBK1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	253.8×	0.008	TBK1
Regulation of TNFR1 signaling	1	223.9×	0.009	TBK1
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.009	TBK1
TRIF (TICAM1)-mediated TLR4 signaling	1	190.3×	0.009	TBK1
MyD88-independent TLR4 cascade	1	184.2×	0.009	TBK1
SARS-CoV-1-host interactions	1	175.7×	0.010	TBK1
Autophagy	1	148.3×	0.011	TBK1
SARS-CoV-1 Infection	1	142.8×	0.011	TBK1

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
dendritic cell proliferation	1	5617.3×	0.004	TBK1
cGAS/STING signaling pathway	1	3370.4×	0.004	TBK1
positive regulation of xenophagy	1	2106.5×	0.004	TBK1
positive regulation of TORC2 signaling	1	2106.5×	0.004	TBK1
regulation of type I interferon production	1	1685.2×	0.004	TBK1
T follicular helper cell differentiation	1	1404.3×	0.004	TBK1
cytoplasmic pattern recognition receptor signaling pathway	1	887.0×	0.004	TBK1
peptidyl-threonine phosphorylation	1	887.0×	0.004	TBK1
positive regulation of type I interferon-mediated signaling pathway	1	842.6×	0.004	TBK1
positive regulation of interferon-alpha production	1	648.1×	0.005	TBK1
positive regulation of macroautophagy	1	526.6×	0.005	TBK1
toll-like receptor 4 signaling pathway	1	526.6×	0.005	TBK1
peptidyl-serine phosphorylation	1	495.6×	0.005	TBK1
activation of innate immune response	1	481.5×	0.005	TBK1
positive regulation of type I interferon production	1	421.3×	0.005	TBK1
positive regulation of interferon-beta production	1	391.9×	0.005	TBK1
canonical NF-kappaB signal transduction	1	366.4×	0.005	TBK1
type I interferon-mediated signaling pathway	1	343.9×	0.005	TBK1
negative regulation of TORC1 signaling	1	324.1×	0.005	TBK1
positive regulation of TORC1 signaling	1	295.6×	0.005	TBK1
macroautophagy	1	240.7×	0.006	TBK1
antiviral innate immune response	1	227.7×	0.006	TBK1
positive regulation of autophagy	1	208.1×	0.007	TBK1
response to virus	1	144.0×	0.009	TBK1
defense response to Gram-positive bacterium	1	127.7×	0.010	TBK1
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.016	TBK1
defense response to virus	1	69.3×	0.016	TBK1
negative regulation of gene expression	1	69.1×	0.016	TBK1
protein phosphorylation	1	68.0×	0.016	TBK1
inflammatory response	1	37.7×	0.028	TBK1

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
TBK1	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TBK1	38	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	TBK1
AMLEXANOX	4	TBK1
FEDRATINIB	4	TBK1
RUXOLITINIB	4	TBK1
ENTRECTINIB	4	TBK1
PACRITINIB	4	TBK1
BOSUTINIB	4	TBK1
FILGOTINIB	4	TBK1
NINTEDANIB	4	TBK1
SUNITINIB	4	TBK1
ERLOTINIB	4	TBK1
CRIZOTINIB	4	TBK1
MIDOSTAURIN	4	TBK1
ORANTINIB	3	TBK1
ALVOCIDIB	3	TBK1
DOVITINIB	3	TBK1
LESTAURTINIB	3	TBK1
RUBOXISTAURIN	3	TBK1
SILMITASERTIB	2	TBK1
FORETINIB	2	TBK1
SU-014813	2	TBK1
CENISERTIB	2	TBK1
ADAVOSERTIB	2	TBK1
CERDULATINIB	2	TBK1
R-406	2	TBK1
AT-9283	2	TBK1
MILCICLIB	2	TBK1
TOZASERTIB	2	TBK1
UCN-01	2	TBK1
PF-00562271	1	TBK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TBK1	475	Binding:473, Functional:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TBK1	475

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)
MOMELOTINIB	4	TBK1
AMLEXANOX	4	TBK1
FEDRATINIB	4	TBK1
RUXOLITINIB	4	TBK1
ENTRECTINIB	4	TBK1
PACRITINIB	4	TBK1
BOSUTINIB	4	TBK1
FILGOTINIB	4	TBK1
NINTEDANIB	4	TBK1
SUNITINIB	4	TBK1
ERLOTINIB	4	TBK1
CRIZOTINIB	4	TBK1
MIDOSTAURIN	4	TBK1
ORANTINIB	3	TBK1
ALVOCIDIB	3	TBK1
DOVITINIB	3	TBK1
LESTAURTINIB	3	TBK1
RUBOXISTAURIN	3	TBK1
SILMITASERTIB	2	TBK1
FORETINIB	2	TBK1
SU-014813	2	TBK1
CENISERTIB	2	TBK1
ADAVOSERTIB	2	TBK1
CERDULATINIB	2	TBK1
R-406	2	TBK1
AT-9283	2	TBK1
MILCICLIB	2	TBK1
TOZASERTIB	2	TBK1
UCN-01	2	TBK1
PF-00562271	1	TBK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TBK1
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.