gene

TBK1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TBK1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

1277Connections

5Hypotheses

3Analyses

50Outgoing

50Incoming

4Experiments

3Debates

Summary

TBK1 is a gene implicated in neurodegeneration research. Key relationships include: activates, associated with, regulates. Associated with ALS, Aging, Als. Connected to 636 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	TBK1
Full Name	Mediated Neuroinflammation Hypothesis: Autophagy Failure Drives FTD/ALS Pathogenesis
Chromosome	12q14.2
Protein Type	Serine/Threonine Kinase
Function	TBK1 belongs to the IκB kinase (IKK) subfamily of kinases, originally characterized for its role in activating innate immune signaling through the induction of type I interferons in response to viral
Primary Expression	Motor cortex, Spinal cord, Immune cells
Molecular Weight	84 kDa
Pathways	Apoptosis, Autophagy, Epigenetic, Er Stress, Immune Response
UniProt ID	Q9UHD2
NCBI Gene ID	29110
Ensembl ID	ENSG00000183735
OMIM	604834
GeneCards	TBK1
Human Protein Atlas	TBK1
Associated Diseases	Aging, Als, Alzheimer, Alzheimer's disease, amyotrophic lateral sclerosis
Known Drugs/Compounds	amlexanox, rapamycin
Interactions	Actin, AGING, AIM2, AKT, AKT1, ALS
SciDEX Hypotheses	TBK1 Loss-of-Function Amplifies C1q-Mediated Synap TBK1 Phosphorylation State Creates Phospho-Regulat
KG Connections	1277 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: TBK1 — AlphaFold Q9UHD2 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (7)

Knowledge base pages for this entity

Canonical Page

TBK1-Mediated Neuroinflammation Hypothesis — Autophagy Failure and Innate Immune Dysregulation in FTD/ALS

hypothesis · 2087 words

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TBK1 Protein

protein · 1510 words

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TBK1 Protein (TANK-Binding Kinase 1)

protein · 1482 words

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TBK1-Mediated Neuroinflammation Hypothesis — Impaired Autophagy and Innate Immune Dysregulation in FTD/ALS

mechanism · 1359 words

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TBK1 Gene

gene · 1021 words

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TBK1 Autophagy and Neuroinflammation ALS/FTD Causal Chain

mechanism · 883 words

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Pathway Diagram

graph TD
    TBK1["TBK1"] -->|"Phosphorylates"| SQSTM1["SQSTM1"]
    TBK1["TBK1"] -->|"Activates"| autophagy["autophagy"]
    TBK1["TBK1"] -->|"Phosphorylates"| p62["p62"]
    TBK1["TBK1"] -->|"Increases Risk"| p62_aggregates["p62 aggregates"]
    TBK1["TBK1"] -->|"Activates"| ULK1["ULK1"]
    TBK1["TBK1"] -->|"Phosphorylates"| P62_SQSTM1["P62_SQSTM1"]
    TBK1["TBK1"] -->|"Promotes"| mitophagy["mitophagy"]
    TBK1["TBK1"] -->|"Regulates"| OPTN["OPTN"]
    FIP200["FIP200"] -->|"Inhibits"| TBK1["TBK1"]
    amlexanox["amlexanox"] -->|"Inhibits"| TBK1["TBK1"]
    proteotoxic_stress["proteotoxic stress"] -->|"Activates"| TBK1["TBK1"]
    CGAS_STING["CGAS_STING"] -->|"Activates"| TBK1["TBK1"]
    STING1["STING1"] -->|"Activates"| TBK1["TBK1"]
    style TBK1 fill:#8d4900,color:#e0e0e0
    style SQSTM1 fill:#0d47a1,color:#e0e0e0
    style autophagy fill:#9C27B0,color:#e0e0e0
    style p62 fill:#0d47a1,color:#e0e0e0
    style p62_aggregates fill:#607D8B,color:#e0e0e0
    style ULK1 fill:#0d47a1,color:#e0e0e0
    style P62_SQSTM1 fill:#0d47a1,color:#e0e0e0
    style mitophagy fill:#1b5e20,color:#e0e0e0
    style OPTN fill:#0d47a1,color:#e0e0e0
    style FIP200 fill:#0d47a1,color:#e0e0e0
    style amlexanox fill:#00838f,color:#e0e0e0
    style proteotoxic_stress fill:#607D8B,color:#e0e0e0
    style CGAS_STING fill:#9C27B0,color:#e0e0e0
    style STING1 fill:#0d47a1,color:#e0e0e0

Outgoing (663)

Target	Relation	Type	Str
STING	activates	gene	1.00
Als	associated_with	disease	1.00
Als	activates	disease	1.00
IRF3	activates	gene	1.00
DNA	activates	gene	1.00
Immune Response	activates	pathway	1.00
CGAS-STING	activates	gene	1.00
CGAS	activates	gene	1.00
Innate Immunity	activates	pathway	1.00
Als	interacts_with	disease	0.95
frontotemporal dementia	associated_with	disease	0.95
Frontotemporal Dementia	associated_with	disease	0.95
Infection	activates	disease	0.95
Amyotrophic Lateral Sclerosis	associated_with	disease	0.95
amyotrophic lateral sclerosis	risk_factor_for	disease	0.95
autophagy	activates	pathway	0.90
p62	phosphorylates	protein	0.90
SQSTM1	phosphorylates	protein	0.90
Autophagolysosomal Dysfunction	contributes_to	phenotype	0.90
Optineurin	binds	protein	0.90
CLASS III PHOSPHATIDYLINOSITOL 3-KINASE COMPLEX I	binds	protein	0.90
OPTN	associated_with	protein	0.90
macroautophagy	regulates	process	0.90
neuroinflammation	does_not_cause	process	0.90
Autophagolysosomal dysfunction	causes	process	0.90
Motoneuron pathology	causes	pathology	0.90
amyotrophic lateral sclerosis	implicated_in	disease	0.90
Autophagy	interacts_with	pathway	0.90
Autophagy	regulates	pathway	0.90
Autophagy	activates	pathway	0.90
tau phosphorylation	upstream_of	process	0.88
Dementia	associated_with	disease	0.85
Als	inhibits	disease	0.85
Tau Phosphorylation	mediates	process	0.85
Als	regulates	disease	0.85
Inflammation	inhibits	disease	0.85
NDP52	associated_with	protein	0.85
ULK1	phosphorylates	protein	0.85
neurite outgrowth	promotes	phenotype	0.85
STING	associated_with	protein	0.85
Selective Autophagy	regulates	process	0.85
Optineurin	phosphorylates	protein	0.85
OPTN	phosphorylates	protein	0.85
Autophagolysosomal Dysfunction	regulates	phenotype	0.85
lysosomal dysfunction	prevents	phenotype	0.85
Tumor	activates	disease	0.85
ULK1	activates	protein	0.82
Primary Lateral Sclerosis	associated_with	disease	0.82
p62 aggregates	contributes_to	phenotype	0.80
unfolded protein response	participates_in	pathway	0.80

Incoming (614)

Source	Relation	Type	Str
genes-tbk1	linked_to	wiki_page	1.00
AUTOPHAGY	interacts_with	gene	1.00
STING	activates	gene	1.00
UBIQUITIN	activates	gene	1.00
ZBP1	interacts_with	protein	0.90
FIP200	inhibits	protein	0.90
amlexanox	inhibits	drug	0.90
CGAS	activates	gene	0.90
P62	activates	gene	0.90
P62	regulates	gene	0.90
NAP1	binds_to	protein	0.85
SNCA	activates	protein	0.85
STING	associated_with	protein	0.85
MARCH1	ubiquitinates	gene	0.80
BTK	activates	gene	0.80
proteotoxic stress	activates	phenotype	0.80
CYTOKINES	activates	gene	0.80
LC3	activates	gene	0.80
SQSTM1	activates	gene	0.80
STING	regulates	gene	0.80
OPTN	interacts_with	gene	0.80
AUTOPHAGY	regulates	gene	0.80
IRF3	activates	gene	0.80
ALS	associated_with	gene	0.80
GENES	activates	gene	0.80
AUTOPHAGY	activates	gene	0.80
AUTOPHAGY	inhibits	gene	0.80
FIP200	interacts_with	gene	0.80
UBIQUITIN	interacts_with	gene	0.80
CGAS_STING	activates	pathway	0.72
INFLAMMATION	inhibits	gene	0.70
NDP52	regulates	gene	0.70
MITOCHONDRIA	activates	gene	0.70
CGAS	regulates	gene	0.70
TLR3	activates	gene	0.70
IRF3	inhibits	gene	0.70
TLR4	activates	gene	0.70
TAX1BP1	regulates	gene	0.70
NBR1	regulates	gene	0.70
OPTN	activates	gene	0.70
TAX1BP1	interacts_with	gene	0.70
PARKIN	interacts_with	gene	0.70
PARKIN	associated_with	gene	0.70
STING1	activates	protein	0.70
P62	interacts_with	gene	0.70
MITOCHONDRIA	interacts_with	gene	0.70
TLR	activates	gene	0.70
OPTN	associated_with	gene	0.70
LC3	regulates	gene	0.70
INFLAMMATION	activates	gene	0.70

Targeting Hypotheses (5)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TBK1-OPTN-NDP52 Phospho-Cascade Coordinates Multi-Organelle	0.772	neurodegeneration	How do different organelle-specific auto
TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimina	0.724	neurodegeneration	How do the seven novel ALS genes functio
OPTN/TBK1 mutations create selective vulnerability by blocki	0.670	neurodegeneration	What are the neuron-specific effects of
ALS-Linked OPTN/TBK1 Mutations Impair Phosphorylation Cascad	0.648	neurodegeneration	How do pathological stress granules in n
TBK1 Phosphorylation State Creates Phospho-Regulated Periphe	0.577	neurodegeneration	What determines the spatial organization

Mentioning Analyses (3)

Scientific analyses that reference this entity

Experiments (4)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Endothelium-specific TBK1 knockdown in atherosclerosis model	validation	atherosclerosis	0.900	endothelium-specific TBK1 knoc	proposed	N/A
TBK1-PAK1IP1-PAK1 signaling pathway analysis	exploratory	atherosclerosis	0.900	endothelial cells	proposed	N/A
LC-MS/Western blot analysis of TBK1 in atherosclerotic arteries	exploratory	atherosclerosis	0.800	mouse and human arteries with	proposed	N/A
GSK8612 treatment in atherosclerosis model	validation	atherosclerosis	0.800	atherosclerosis mouse model	proposed	N/A

Related Papers (10)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Restricting intracellular Salmonella proliferation by coordinating p-TBK1 mediat [PMID:40660474]	Li J, Yang Y, Ge Y, Zhang X, Liu H et al	Autophagy	2026
Aberrant STING signalling promotes endothelial dysfunction and neurovascular inj [PMID:41419617]	Qin X, Chen S, Sun Y, Ma Z, Niu C et al.	Diabetologia	2026
TBK1 orchestrates autophagy and endo-lysosomal pathways in human neurons. [PMID:41485128]	Mordes DA, Smeyers J	Autophagy	2026
Dynamic regulation of TBK1 lactylation shapes antiviral immune responses. [PMID:41530535]	Xie Y, Zhang Y, Peng W, Zhang L, Hu Z et	Cell Mol Immunol	2026
RIG-I Mediated Neuron-Specific IFN Type 1 Signaling in FUS-ALS Induces Neurodege [PMID:41603250]	Naumann M, Wierschin TM, Kretschmer S, D	Adv Sci (Weinh)	2026
BTK inhibition suppresses neuroinflammation and neurodegeneration in amyotrophic [PMID:41710977]	Liu Q, Zhang X, Wang L, Chen H, Wang G e	Brain	2026
Systematic Review: Porphyromonas gingivalis Outer Membrane Vesicles From Pathoge [PMID:41980468]	Li Z, Luo C, Wen P, Zou T, Jin Z et al.	Int Dent J	2026
TBK1 orchestrates autophagy and endo-lysosomal pathways in human neurons. [PMID:41485128]	Mordes DA, Smeyers J	Autophagy	2026
BTK inhibition suppresses neuroinflammation and neurodegeneration in amyotrophic [PMID:41710977]	Liu Q, Zhang X, Wang L, Chen H, Wang G,	Brain : a journal of neurology	2026
RIG-I Mediated Neuron-Specific IFN Type 1 Signaling in FUS-ALS Induces Neurodege [PMID:41603250]	Naumann M, Wierschin TM, Kretschmer S, D	Advanced science (Weinheim, Ba	2026

Debates (3)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning TBK1 in their description or question text

No additional research found

TBK1

Understanding Entity Pages

Summary

Wiki Pages (7)

TBK1-Mediated Neuroinflammation Hypothesis — Autophagy Failure and Innate Immune Dysregulation in FTD/ALS

TBK1 Protein

TBK1 Protein (TANK-Binding Kinase 1)

TBK1-Mediated Neuroinflammation Hypothesis — Impaired Autophagy and Innate Immune Dysregulation in FTD/ALS

TBK1 Gene

TBK1 Autophagy and Neuroinflammation ALS/FTD Causal Chain

Pathway Diagram

Outgoing (663)

Incoming (614)

Targeting Hypotheses (5)

Mentioning Analyses (3)

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

How do the seven novel ALS genes function in animal models to cause neurodegener

Senolytic therapy for age-related neurodegeneration

Experiments (4)

Related Papers (10)

Debates (3)

The authors explicitly state that the effects of these novel genes (MATR3, CHCHD

The study shows VCP-mutant astrocytes exhibit hypoxia response activation withou

Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP

Related Research

TBK1

Understanding Entity Pages

Summary

Wiki Pages (7)

TBK1-Mediated Neuroinflammation Hypothesis — Autophagy Failure and Innate Immune Dysregulation in FTD/ALS

TBK1 Protein

TBK1 Protein (TANK-Binding Kinase 1)

TBK1-Mediated Neuroinflammation Hypothesis — Impaired Autophagy and Innate Immune Dysregulation in FTD/ALS

TBK1 Gene

TBK1 Autophagy and Neuroinflammation ALS/FTD Causal Chain

TBK1 — TANK Binding Kinase 1

Pathway Diagram

Outgoing (663)

Incoming (614)

Targeting Hypotheses (5)

Mentioning Analyses (3)

What molecular mechanism causes VCP mutations to trigger aberrant HIF-1α activat

How do the seven novel ALS genes function in animal models to cause neurodegener

Senolytic therapy for age-related neurodegeneration

Experiments (4)

Related Papers (10)

Debates (3)

The authors explicitly state that the effects of these novel genes (MATR3, CHCHD

The study shows VCP-mutant astrocytes exhibit hypoxia response activation withou

Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP

Related Research