gene

TARDBP

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TARDBP: 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.

1254Connections

25Hypotheses

7Analyses

50Outgoing

50Incoming

11Experiments

10Debates

Summary

TARDBP is a gene implicated in neurodegeneration research. Key relationships include: associated with, activates, interacts with. Associated with AD, ALI, ALS. Connected to 534 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	TARDBP
Chromosome	1p36
Protein Type	Transcription Factor
Target Class	Transcription Factor
Function	RNA-binding and transcription regulation, challenging for small molecule targeting
Mechanism of Action	RNA-binding and transcription regulation, challenging for small molecule targeting
Subcellular Localization	</b></td><td>Nucleus (healthy), Cytoplasm (disease)</td></tr>
Druggability	Low (0.43)
Clinical Stage	Phase III
Molecular Weight	43 kDa
Amino Acids	4477 aa
Pathways	Apoptosis, Autophagy, Immune Response, Oxidative Stress, Tdp-43
UniProt ID	A0A087WYY0
GeneCards	TARDBP
Human Protein Atlas	TARDBP
Associated Diseases	AD, ALI, Als, ALS-FTD, Alzheimer
Known Drugs/Compounds	rapamycin, RAPAMYCIN, Transcribed Rnas
Interactions	ABCA1, AD, AIF1, ALS, ALS-CAUSING MUTATIONS, AMPK
SciDEX Target	View Target Profile (7 clinical trials)
SciDEX Hypotheses	TDP-43 RNA-proteostasis failure across ALS, FTD, a STMN2 Cryptic Exon Inclusion is the Earliest Loss- Cross-Seeding Prevention Strategy (+22 more)
KG Connections	1218 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — TARDBP Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

4BS2 — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q13148 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (5)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    A["SRPK1"] -->|"phosphorylates"| B["TARDBP/TDP-43"]
    C["PRMT1"] -->|"methylates"| B
    B -->|"binds RNA"| D["RNA Processing"]
    B -->|"regulates"| E["HNRNPA2B1"]
    B -->|"interacts"| F["NPM1"]
    D -->|"impaired"| G["Stress Granules"]
    G -->|"contains"| H["G3BP1"]
    B -->|"aggregates"| I["TDP-43 Proteinopathy"]
    J["PARP1"] -->|"modulates"| B
    K["HSPA1A"] -->|"chaperone activity"| B
    I -->|"leads to"| L["ALS/FTD"]
    I -->|"causes"| M["Neurodegeneration"]
    G -->|"dysfunction"| M

Outgoing (700)

Target	Relation	Type	Str
TARDBP	encodes	protein	0.00
TDP-43	associated_with	protein	1.00
CORTEX	associated_with	brain_region	1.00
FRONTOTEMPORAL DEMENTIA	associated_with	disease	1.00
DEMENTIA	associated_with	disease	1.00
NEURON	associated_with	cell_type	1.00
TDP43	expresses	protein	1.00
TAU	associated_with	protein	1.00
FTD	associated_with	disease	1.00
Loss Of Function	causes	phenotype	0.98
Frontotemporal Lobar Degeneration with TDP-43 Type C	implicated_in	disease	0.98
Tdp-43 Aggregation	involved_in	process	0.98
zygotic splicing activation	associated_with	process	0.95
nuclear speckle assembly	regulates	process	0.95
RNA splicing	regulates	process	0.95
Ubiquitination	involved_in	process	0.95
Lc3Ylation	regulates	process	0.95
UNC13A	regulates	gene	0.95
ALS	associated_with	disease	0.95
Frontotemporal Lobar Degeneration	associated_with	disease	0.95
Intra-Condensate Demixing	involved_in	process	0.95
Tdp-43 Proteinopathy	involved_in	disease	0.95
Mitochondrial Dna	causes	compound	0.95
Nuclear Condensation	mediates	mechanism	0.95
STMN2	regulates	gene	0.95
NEAT1	regulates	gene	0.95
ALS	biomarker_for	disease	0.95
ATG4B	regulates	gene	0.95
Ftld-Tdp	component_of	disease	0.95
FTD	causes	disease	0.95
Amyotrophic Lateral Sclerosis	associated_with	disease	0.95
Zygotic Splicing Activation	regulates	process	0.95
Nuclear Speckle Assembly	activates	process	0.95
mitochondrial DNA	associated_with	compound	0.95
biomolecular condensates	associated_with	process	0.95
liquid-liquid phase separation	involved_in	process	0.95
neurodegeneration	causes	disease	0.95
ALS-FTD	associated_with	disease	0.95
Nuclear Speckle Assembly	regulates	process	0.95
HDGFL2	regulates	protein	0.93
FTLD-TDP Type C	associated_with	disease	0.93
FTLD-TDP C	associated_with	disease	0.92
protein aggregation	promotes	process	0.92
Behavior Variant Ftd	biomarker_for	disease	0.92
UNC13A	drives	gene	0.92
Cryptic Splicing	mediates	process	0.92
Motor Neuron	expressed_in	cell_type	0.90
Unc13A	modulates	protein	0.90
liquid-liquid phase separation	mediates	process	0.90
mis-splicing	mediates	process	0.90

Incoming (554)

Source	Relation	Type	Str
TARDBP	encodes	gene	0.00
ALS	associated_with	gene	1.00
AMYLOID	associated_with	protein	1.00
ALZHEIMER'S DISEASE	associated_with	disease	1.00
AUTOPHAGY	associated_with	gene	1.00
FUS	associated_with	gene	1.00
SOD1	associated_with	gene	1.00
MAPK/ERK	phosphorylates	pathway	0.95
Extracellular Vesicles	transports	biomarker	0.95
Alternative Splicing	regulates	process	0.95
Pedv N Protein	degrades	protein	0.90
YWHAQ	binds	protein	0.90
Stress	activates	process	0.90
Heat Shock Response	phosphorylates	process	0.90
Tdp-43 Aggregates	associated_with	protein	0.90
Up-Concentration In Stress Granules	mediates	process	0.90
h-eea667a9	targets	hypothesis	0.90
h-10b5bf6f	targets	hypothesis	0.90
CASP2	modulates	protein	0.90
h-47ab2be5	targets	hypothesis	0.90
Oxidative Stress	promotes	process	0.90
h-7e846ceb	targets	hypothesis	0.90
h-var-a0933e666d	targets_gene	hypothesis	0.90
h-4fabd9ce	targets	hypothesis	0.90
ATXN2	suppresses	gene	0.90
h-7693c291	targets	hypothesis	0.90
Ubiquitination	promotes	process	0.90
h-cross-synth-tdp43-rna-proteostasis	proposes_shared_mechanism	hypothesis	0.86
Frontotemporal Dementia	associated_with	disease	0.85
CasRx	inhibits	protein	0.85
Nuclear Condensation	inhibits	mechanism	0.85
PARKINSON'S DISEASE	associated_with	gene	0.82
Als-Linked Mutations	modulates	biomarker	0.80
TAR	regulates	gene	0.75
NF-KB	associated_with	protein	0.74
MAPT	expressed_in	gene	0.70
BACE1	activates	gene	0.70
APP	activates	gene	0.70
FRONTOTEMPORAL DEMENTIA	causes	disease	0.70
ATG5	regulates	gene	0.70
ABCA1	inhibits	gene	0.70
FUS	disrupts	gene	0.70
FUS	activates	gene	0.70
FTD	associated_with	disease	0.70
MOTOR NEURON	activates	cell_type	0.70
STING	expresses	gene	0.70
STING	associated_with	gene	0.70
NRF2	interacts_with	gene	0.70
rapamycin	targets	drug	0.70
OPTN	associated_with	gene	0.70

Targeting Hypotheses (25)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TDP-43 RNA-proteostasis failure across ALS, FTD, and AD/LATE	0.828	multi	Cross-disease neurodegeneration mechanis
STMN2 Cryptic Exon Inclusion is the Earliest Loss-of-Functio	0.760	als	Causal Sequence of TDP-43 Nuclear Cleara
Cross-Seeding Prevention Strategy	0.689	neurodegeneration	RNA binding protein dysregulation across
Glial Neuroinflammatory Amplification by TDP-43 Pathology	0.680	neurodegeneration	What mechanisms underlie TDP-43's contri
TDP-43 Liquid-Liquid Phase Separation Dominance in Stress Gr	0.650	alzheimers	-

Glycine-Rich Domain Competitive Inhibition	0.640	neurodegeneration	TDP-43 phase separation therapeutics for
Synaptic RNA Metabolism Dysregulation	0.620	neurodegeneration	What mechanisms underlie TDP-43's contri
TDP-43 LLPS and proteostasis dysregulation in ALS/FTD	0.600	neurodegeneration	Test
Cytosolic TDP-43 aggregation sequesters SNAP29 and syntaxin-	0.600	neurodegeneration	What are the neuron-specific effects of
Small-Molecule Modulation of TDP-43 Liquid-Liquid Phase Sepa	0.565	neurodegeneration	Test
TDP-43 Co-pathology Subtype Identified Through Motor Neuron	0.564	neurodegeneration	Methodology challenge: dataset 'Allen Br
Cryptic Exon Silencing Restoration	0.531	neurodegeneration	RNA binding protein dysregulation across
Rational design of small molecules targeting TDP-43 liquid-t	0.510	neurodegeneration	Test
G3BP1-TDP-43 Cross-Seeding Drives Co-Aggregation That Prion-	0.490	neurodegeneration	How do disease-associated mutations in G
RNA-Binding Competition Therapy for TDP-43 Cross-Seeding	0.465	neurodegeneration	Protein aggregation cross-seeding across
RNA Granule Phase Separation as Transient Cross-Seeding Hub	0.455	neurodegeneration	Protein aggregation cross-seeding across
RNA Splicing Corrector Compounds	0.000	-	RNA binding protein dysregulation across
C-Terminal Frameshift Protection via RNA-Guided Editing	0.000	-	TDP-43 phase separation therapeutics for
Nuclear Import Receptor Enhancers as Phase Separation Modula	0.000	-	TDP-43 phase separation therapeutics for
ATP-Mimetic Phase Separation Modulators	0.000	-	TDP-43 phase separation therapeutics for
Bi-functional Nuclear Trafficking-Phase Separation Modulator	0.000	-	TDP-43 phase separation therapeutics for
Nuclear Import Receptor Enhancers	0.000	-	TDP-43 phase separation therapeutics for
Phase Transition Kinetics Modulators	0.000	-	TDP-43 phase separation therapeutics for
Membraneless Organelle Stabilizers Targeting Low-Complexity	0.000	-	TDP-43 phase separation therapeutics for
Prion-Like Domain Stabilizers via Aromatic Interaction Modul	0.000	-	TDP-43 phase separation therapeutics for

Mentioning Analyses (7)

Scientific analyses that reference this entity

Cross-disease neurodegeneration mechanism synthesis

neurodegeneration | 2026-04-28 | 17 hypotheses Top: 0.828

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.387

How can subcellular compartmentalization defects be measured as biomarkers in li

neuroscience | 2026-04-10 | 5 hypotheses Top: 0.724

What are the neuron-specific effects of ALS-causing mutations on autophagy machi

neurodegeneration | 2026-04-08 | 4 hypotheses Top: 0.720

RNA binding protein dysregulation across ALS FTD and AD

neurodegeneration | 2026-04-01 | 13 hypotheses Top: 0.720

Experiments (11)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
TDP-43 mitochondrial invasion and DNA release via mPTP	exploratory	amyotrophic lateral sclerosis	0.900	0.00	cultured cells	proposed	N/A
TDP-43 mutant mouse model cGAS/STING pathway analysis	validation	amyotrophic lateral sclerosis	0.900	0.00	TDP-43 mutant mice	proposed	N/A
TDP-43 mitochondrial invasion and mtDNA release in iPSC motor neurons	exploratory	Amyotrophic Lateral Sclerosis	0.900	0.00	iPSC-derived motor neurons	proposed	N/A
cGAS/STING pathway validation in TDP-43 mutant mice	validation	Amyotrophic Lateral Sclerosis	0.850	0.00	TDP-43 mutant mice	proposed	N/A
cGAMP biomarker analysis in ALS patient spinal cord samples	exploratory	Amyotrophic Lateral Sclerosis	0.800	0.00	Human ALS patient spinal cord	proposed	N/A
TDP-43 pathology prevalence and distribution in AD cases	exploratory	Alzheimer's disease	0.800	0.00	human postmortem brain tissue	proposed	N/A
Cognitive impact of TDP-43 pathology in AD patients	clinical	Alzheimer's disease	0.700	0.00	human patients	completed	N/A
Proposed experiment from debate on TDP-43 undergoes liquid-liquid phas	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
s:** - Single-cell RNA-seq to measure editing efficiency across differ	falsification	ALS	0.400	0.50	cell_line	proposed	$150,000
Alpha-Synuclein SAA Kinetics Study — Biological Staging Backbone for P	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
ALS Progression Rate Heterogeneity — mechanism and biomarker predictor	clinical	ALS	0.400	0.50	human	proposed	$6,550,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Autophagy and ALS: mechanistic insights and therapeutic implications. [PMID:34057020]	Chua JP, De Calbiac H, Kabashi E, Barmad	Autophagy	2022	2
TDP-43 Pathology in Alzheimer's Disease. [PMID:34930382]	Meneses A, Koga S, O'Leary J, Dickson DW	Mol Neurodegener	2021	2
Protein transmission in neurodegenerative disease. [PMID:32203399]	Peng C, Trojanowski JQ, Lee VM	Nat Rev Neurol	2020	2
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS [PMID:33031745]	Yu CH, Davidson S, Harapas CR, Hilton JB	Cell	2020	2
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of [PMID:30335591]	Rusmini P, Cortese K, Crippa V, Cristofa	Autophagy	2019	2
N protein of PEDV plays chess game with host proteins by selective autophagy. [PMID:36861818]	Zhai X, Kong N, Zhang Y, Song Y, Qin W,	Autophagy	2023	1
PIKFYVE inhibition mitigates disease in models of diverse forms of ALS. [PMID:36754049]	Hung ST, Linares GR, Chang WH, Eoh Y, Kr	Cell	2023	1
Selective Silencing of TDP-43 P. G376D Mutation Reverses Key Amyotrophic Lateral [PMID:41897327]	Romano R, Ruotolo G, Perrone F, Tomasell	Biomolecules	2026	0
Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Protein [PMID:41900026]	Jamerlan A, Hulme J	Molecules (Basel, Switzerland)	2026	0
Axonal transport impairment as an upstream mechanism in amyotrophic lateral scle [PMID:41890591]	Gabbay U	Frontiers in neuroscience	2026	0
Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA- [PMID:41512823]	["Guo L", "Mann J", "Mauna J", "Copley K	Molecular cell	2026	0
Role of Alpha-Synuclein in Frontotemporal Dementia: Narrative Review. [PMID:41827903]	Bougea A	Cells	2026	0
The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study [PMID:41883703]	Nassan M, Ayala I, Sloan J, Bonfitto A,	Neurology. Genetics	2026	0
Excitotoxicity in amyotrophic lateral sclerosis: a key pathogenic mechanism. [PMID:41890274]	Silva-Hucha S, Hernández RG, Baena-López	Brain communications	2026	0
Direct observation and quantification of single nanocondensates of the low compl [PMID:41654570]	["Houx J", "Cussac J", "Copie T", "Gambi	Nature communications	2026	0
Antisense oligonucleotide targeting TARDBP-EGFR splicing axis inhibits progressi [PMID:41540015]	Ni N, Wang M, Yuan Z, Zhang L, Cai J, Du	International journal of oral	2026	0
Biofluid biomarkers in Alzheimer's disease and other neurodegenerative dementias [PMID:41639575]	Zetterberg H, Bendlin BB	Nature	2026	0
Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexi [PMID:41690263]	["Jami K", "Corbett K", "Farb D", "Osumi	Biophysical chemistry	2026	0
Elucidation of Molecular Mechanisms of Lipid-Altered Cytotoxicity of TDP-43 Fibr [PMID:41609580]	["Purvinsh Y", "Matveyenka M", "Kurouski	ACS chemical neuroscience	2026	0
Correction: Antisense oligonucleotide targeting TARDBP-EGFR splicing axis inhibi [PMID:41775718]	Ni Nan; Wang Moxu; Yuan Zhiran; Zhang Le	International journal of oral	2026	0

Debates (10)

Multi-agent debates referencing this entity

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

closed · Rounds: 4 · Score: 0.72 · 2026-04-28

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

completed · Rounds: 5 · Score: 0.50 · 2026-04-25

While ALS-causing mutations impair autophagy factors, the neuron-specific effect

closed · Rounds: 4 · Score: 0.81 · 2026-04-21

The clinical trialist identified this as a 'fatal clinical flaw' - no validated

closed · Rounds: 4 · Score: 0.65 · 2026-04-21

Protein aggregation cross-seeding across neurodegenerative diseases?

closed · Rounds: 4 · Score: 0.70 · 2026-04-12

RNA binding protein dysregulation across ALS FTD and AD

closed · Rounds: 4 · Score: 0.72 · 2026-04-12

TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small

closed · Rounds: 6 · Score: 0.84 · 2026-04-12

TDP-43 phase separation therapeutics for ALS-FTD

closed · Rounds: 4 · Score: 0.95 · 2026-04-11

Analysis question not specified

closed · Rounds: 4 · Score: 0.53 · 2026-04-06

RNA binding protein dysregulation across ALS FTD and AD

closed · Rounds: 4 · Score: 0.88 · 2026-04-06

Related Research

Hypotheses and analyses mentioning TARDBP in their description or question text

TARDBP

Understanding Entity Pages

Summary

Wiki Pages (5)

TARDBP Protein (TDP-43)

TARDBP — TAR DNA Binding Protein 43

TARDBP/TDP-43 Protein

ALS10 - Amyotrophic Lateral Sclerosis 10 (TARDBP)

TARDBP Mutations in Amyotrophic Lateral Sclerosis

Pathway Diagram

Outgoing (700)

Incoming (554)

Targeting Hypotheses (25)

Mentioning Analyses (7)

Cross-disease neurodegeneration mechanism synthesis

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

How can subcellular compartmentalization defects be measured as biomarkers in li

What are the neuron-specific effects of ALS-causing mutations on autophagy machi

RNA binding protein dysregulation across ALS FTD and AD

TDP-43 phase separation therapeutics for ALS-FTD

Protein aggregation cross-seeding across neurodegenerative diseases

Experiments (11)

Related Papers (20)

Debates (10)

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

While ALS-causing mutations impair autophagy factors, the neuron-specific effect

The clinical trialist identified this as a 'fatal clinical flaw' - no validated

Protein aggregation cross-seeding across neurodegenerative diseases?

RNA binding protein dysregulation across ALS FTD and AD

TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small

TDP-43 phase separation therapeutics for ALS-FTD

Analysis question not specified

RNA binding protein dysregulation across ALS FTD and AD

Related Research

Glycine-Rich Domain Competitive Inhibition

Synaptic RNA Metabolism Dysregulation

TDP-43 LLPS and proteostasis dysregulation in ALS/FTD

Cytosolic TDP-43 aggregation sequesters SNAP29 and syntaxin-17, blocking autopha

Small-Molecule Modulation of TDP-43 Liquid-Liquid Phase Separation for ALS/FTD

TDP-43 Co-pathology Subtype Identified Through Motor Neuron Transcriptomics

Cryptic Exon Silencing Restoration

Rational design of small molecules targeting TDP-43 liquid-to-solid phase transi

G3BP1-TDP-43 Cross-Seeding Drives Co-Aggregation That Prion-Spreads Across Neura

RNA-Binding Competition Therapy for TDP-43 Cross-Seeding

RNA Granule Phase Separation as Transient Cross-Seeding Hub

RNA Splicing Corrector Compounds

C-Terminal Frameshift Protection via RNA-Guided Editing

Nuclear Import Receptor Enhancers as Phase Separation Modulators

ATP-Mimetic Phase Separation Modulators