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.

1322Connections

8Hypotheses

4Analyses

50Outgoing

50Incoming

12Experiments

7Debates

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
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	Cross-Seeding Prevention Strategy Glial Neuroinflammatory Amplification by TDP-43 Pa Glycine-Rich Domain Competitive Inhibition (+5 more)
KG Connections	1284 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 (735)

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

Incoming (587)

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

Targeting Hypotheses (8)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
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
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
Cytosolic TDP-43 aggregation sequesters SNAP29 and syntaxin-	0.600	neurodegeneration	What are the neuron-specific effects of

Cryptic Exon Silencing Restoration	0.531	neurodegeneration	RNA binding protein dysregulation across
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

Mentioning Analyses (4)

Scientific analyses that reference this entity

Experiments (12)

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	proposed	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
s:** - Temporal analysis showing mitochondrial defects precede other p	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000

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
Targets and Gene Therapy of ALS (Part 1). [PMID:40362304]	Shiryaeva O, Tolochko C, Alekseeva T, Dy	Int J Mol Sci	2025	1
The genetics of amyotrophic lateral sclerosis. [PMID:38967083]	Nijs M, Van Damme P	Curr Opin Neurol	2024	1
TDP-43 regulates LC3ylation in neural tissue through ATG4B cryptic splicing inhi [PMID:39305312]	Torres P, Rico-Rios S, Ceron-Codorniu M,	Acta Neuropathol	2024	1
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
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A. [PMID:35197628]	Brown AL, Wilkins OG, Keuss MJ, Kargbo-H	Nature	2022	1
Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP- [PMID:28405022]	Becker LA, Huang B, Bieri G, Ma R, Knowl	Nature	2017	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
ALS-related proteinopathies: From TDP-43 to mitochondrial proteinopathies. [PMID:41570741]	Genin EC, Paquis-Flucklinger V	Current opinion in neurobiolog	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
Refolding-assisted purification of native full-length TDP-43 compatible with BSL [PMID:41692368]	Dehury S, Tiwari S, Los Rios P	Methods	2026	0
Small heat shock proteins HspB1 and HspB5 differentially alter the condensation [PMID:41854301]	Walker TB, Trowbridge JW, McMahon S, Mar	Protein Sci	2026	0

Debates (7)

Multi-agent debates referencing this entity

TARDBP

Understanding Entity Pages

Summary

Wiki Pages (5)

TARDBP — TAR DNA Binding Protein 43

TARDBP Protein (TDP-43)

TARDBP/TDP-43 Protein

ALS10 - Amyotrophic Lateral Sclerosis 10 (TARDBP)

TARDBP Mutations in Amyotrophic Lateral Sclerosis

Pathway Diagram

Outgoing (735)

Incoming (587)

Targeting Hypotheses (8)

Mentioning Analyses (4)

CRISPR-based therapeutic approaches for neurodegenerative diseases

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 (12)

Related Papers (20)

Debates (7)

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

Evaluate the potential of CRISPR/Cas9 and related gene editing technologies for