gene

TF

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TF: 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.

29Connections

30Hypotheses

7Analyses

14Outgoing

15Incoming

18Experiments

7Debates

Summary

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🧬 Gene Info

Gene Symbol	TF
Full Name	Transferrin
Chromosome	3q22.1
Function	is a single-chain glycoprotein folded into two homologous lobes (N-lobe and C-lobe), each containing a single iron-binding site.
Molecular Weight	80 kDa
Pathways	Iron uptake
UniProt ID	P02787
NCBI Gene ID	7018
OMIM	190000
GeneCards	TF
Human Protein Atlas	TF
TfR1 dysregulation	TfR1 expression is altered in AD neurons, potentially increasing iron uptake into vulnerable cells.[@zecca2004]
Associated Diseases	neurodegeneration
Interactions	MYC, OCT4, TP53, WNT
KG Connections	29 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: TF — AlphaFold P02787 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    TF["TF"]
    Iron["Iron"]
    TFRC["TFRC"]
    TFR2["TFR2"]
    Chronic_Cerebral_Hypoperfusion["Chronic Cerebral Hypoperfusion"]
    neurodegeneration["neurodegeneration"]

    TF -->|"binds"| Iron
    TFRC -->|"binds"| TF
    TFR2 -->|"binds"| TF
    Chronic_Cerebral_Hypoperfusion -->|"upregulates"| TF
    TF -->|"implicated in"| neurodegeneration

    style TF fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px,color:#fff
    style Iron fill:#1a1a2e,stroke:#888,stroke-width:2px,color:#fff
    style TFRC fill:#1a1a2e,stroke:#888,stroke-width:2px,color:#fff
    style TFR2 fill:#1a1a2e,stroke:#888,stroke-width:2px,color:#fff
    style Chronic_Cerebral_Hypoperfusion fill:#1a1a2e,stroke:#888,stroke-width:2px,color:#fff
    style neurodegeneration fill:#1a1a2e,stroke:#888,stroke-width:2px,color:#fff

Outgoing (14)

Target	Relation	Type	Str
Iron	binds	compound	0.95
Iron uptake	involved_in	process	0.90
TFR2	upregulates	protein	0.80
oxidative stress response	participates_in	pathway	0.70
pyroptosis	participates_in	pathway	0.60
ubiquitin-proteasome	participates_in	pathway	0.60
microglia	expressed_in	cell_type	0.60
astrocytes	expressed_in	cell_type	0.60
WNT	inhibits	gene	0.60
Alzheimer's disease	inhibits	disease	0.60
NF-kB signaling	participates_in	pathway	0.60
TP53	inhibits	gene	0.60
TXNIP	regulates	gene	0.60
neurons	expressed_in	cell_type	0.55

Incoming (15)

Source	Relation	Type	Str
Chronic Cerebral Hypoperfusion	upregulates	process	0.85
DNA	co_expressed_with	gene	0.60
MYC	inhibits	gene	0.60
SPI1	regulates	gene	0.60
OCT4	activates	gene	0.60
FOXO	regulates	gene	0.60
APOE	regulates	gene	0.60
FOS	regulates	gene	0.60
JUN	regulates	gene	0.60
CCND1	regulates	gene	0.60
MYH9	regulates	gene	0.60
AXIN1	regulates	gene	0.60
MYO1C	regulates	gene	0.60
RHEB	regulates	gene	0.60
SOCS3	regulates	gene	0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TFEB Nuclear Translocation to Reset Lysosomal-Hypoxia Axis	0.779	neurodegeneration	What molecular mechanism causes VCP muta
GBA1 Loss Triggers a TFEB-to-TFE3 Compensatory Switch in A9	0.750	neurodegeneration	-
TFEB/TFE3 Parallel Activation Drives Coordinated Organelle C	0.727	neurodegeneration	How do different organelle-specific auto
TFAM overexpression creates mitochondrial donor-recipient gr	0.725	neurodegeneration	Mitochondrial transfer between astrocyte
TFEB-Independent Autophagy Bypass	0.697	neurodegeneration	Does TFEB dysfunction cause neurodegener

TFEB-Dependent Lysosome Biogenesis	0.690	neurodegeneration	How does controlled lysosomal membrane p
TFEB-mediated transcriptional upregulation of lysosomal gene	0.679	neuroscience	Lysosomal dysfunction and cathepsin leak
Cell-Type Specific TFEB Modulation	0.677	neurodegeneration	Does TFEB dysfunction cause neurodegener
mTORC1 displacement from lysosomal surface enables calcineur	0.650	neurodegeneration	What determines the specificity of calci
SNCA Oligomers Sequester TFEB Phosphatases to Create a Phosp	0.650	neurodegeneration	-
Mitochondrial SPM Synthesis Platform Engineering	0.647	neurodegeneration	Neuroinflammation resolution mechanisms
mTORC1 Displacement from Lysosomal Membrane Enables TFEB Nuc	0.640	neurodegeneration	-
Caloric Restriction Mimetic Combination Therapy (Metformin +	0.640	neurodegeneration	-
G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclu	0.633	neurodegeneration	What determines the spatial organization
Multi-Modal CRISPR Platform for Simultaneous Editing and Mon	0.629	neurodegeneration	CRISPR-based therapeutic approaches for
ATF4-DDIT3 stress signaling indirectly represses MAPT transc	0.624	neurodegeneration	Which specific transcription factors med
TFEB-PGC1α Mitochondrial-Lysosomal Decoupling	0.622	neurodegeneration	Gene expression changes in aging mouse b
Optogenetic viral vector delivery via tFUS-mediated blood-br	0.622	Alzheimer's disease	Circuit-level neural dynamics in neurode
Lysosomal pH Restoration Upstream of TFEB	0.619	neurodegeneration	Does TFEB dysfunction cause neurodegener
Temporal TFEB Modulation Therapy	0.609	neurodegeneration	Does TFEB dysfunction cause neurodegener
Impaired TFEB/TFE3 Nuclear Translocation Due to mTORC1 Hyper	0.603	neurodegeneration	What mechanisms underlie neuronal resist
Selective TFEB Cofactor Enhancement	0.602	neurodegeneration	Does TFEB dysfunction cause neurodegener
TFEB Activation to Restore Lysosomal Biogenesis in Aged Syna	0.591	proteomics	Quantitative proteomics of the aging syn
PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5	0.584	neurodegeneration	How does PIKFYVE inhibition activate unc
TFEB Nuclear Translocation Clears α-Synuclein via Autophagy-	0.580	neurodegeneration	Test Preregistration Analysis
Synergistic enhancement of autophagy and lysosomal biogenesi	0.565	neuroscience	Lysosomal dysfunction and cathepsin leak
TFEB Activation Clears Tau-Loaded Endolysosomal Compartments	0.560	neurodegeneration	Investigate prion-like spreading of tau
HBOT (2.0 ATA, 60 min) activates TFEB-mediated autophagy-lys	0.560	neurodegeneration	What are the optimal oxygen pressure, du
YWHAG-Mediated TFEB Subcellular Targeting	0.549	neurodegeneration	Does TFEB dysfunction cause neurodegener
CNTF-JAK/STAT3 Reprogramming of Trained Microglia to Neuropr	0.547	neuroinflammation	What specific astrocyte-derived factors

Mentioning Analyses (7)

Scientific analyses that reference this entity

What validated biomarkers can determine optimal TFEB activity windows during dis

neurodegeneration | 2026-04-11 | 0 hypotheses

Does TFEB activation directly restore mutant GBA enzyme activity or only enhance

molecular biology | 2026-04-11 | 0 hypotheses

Does TFEB dysfunction causally drive neurodegeneration or represent compensatory

molecular biology | 2026-04-10 | 0 hypotheses

Why do structurally diverse sugars (trehalose, melibiose, lactulose) produce ide

neurodegeneration | 2026-04-08 | 3 hypotheses Top: 0.470

What determines the specificity of calcium-dependent PPP3/calcineurin activation

neurodegeneration | 2026-04-07 | 4 hypotheses Top: 0.705

Experiments (18)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
IRI-AKI mouse model with mtROS inhibition	validation	ischemic acute kidney injury	0.900	0.00	IRI-AKI mice	proposed	N/A
mtROS effects on TFAM and mtDNA in HK2 cells	exploratory	acute kidney injury	0.900	0.00	HK2 cells	proposed	N/A
Transcriptome sequencing of cardiac fibroblasts in TFEB overexpressing	exploratory	myocardial infarction	0.900	0.00	R26-LSL-TFEB+/+; Acta2-cre mic	proposed	N/A
Trehalose-induced lysosomal changes and TFEB activation	exploratory	motoneuron degeneration	0.900	0.00	NSC34 neuroblastoma x spinal c	proposed	N/A
Trehalose-induced lysosomal membrane permeabilization and TFEB activat	exploratory	motoneuron degeneration	0.900	0.00	NSC34 neuroblastoma cells	proposed	N/A
TFEB silencing and misfolded protein degradation	exploratory	motoneuron degeneration	0.880	0.00	NSC34 neuroblastoma x spinal c	proposed	N/A
Protein expression analysis and cell migration assays in cardiac fibro	exploratory	cardiac fibrosis	0.880	0.00	primary cardiac fibroblasts fr	proposed	N/A
TFAM knockdown functional analysis	exploratory	acute kidney injury	0.850	0.00	HK2 cells	proposed	N/A
Functional validation of trehalose effects on misfolded protein cleara	exploratory	motoneuron degeneration diseas	0.850	0.00	cell models expressing misfold	proposed	N/A
ChIP-qPCR validation of TFEB binding to Thbs1 promoter	exploratory	cardiac fibrosis	0.850	0.00	mouse cardiac fibroblasts	proposed	N/A
Trehalose analog testing for autophagy induction	exploratory	motoneuron degeneration	0.820	0.00	NSC34 neuroblastoma x spinal c	proposed	N/A
TFAM and mtDNA analysis in AKI patients	clinical	acute kidney injury	0.800	0.00	human patients	proposed	N/A
s:** - Test MCU overexpression specifically in layer II neurons in hea	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$200,000
Proposed experiment from debate on Mitochondrial transfer between astr	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Selective Vulnerability of Dopaminergic Neurons — Mechanism and Protec	validation	Neurodegeneration	0.400	0.50	cell_line	proposed	$160,000
Exercise-BDNF-Mitophagy Biomarker Study in PD	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Ferroptosis Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
GLP-1 Agonist Neuroprotection Mechanism in PD	clinical	Parkinson's Disease	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
Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy t [PMID:37651673]	Deng Z, He M, Hu H, Zhang W, Zhang Y, Ge	Autophagy	2024	1
TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic [PMID:38783142]	Liu H, Zhen C, Xie J, Luo Z, Zeng L, Zha	Nat Cell Biol	2024	1
Mitochondrial-derived damage-associated molecular patterns amplify neuroinflamma [PMID:35233090]	Lin MM, Liu N, Qin ZH, Wang Y	Acta Pharmacol Sin	2022	1
Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic [PMID:33408785]	Zhao M, Wang Y, Li L, Liu S, Wang C, Yua	Theranostics	2021	1
Mitochondrial DNA copy number in human disease: the more the better? [PMID:33314045]	Filograna R, Mennuni M, Alsina D, Larsso	FEBS Lett	2021	1
Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death. [PMID:32186434]	Li C, Zhang Y, Liu J, Kang R, Klionsky D	Autophagy	2021	1
Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Protein [PMID:41900026]	Jamerlan A, Hulme J	Molecules (Basel, Switzerland)	2026	0
Butyrate extends health and lifespan in mice with mitochondrial deficiency. [PMID:41826362]	["Gaband\u00e9-Rodr\u00edguez E", "G\u00	Nature communications	2026	0
Vav-iCre-Mediated Deletion of TFAM Is Not Recoverable and Is Consistent with Emb [PMID:41898789]	["Ghosh R", "Shakur E", "Yousefzadeh M"]	Genes	2026	0
NRIP1 co-activates nuclear translocated FOXO3 to upregulate TFAM expression and [PMID:41888517]	["Zha Y", "Huang H", "Liu Y", "Wan M", "	Cell death discovery	2026	0
miR-137-5p-Loaded Milk-Derived Small Extracellular Vesicles Modulate Oxidative S [PMID:41754992]	["G\u00f6n\u00fcll\u00fc S", "Ayd\u0131n	Pharmaceutics	2026	0
Mammalian lipophagy: process and function. [PMID:41681129]	Zhao R, Dai E, Kang R, Liu J, Klionsky D	Autophagy	2026	0
Ginseng stem and leaf saponins attenuates pulmonary fibrosis by regulating TFAM- [PMID:41911987]	Chen Y, Hu L, Fu Q, Chen H, Jiang Z, Li	Journal of ethnopharmacology	2026	0
PSAT1 inhibits mTORC1 activation by preventing Rag heterodimer formation in lung [PMID:40702660]	Liu Y, Cheng Z, Zhang J, Zhang Y, Zhao T	Autophagy	2026	0
Electroacupuncture regulates neuronal ferroptosis and ferritinophagy through lys [PMID:41272418]	Tang B, Xu X, Zhao W, Zhou Q, Du G et al	J Cereb Blood Flow Metab	2026	0
Nanocarrier-enhanced simvastatin modulates AMPK-ULK1 pathway and oxidative stres [PMID:41314452]	Afify AM, El-Sayed EK, Ismail A, Nofal S	Eur J Pharmacol	2026	0
Macrophage PD-1 regulates energy expenditure and metabolic dysfunction under imm [PMID:41380676]	Wu MM, Yang YC, Hu ZQ, Chang JY, Xiao H	Cell Metab	2026	0
Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 [PMID:41400694]	Jacqmin T, Gilis F, Albert M, Gaussin JF	J Cell Biol	2026	0
Endothelial Transcription Factor EB Protects Against Doxorubicin-Induced Endothe [PMID:41410033]	Du W, Ringer M, Desai D, Khandakar GI, T	Circulation	2026	0
Proteotoxic stress triggers TFEB- and TFE3-mediated autophagy and lysosomal biog [PMID:41450115]	Zhu Z, Yang J, Montefusco S, Xia S, Ou J	Autophagy	2026	0

Debates (7)

Multi-agent debates referencing this entity

The study shows trehalose causes lysosomal membrane permeabilization (LMP) that

closed · Rounds: 4 · Score: 0.61 · 2026-04-21

While the study establishes that trehalose-induced lysosomal permeabilization ac

closed · Rounds: 4 · Score: 0.73 · 2026-04-21

The finding that trehalase-resistant analogs and other disaccharides mimic treha

closed · Rounds: 4 · Score: 0.60 · 2026-04-21

The debate identified this as a critical mechanistic gap - TFEB may increase lys

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

The core causation versus correlation debate remains unresolved despite being ce

closed · Rounds: 4 · Score: 0.50 · 2026-04-20

The debate proposed temporal TFEB modulation but identified no validated biomark

closed · Rounds: 4 · Score: 1.00 · 2026-04-20

The debate highlighted TFEB's role in mitochondrial-lysosomal coupling but could

closed · Rounds: 4 · Score: 0.95 · 2026-04-03

Related Research

Hypotheses and analyses mentioning TF in their description or question text

TFEB-Dependent Lysosome Biogenesis

Score: 0.690 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The transcription factor EB (TFEB) and its closely related family member TFE3 rep

TFEB-mediated transcriptional upregulation of lysosomal genes as a therapeutic s

Score: 0.679 · neuroscience · 2026-04-22

**Molecular Mechanism and Rationale** The transcription factor EB (TFEB) represents a master regulatory node in cellula

Cell-Type Specific TFEB Modulation

Score: 0.677 · neurodegeneration · 2026-04-04

## Mechanistic Overview Cell-Type Specific TFEB Modulation starts from the claim that modulating TFEB within the disease

mTORC1 displacement from lysosomal surface enables calcineurin access to TFEB

Score: 0.650 · neurodegeneration · 2026-04-21

## Mechanistic Overview mTORC1 displacement from lysosomal surface enables calcineurin access to TFEB starts from the cl

Mitochondrial SPM Synthesis Platform Engineering

Score: 0.647 · neurodegeneration · 2026-04-02

## Mechanistic Overview Mitochondrial SPM Synthesis Platform Engineering starts from the claim that modulating ALOX5 wit

G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclusion Zone for Autoph

Score: 0.633 · neurodegeneration · 2026-04-21

## Mechanistic Overview G3BP1 NTF2L Domain-Mediated mRNP Scaffold Creates Core Exclusion Zone for Autophagy Receptors st

Multi-Modal CRISPR Platform for Simultaneous Editing and Monitoring

Score: 0.629 · neurodegeneration · 2026-04-02

## Mechanistic Overview Multi-Modal CRISPR Platform for Simultaneous Editing and Monitoring starts from the claim that m

ATF4-DDIT3 stress signaling indirectly represses MAPT transcription during prote

Score: 0.624 · neurodegeneration · 2026-04-25

Integrated stress response factors redirect transcription and chromatin regulation away from tau expression during acute

TFEB-PGC1α Mitochondrial-Lysosomal Decoupling

Score: 0.622 · neurodegeneration · 2026-04-02

## Mechanistic Overview TFEB-PGC1α Mitochondrial-Lysosomal Decoupling starts from the claim that modulating TFEB within

Optogenetic viral vector delivery via tFUS-mediated blood-brain barrier opening

Score: 0.622 · Alzheimer's disease · 2026-04-07

## Mechanistic Overview Optogenetic viral vector delivery via tFUS-mediated blood-brain barrier opening to restore hippo

Lysosomal pH Restoration Upstream of TFEB

Score: 0.619 · neurodegeneration · 2026-04-04

## Mechanistic Overview Lysosomal pH Restoration Upstream of TFEB starts from the claim that modulating ATP6V1A within t

Temporal TFEB Modulation Therapy

Score: 0.609 · neurodegeneration · 2026-04-04

## Mechanistic Overview Temporal TFEB Modulation Therapy starts from the claim that modulating TFEB within the disease c

TF

Understanding Entity Pages

Summary

Wiki Pages (21)

TF

NTF4 Protein

CNTF Signaling Pathway in Neurodegeneration

CNTFR Gene

TFAM Gene

ATF3 Protein

Metabolic-Energetic Restoration: GLP-1 + TFEB Activator Combination

Section 244: Advanced Autophagy Induction and TFEB Activation in CBS/PSP

NTF5 — Neurotrophin 5

TFG Protein

GTF2H4 (General Transcription Factor IIH Subunit 4)

TFRC

Mitophagy Gate Therapy: PINK1/Parkin + TFEB Priming

TFEB Autophagy Pathway

ATF6 - Activating Transcription Factor 6

TFB1M — Mitochondrial Transcription Factor B1

GTF2H5 — General Transcription Factor IIH Subunit 5 (TTDA)

GTF2H6

TFEB Signaling in Neurodegeneration

MITF Gene — Microphthalmia-Associated Transcription Factor

Activating Transcription Factor 4 (ATF4)