gene

TFE3

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TFE3: 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.

610Connections

4Hypotheses

2Analyses

50Outgoing

50Incoming

0Experiments

2Debates

Summary

TFE3 is a gene implicated in neurodegeneration research. Key relationships include: interacts with, activates, regulates. Associated with ALS, Aging, Als. Connected to 302 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	TFE3
Function	is a member of the MiT/TFE family of basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors, alongside TFEB, MITF, and TFEC.
Primary Expression	neurons, microglia, astrocytes, and oligodendrocytes - Double
Molecular Weight	59.5 kDa
Amino Acids	575 aa
Pathways	mTOR, mtor
Ensembl ID	ENSG00000068323
GeneCards	TFE3
Human Protein Atlas	TFE3
Lysosomal hydrolases	CTSD, CTSB, CTSL, HEXA, HEXB, GLA
Lysosomal membrane proteins	LAMP1, LAMP2, MCOLN1, ATP6V0D1, ATP6V1H
Autophagy regulators	BECN1, ATG9A, ATG16L1, WIPI1, ULK1
Lipid catabolism	PPARGC1A, LIPA, ASAH1
Macroautophagy	Upregulation of ATG genes for autophagosome formation
Chaperone-mediated autophagy (CMA)	Induction of LAMP2A and HSC70
Associated Diseases	ALS, Alzheimer, Kidney Cancer, Multiple Sclerosis, neurodegeneration, Parkinson
Known Drugs/Compounds	rapamycin
Interactions	Actin, AGING, AKT, AKT1, AKT1S1, AKT2
SciDEX Hypotheses	Selective TFEB Cofactor Enhancement
KG Connections	610 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

TFE3 Gene

gene · 989 words

→

TFE3 Protein

protein · 905 words

→

Pathway Diagram

graph TD
    TFE3["TFE3"] -->|"Interacts With"| Cancer["Cancer"]
    TFE3["TFE3"] -->|"Interacts With"| Als["Als"]
    TFE3["TFE3"] -->|"Interacts With"| Ms["Ms"]
    TFE3["TFE3"] -->|"Interacts With"| Fibrosis["Fibrosis"]
    TFE3["TFE3"] -->|"Therapeutic Target"| Multiple_Sclerosis["Multiple Sclerosis"]
    TFE3["TFE3"] -->|"Therapeutic Target"| Alzheimer["Alzheimer"]
    TFE3["TFE3"] -->|"Therapeutic Target"| Parkinson["Parkinson"]
    TFE3["TFE3"] -->|"Activates"| Hepatitis["Hepatitis"]
    AMBRA1["AMBRA1"] -->|"Inhibits"| TFE3["TFE3"]
    OPTN["OPTN"] -->|"Interacts With"| TFE3["TFE3"]
    CASP3["CASP3"] -->|"Interacts With"| TFE3["TFE3"]
    AKT1["AKT1"] -->|"Interacts With"| TFE3["TFE3"]
    CALCOCO2["CALCOCO2"] -->|"Interacts With"| TFE3["TFE3"]
    style TFE3 fill:#8d4900,color:#e0e0e0
    style Cancer fill:#b71c1c,color:#e0e0e0
    style Als fill:#b71c1c,color:#e0e0e0
    style Ms fill:#b71c1c,color:#e0e0e0
    style Fibrosis fill:#b71c1c,color:#e0e0e0
    style Multiple_Sclerosis fill:#b71c1c,color:#e0e0e0
    style Alzheimer fill:#b71c1c,color:#e0e0e0
    style Parkinson fill:#b71c1c,color:#e0e0e0
    style Hepatitis fill:#b71c1c,color:#e0e0e0
    style AMBRA1 fill:#0d47a1,color:#e0e0e0
    style OPTN fill:#8d4900,color:#e0e0e0
    style CASP3 fill:#8d4900,color:#e0e0e0
    style AKT1 fill:#8d4900,color:#e0e0e0
    style CALCOCO2 fill:#8d4900,color:#e0e0e0

Outgoing (310)

Target	Relation	Type	Str
renal tumorigenesis	promotes	process	0.92
mitophagy	promotes	process	0.90
reticulophagy	activates	process	0.90
HSPA1A	regulates	gene	0.80
Kidney Cancer	causes	disease	0.80
Als	activates	disease	0.75
Als	regulates	disease	0.75
AUTOPHAGY	activates	gene	0.70
oxidative stress response	participates_in	pathway	0.70
TFEB loss	modulates	process	0.70
TFEB	inhibits	gene	0.70
autophagy pathway	participates_in	pathway	0.70
MTOR	activates	gene	0.70
Mtor	activates	pathway	0.70
Autophagy	activates	pathway	0.70
Alzheimer	associated_with	disease	0.65
Insulin Resistance	activates	disease	0.65
Fatty Liver	activates	disease	0.65
Aging	activates	disease	0.65
Parkinson	activates	disease	0.65
Multiple Sclerosis	associated_with	disease	0.65
Neuroinflammation	activates	disease	0.65
Obesity	activates	disease	0.65
Alzheimer	activates	disease	0.65
ALS	interacts_with	disease	0.65
Ms	interacts_with	disease	0.65
Als	inhibits	disease	0.65
Neurodegeneration	activates	disease	0.65
Cancer	interacts_with	disease	0.65
Tumor	regulates	disease	0.65
Als	interacts_with	disease	0.65
Diabetes	activates	disease	0.65
Parkinson	associated_with	disease	0.65
Hepatitis	activates	disease	0.65
Nafld	activates	disease	0.65
Cancer	therapeutic_target	disease	0.65
Inflammation	activates	disease	0.65
Fibrosis	interacts_with	disease	0.65
Parkinson	therapeutic_target	disease	0.65
Cirrhosis	therapeutic_target	disease	0.65
Nafld	regulates	disease	0.65
Carcinoma	therapeutic_target	disease	0.65
Atherosclerosis	regulates	disease	0.65
Diabetes	regulates	disease	0.65
Cancer	activates	disease	0.65
Fibrosis	therapeutic_target	disease	0.65
Cancer	regulates	disease	0.65
Neurodegeneration	regulates	disease	0.65
Parkinson	expressed_in	disease	0.65
Tumor	activates	disease	0.65

Incoming (300)

Source	Relation	Type	Str
FLCN	inhibits	protein	0.95
Menin	regulates	protein	0.95
Rag-GTPases	inhibits	protein	0.95
h-6f30a803	targets	hypothesis	0.90
NRF2	regulates	gene	0.90
AMBRA1	inhibits	protein	0.80
STING	upregulates	protein	0.80
TFEB	activates	gene	0.80
ULK1	regulates	gene	0.60
ATG12	interacts_with	gene	0.60
DEPTOR	interacts_with	gene	0.60
FIP200	interacts_with	gene	0.60
MAP3K7	activates	gene	0.60
PP2A	activates	gene	0.60
KEAP1	activates	gene	0.60
SQSTM1	activates	gene	0.60
TAK1	activates	gene	0.60
NRF2	activates	gene	0.60
NFE2L2	activates	gene	0.60
TFEB	associated_with	gene	0.60
NBR1	associated_with	gene	0.60
FOXO1	associated_with	gene	0.60
PPARA	associated_with	gene	0.60
OPTN	associated_with	gene	0.60
PPARG	associated_with	gene	0.60
VPS4A	associated_with	gene	0.60
SREBF1	associated_with	gene	0.60
TSC2	activates	gene	0.60
DDIT3	phosphorylates	entity	0.60
DEPTOR	phosphorylates	entity	0.60
EGF	phosphorylates	entity	0.60
EGFR	phosphorylates	entity	0.60
EIF2A	phosphorylates	entity	0.60
EIF2AK3	phosphorylates	entity	0.60
ERN1	phosphorylates	entity	0.60
AKT	activates	gene	0.60
NBR1	activates	gene	0.60
PI3K	activates	gene	0.60
RB1	activates	gene	0.60
RB1CC1	activates	gene	0.60
AKT	regulates	gene	0.60
CDK6	implicated_in	gene	0.60
IL6	implicated_in	gene	0.60
NRF2	implicated_in	gene	0.60
CDH1	interacts_with	gene	0.60
GENES	interacts_with	gene	0.60
HSPB1	associated_with	gene	0.60
AMPK	activates	gene	0.60
ANTIOXIDANT GENES	interacts_with	gene	0.60
PARKINSON'S DISEASE	activates	gene	0.60

Targeting Hypotheses (4)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
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
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

Mentioning Analyses (2)

Scientific analyses that reference this entity

How do different organelle-specific autophagy pathways coordinate during neurode

neurodegeneration | 2026-04-07 | 7 hypotheses Top: 0.772

Does TFEB dysfunction cause neurodegeneration or represent a compensatory respon

neurodegeneration | 2026-04-03 | 7 hypotheses Top: 0.697

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (6)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Mammalian lipophagy: process and function. [PMID:41681129]	Zhao R, Dai E, Kang R, Liu J, Klionsky D	Autophagy	2026
NRF2 activation by CDDO-Im regulates inflammatory and autophagy pathways in huma [PMID:41274321]	Chu CT, Uruno A, Suzuki T, Taguchi K, Ba	Free radical biology & medicin	2026
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
Plasma membrane-to-lysosome FGR signaling regulates endocytosis-associated lysos [PMID:41493272]	Yin Q, Qian J, Ding X, Ren X, Li S et al	J Cell Biol	2026
AMPK promotes TFEB transcriptional activity through dephosphorylation at both MT [PMID:41661247]	Negoita F, Fraguas Bringas C, Hellberg K	Autophagy	2026
TFE3-Rearranged and TFEB-Altered Renal Cell Carcinomas: Molecular Landscape and [PMID:41899560]	Portu M, Balsa M, Cotaina M, Anguera G,	Cancers (Basel)	2026

Debates (2)

Multi-agent debates referencing this entity

The abstract mentions multiple organelles synchronously present structural deran

closed · Rounds: 4 · Score: 0.80 · 2026-04-21

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 TFE3 in their description or question text

No additional research found