gene

TFAM

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TFAM: 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.

815Connections

2Hypotheses

2Analyses

50Outgoing

50Incoming

10Experiments

2Debates

Summary

TFAM is a gene implicated in neurodegeneration research. Key relationships include: activates, inhibits, regulates. Associated with ALS, Aging, Als. Connected to 395 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	TFAM
Chromosome	10q21.1
Protein Type	Transcription Factor
Target Class	Transcription Factor
Function	Drugs targeting TFAM would enhance or modulate its transcriptional activity to increase mitochondrial DNA replication and gene expression, thereby boosting mitochondrial biogenesis and ATP producti...
Mechanism of Action	Drugs targeting TFAM would enhance or modulate its transcriptional activity to increase mitochondrial DNA replication and gene expression, thereby boosting mitochondrial biogenesis and ATP production. Alternatively, indirect approaches activate upstream regulators like PGC-1α and SIRT1 to increase TFAM expression and activity.
Druggability	Medium (0.50)
Clinical Stage	Approved
Molecular Weight	26 kDa
Amino Acids	246 aa
Exons	9
Pathways	Apoptosis, Ferroptosis, Metastasis, Mitochondrial Function, Mitophagy
UniProt ID	Q6LES8
GeneCards	TFAM
Human Protein Atlas	TFAM
Associated Diseases	aging, ALS, Alzheimer, Carcinoma
Known Drugs/Compounds	Cytoplasmic Mitochondrial Dna, Cytoplasmic Mitochondrial DNA, Mitochondrial Dna, Mitochondrial DNA, rapamycin, RAPAMYCIN
Interactions	A2M, ACLY, Actin, AGING, ALOX, ALZHEIMER
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	TFAM overexpression creates mitochondrial donor-re Hippocampal mitochondrial dysfunction accelerates
KG Connections	815 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

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

📄 Experimental Structure

3TMM — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q6LES8 — AlphaFold

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

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

TFAM Gene

gene · 3249 words

→

TFAM Protein

protein · 640 words

→

Pathway Diagram

flowchart TD
    TFAM["TFAM
(Transcription Factor A,
Mitochondrial)"]
    
    MitoBio["Mitochondrial
Biogenesis"]
    MitoFunc["Mitochondrial
Function"]
    MitoDys["Mitochondrial
Dysfunction"]
    
    Neuroinflam["Neuroinflammation"]
    Inflammation["Systemic
Inflammation"]
    
    ALS["Amyotrophic Lateral
Sclerosis (ALS)"]
    PD["Parkinson's
Disease"]
    MS["Multiple
Sclerosis"]
    Neurodegeneration["Neurodegeneration"]
    
    Aging["Cellular
Aging"]
    Ischemia["Cerebral
Ischemia"]
    
    OxStress["Oxidative
Stress"]
    EnergyDeficit["ATP/Energy
Deficit"]
    
    TherapyTarget["Therapeutic
Target"]
    
    TFAM -->|"activates"| MitoBio
    TFAM -->|"enhances"| MitoFunc
    MitoFunc -->|"dysfunction leads to"| MitoDys
    
    MitoDys -->|"causes"| OxStress
    MitoDys -->|"results in"| EnergyDeficit
    
    TFAM -->|"regulates"| Neuroinflam
    TFAM -->|"regulates"| Inflammation
    
    OxStress -->|"promotes"| Neuroinflam
    EnergyDeficit -->|"contributes to"| Neurodegeneration
    
    TFAM -->|"protective against"| ALS
    TFAM -->|"therapeutic target"| PD
    TFAM -->|"inhibits"| MS
    TFAM -->|"associated with"| Neurodegeneration
    
    Neuroinflam -->|"drives"| ALS
    Neuroinflam -->|"contributes to"| PD
    
    TFAM -->|"inhibits"| Ischemia
    TFAM -->|"associated with"| Aging
    
    TFAM -->|"represents"| TherapyTarget
    
    style TFAM fill:#006494
    style MitoBio fill:#1b5e20
    style MitoFunc fill:#1b5e20
    style TherapyTarget fill:#1b5e20
    style MitoDys fill:#ef5350
    style Neuroinflam fill:#ef5350
    style Inflammation fill:#ef5350
    style OxStress fill:#ef5350
    style EnergyDeficit fill:#ef5350
    style ALS fill:#5d4400
    style PD fill:#5d4400
    style MS fill:#5d4400
    style Neurodegeneration fill:#5d4400
    style Aging fill:#5d4400
    style Ischemia fill:#5d4400

Outgoing (437)

Target	Relation	Type	Str
Oxidative Stress	activates	pathway	1.00
Autophagy	associated_with	process	0.95
Inflammation	activates	disease	0.95
Cytoplasmic Mitochondrial DNA	binds	compound	0.95
Cytoplasmic Mitochondrial Dna	binds	compound	0.95
mtDNA Maintenance	mediates	process	0.95
Mitochondrial Biogenesis	promotes	process	0.95
Mitochondrial Dna	binds	compound	0.95
Mitochondrial Dna	involved_in	process	0.95
Mtdna Maintenance	mediates	process	0.93
Acute Kidney Injury	protects_against	disease	0.92
mitochondrial biogenesis	promotes	process	0.92
mitochondrial dysfunction	protects_against	phenotype	0.91
Mitochondrial DNA Synthesis	mediates	process	0.90
Mitochondrial Networks	promotes	pathway	0.90
Mitochondrial Biogenesis	regulates	process	0.90
mitochondrial biogenesis	regulates	process	0.90
Cytoplasmic Mitochondrial Dna	mediates	compound	0.90
autophagy	modulates	process	0.90
neural stem cells	activates	cell_type	0.90
cytoplasmic mitochondrial DNA	associated_with	compound	0.90
mtDNA	regulates	biomarker	0.90
mtDNA	binds_to	molecule	0.90
Inflammation	inhibits	process	0.90
Mitochondrial Dysfunction	causes	disease	0.90
ATP	activates	gene	0.90
inflammation	suppresses	process	0.88
Cytoplasmic Mitochondrial DNA	mediates	compound	0.88
Mitophagy	involved_in	process	0.85
mitochondrial function	regulates	process	0.85
Als	activates	disease	0.85
inflammatory signaling	prevents	pathway	0.85
Mitochondrial Respiration	regulates	process	0.85
Cytokine Release	regulates	process	0.83
innate immune response	suppresses	process	0.80
neural stem cells	regulates	cell_type	0.80
oxidative stress response	participates_in	pathway	0.80
Mitochondrial DNA	modulates	compound	0.80
TNF	inhibits	entity	0.80
Mitochondrial DNA	regulates	biomarker	0.80
Acetylation	modulates	mechanism	0.80
mitochondrial DNA	binds	biological_process	0.80
Apoptosis	activates	pathway	0.80
TFAM_protein	encodes	protein	0.80
OXIDATIVE STRESS	activates	gene	0.80
Mitochondrial Function	activates	pathway	0.80
Mitophagy	activates	pathway	0.80
PINK1	activates	gene	0.80
MITOCHONDRIAL DYSFUNCTION	activates	gene	0.80
NAD+ metabolism	participates_in	pathway	0.75

Incoming (378)

Source	Relation	Type	Str
Mtros	suppresses	compound	0.92
mtROS	downregulates	process	0.90
h-7c3c0f40	targets	hypothesis	0.90
h-4c3210de	targets_gene	hypothesis	0.90
h-28d5b559	targets_gene	hypothesis	0.90
h-98b431ba	targets	hypothesis	0.90
LON	degrades	enzyme	0.88
m6A deficiency	downregulates	process	0.85
PM10	downregulates	compound	0.80
SIRT3	associated_with	gene	0.80
OXIDATIVE STRESS	activates	gene	0.80
acetylation	inhibits	process	0.75
NRF2	activates	protein	0.74
MFN2	activates	gene	0.70
ROS	regulates	gene	0.70
MFN1	activates	gene	0.70
MITOCHONDRIAL DNA	activates	gene	0.70
INFLAMMATION	activates	gene	0.70
APOPTOSIS	activates	gene	0.70
MITOCHONDRIAL DYSFUNCTION	activates	gene	0.70
PINK1	protects_against	gene	0.70
DNM1L	activates	gene	0.70
miR-206-3p	upregulates	drug	0.70
DNA	associated_with	gene	0.70
SIRT3	activates	gene	0.70
NRF1	regulates	gene	0.70
APP	biomarker_for	gene	0.65
NRF1	activates	protein	0.64
AMPK	activates	gene	0.60
P62	expressed_in	gene	0.60
FOXO	activates	gene	0.60
PARKIN	activates	gene	0.60
DNA	causes	gene	0.60
ROS	protects_against	gene	0.60
COX2	inhibits	gene	0.60
ATP	protects_against	gene	0.60
BMAL1	associated_with	gene	0.60
ATP	inhibits	gene	0.60
DNA	regulates	gene	0.60
STING1	associated_with	gene	0.60
ROS	expressed_in	gene	0.60
MICROGLIA	activates	gene	0.60
CGAS	associated_with	gene	0.60
ATF4	activates	gene	0.60
NCOA4	associated_with	gene	0.60
MAP1LC3B	associated_with	gene	0.60
NEURODEGENERATIVE DISORDERS	activates	gene	0.60
LC3	associated_with	gene	0.60
GPX4	associated_with	gene	0.60
ARNTL	associated_with	gene	0.60

Targeting Hypotheses (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TFAM overexpression creates mitochondrial donor-recipient gr	0.725	neurodegeneration	Mitochondrial transfer between astrocyte
Hippocampal mitochondrial dysfunction accelerates with age a	0.374	Alzheimer's disease	Allen Mouse Brain Aging Atlas: cross-age

Mentioning Analyses (2)

Scientific analyses that reference this entity

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

neurodegeneration | 2026-04-03 | 18 hypotheses Top: 0.847

Mitochondrial transfer between astrocytes and neurons

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.813

Experiments (10)

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
TFAM knockdown functional analysis	exploratory	acute kidney injury	0.850	0.00	HK2 cells	proposed	N/A
TFAM and mtDNA analysis in AKI patients	clinical	acute kidney injury	0.800	0.00	human patients	proposed	N/A
Proposed experiment from debate on Mitochondrial transfer between astr	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
s:** - Test MCU overexpression specifically in layer II neurons in hea	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$200,000
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
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
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
Structural Analysis of Human LonP1 Protease Bound with the Native Substrate. [PMID:41900996]	Li M, Liu H, Zhang S, Gao Q, Li S, Wang	Life (Basel, Switzerland)	2026	0
Effect of (-)-Epicatechin on Mitochondrial Homeostasis in Skeletal Muscle of Fem [PMID:41900149]	Herrera-Cogco EC, Herrera-Meza S, Martín	Molecules (Basel, Switzerland)	2026	0
Enhancing the Optical Properties of MAPbI3 Perovskites Passivated with Coordinat [PMID:41908442]	Gamarde M, Jouaiti A, Chartrand D, Antho	ACS omega	2026	0
Butyrate extends health and lifespan in mice with mitochondrial deficiency. [PMID:41648569]	["Gaband\u00e9-Rodr\u00edguez E", "G\u00	bioRxiv : the preprint server	2026	0
PM [PMID:41897431]	["Somayajulu M", "Wright R", "Muhammed F	Antioxidants (Basel, Switzerla	2026	0
m6A deficiency induces dopaminergic neurodegeneration and progressive parkinsoni [PMID:41842966]	["Liu S", "Ren Q", "Mo G", "Li Z", "Huan	The Journal of clinical invest	2026	0
In vitro investigation of miR-206-3p-loaded extracellular vesicles as modulators [PMID:41592400]	["G\u00f6n\u00fcll\u00fc S", "Ayd\u0131n	Biochemical and biophysical re	2026	0
Next-Generation Metabolic Reprogramming in iPSC-Derived Cardiomyocytes: CRISPR-E [PMID:41897402]	["Shahannaz D", "Sugiura T"]	Biomolecules	2026	0
MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial [PMID:41922875]	Burr SP, Auckland K, Glynos A, Dhawanjew	Nature structural & molecular	2026	0

Debates (2)

Multi-agent debates referencing this entity

Mitochondrial transfer between astrocytes and neurons

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

What cell types are most vulnerable in Alzheimers Disease based on SEA-AD transc

closed · Rounds: 4 · Score: 0.90 · 2026-04-03

Related Research

Hypotheses and analyses mentioning TFAM in their description or question text

No additional research found