gene

TNF

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TNF: 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.

5625Connections

6Hypotheses

23Analyses

50Outgoing

50Incoming

1Experiments

20Debates

Summary

The TNF gene encodes tumor necrosis factor alpha (TNF-α), a pivotal pro-inflammatory cytokine central to neuroinflammation in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and ALS.

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🧬 Gene Info

Gene Symbol	TNF
Full Name	Tumor Necrosis Factor
Aliases	TNF-α
Chromosome	6p21.33
Function	is an important component in the neurobiology of neurodegenerative diseases.
Primary Expression	immune cells and endothelial cells](/cell-types/endothelial-cells) - Activates NF-κB and MAPK pathways - [Predominantly pro-survival sign
Molecular Weight	26 kDa
Exons	3
Pathways	NF-κB signaling, NF-κB, MAPK, PI3K
Ensembl ID	ENSG00000232890
GeneCards	TNF
Human Protein Atlas	TNF
TNFR1 (p55)	Ubiquitous, death domain
TNFR2 (p75)	Immune cells, tissue-specific
Caspase Activation	Apoptosis pathways
Associated Diseases	A1_astrocytes, AD, Age-related macular degeneration, Aging, Alopecia Areata, Als
Known Drugs/Compounds	ACBA, Adalimumab, Andrographis paniculata, anti-TNF-α monoclonal antibody, BAICALEIN, berberine
Interactions	A2M, ABCA1, ABCB1, ABCG1, ABCG2, ACE
SciDEX Hypotheses	Temporal Window Specificity
KG Connections	5624 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

🧬 3D Structure: TNF — PDB 1TNF Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    subgraph Signaling["Signaling"]
        TNF["TNF"] -->|"activates"| ASTROCYTES["ASTROCYTES"]
        TNF["TNF"] -->|"activates"| Tumor["Tumor"]
        TNF["TNF"] -->|"activates"| Apoptosis["Apoptosis"]
        TNF["TNF"] -->|"activates"| Als_2["Als"]
        TNF["TNF"] -->|"activates"| Immune_Response["Immune Response"]
        TNF["TNF"] -.->|"inhibits"| Nf__b["Nf-Kappab"]
        MICROGLIA_3["MICROGLIA"] -->|"activates"| TNF["TNF"]
        INFLAMMATION["INFLAMMATION"] -->|"activates"| TNF["TNF"]
    end
    subgraph Therapeutic["Therapeutic"]
        TNF["TNF"] -->|"expressed in"| Als["Als"]
        TNF["TNF"] -->|"expressed in"| Inflammation["Inflammation"]
        TNF["TNF"] -->|"expressed in"| Tumor_1["Tumor"]
    end
    subgraph Pathology["Pathology"]
        AKT["AKT"] -->|"associated with"| TNF["TNF"]
        MICROGLIA["MICROGLIA"] -->|"associated with"| TNF["TNF"]
        APP["APP"] -->|"associated with"| TNF["TNF"]
        CASP3["CASP3"] -->|"associated with"| TNF["TNF"]
    end
    style TNF fill:#4a1a6b,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
    style ASTROCYTES fill:#006494,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Tumor fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Apoptosis fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Als fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Inflammation fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Tumor_1 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Als_2 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Immune_Response fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Nf__b fill:#1b5e20,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style AKT fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style MICROGLIA fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style APP fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style CASP3 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style MICROGLIA_3 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style INFLAMMATION fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0

Outgoing (2962)

Target	Relation	Type	Str
CYTOKINES	inhibits	gene	1.00
Tumor	associated_with	disease	1.00
IL-6	regulates	gene	1.00
CYTOKINES	activates	gene	1.00
STROKE	associated_with	disease	1.00
Ferroptosis	activates	pathway	1.00
TNF-Α	inhibits	gene	1.00
CANCER	therapeutic_target	gene	1.00
INFLAMMATION	inhibits	gene	1.00
NF-ΚB	inhibits	gene	1.00
CORTEX	associated_with	brain_region	1.00
Autophagy	inhibits	pathway	1.00
Inflammasome	activates	pathway	1.00
Oxidative Stress	therapeutic_target	pathway	1.00
Tgf-Β	activates	pathway	1.00
Inflammation	inhibits	disease	1.00
Stroke	activates	disease	1.00
AKT	inhibits	gene	1.00
Mapk	therapeutic_target	pathway	1.00
BCL-2	activates	gene	1.00
Autophagy	activates	pathway	1.00
INFLAMMATION	regulates	gene	1.00
Infection	activates	disease	1.00
Als	expressed_in	disease	1.00
PI3K	inhibits	gene	1.00
Tumor	regulates	disease	1.00
AKT1	therapeutic_target	gene	1.00
MTOR	activates	gene	1.00
Toll-Like Receptor	inhibits	pathway	1.00
Als	regulates	disease	1.00
Depression	activates	disease	1.00
Inflammation	therapeutic_target	disease	1.00
NLRP3	associated_with	gene	1.00
ASTROCYTES	activates	cell_type	1.00
Inflammation	expressed_in	disease	1.00
neuroinflammation	activates	process	1.00
BDNF	activates	gene	1.00
PI3K	activates	gene	1.00
Apoptosis	inhibits	pathway	1.00
Inflammation	activates	disease	1.00
Mapk	activates	pathway	1.00
STAT3	activates	gene	1.00
Cancer	activates	disease	1.00
Nf-Κb	activates	pathway	1.00
Nf-Kb	activates	pathway	1.00
Aging	activates	disease	1.00
Inflammation	regulates	disease	1.00
IL-6	inhibits	gene	1.00
AKT	activates	gene	1.00
INFLAMMATION	associated_with	gene	1.00

Incoming (2663)

Source	Relation	Type	Str
NLRP3	inhibits	gene	1.00
AKT	associated_with	gene	1.00
APP	associated_with	gene	1.00
IL-6	inhibits	gene	1.00
TNF-Α	activates	gene	1.00
MICROGLIA	associated_with	gene	1.00
IL-6	associated_with	gene	1.00
CASP3	associated_with	gene	1.00
APOPTOSIS	associated_with	gene	1.00
NEURODEGENERATION	activates	gene	1.00
AMYLOID	associated_with	protein	1.00
APOPTOSIS	targets	gene	1.00
IL-1B	associated_with	gene	1.00
NF-KB	associated_with	protein	1.00
ROS	activates	gene	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
BAX	activates	gene	1.00
NEURODEGENERATION	associated_with	gene	1.00
MICROGLIA	activates	gene	1.00
IL-6	activates	gene	1.00
INFLAMMATION	activates	gene	1.00
PARKINSON'S DISEASE	associated_with	disease	1.00
IL-6	expressed_in	gene	1.00
AUTOPHAGY	inhibits	gene	1.00
TNF-Α	associated_with	gene	1.00
ROS	inhibits	gene	1.00
PINK1	activates	gene	1.00
APOPTOSIS	activates	gene	0.98
TAU	associated_with	gene	0.98
SOD1	associated_with	gene	0.98
infliximab	inhibits	drug	0.98
Adalimumab	inhibits	drug	0.95
L5 Nerve Compression	upregulates	process	0.95
Qingqi Liangying Formula	downregulates	drug	0.95
anti-TNF-α monoclonal antibody	inhibits	drug	0.95
ENDOTHELIAL CELLS	activates	cell_type	0.95
IPA	downregulates	compound	0.95
Berberine	inhibits	compound	0.95
Safranal	downregulates	compound	0.95
Spike Protein 1	upregulates	protein	0.95
Lapiferin	downregulates	compound	0.92
AMS-17	downregulates	drug	0.90
Gallic Acid	downregulates	compound	0.90
Betulinic Acid	downregulates	compound	0.90
XPro1595	inhibits	drug	0.90
Hearing Loss	upregulates	phenotype	0.90
Urolithin A	inhibits	drug	0.90
Dihydrotestosterone	inhibits	compound	0.90
Infliximab	inhibits	drug	0.90
Paeoniflorin	downregulates	compound	0.90

Targeting Hypotheses (6)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
TNF-α/IL-1β-Cx43 Hemichannel Axis as Upstream Link Between S	0.663	cell-biology	What is the relative contribution of con
TNF-α/NF-κB Axis Upregulates P2RY12 in VSMCs	0.650	neurodegeneration	What determines P2RY12 receptor expressi
TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement	0.600	neuroinflammation	How does sevoflurane-induced NF-κB activ
TNFRSF25-Mediated Aging Exosome Pathway Inhibition	0.587	neurodegeneration	Gene expression changes in aging mouse b
Temporal Window Specificity	0.455	clinical-neurology	Why do systemic anti-inflammatory drugs

Combinatorial Il-1α/TNFα/C1q Antagonism with Selective Agoni	0.000	-	Astrocyte Reactivity Subtypes in Neurode

Mentioning Analyses (23)

Scientific analyses that reference this entity

Experiments (1)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Network pharmacology analysis of QTJD active compounds and pathways	exploratory	Mycoplasma pneumoniae pneumoni	0.900	0.00	computational network analysis	proposed	N/A

Related Papers (4)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Death receptor 3: A paradoxical biomarker and therapeutic target in pan-cancer. [PMID:41605339]	Fang W, Du J, Xu Z, Liu Q, Liu Y et al.	Crit Rev Oncol Hematol	2026
Homocysteine as a biomarker in arthritis and depression: Evidence from NHANES an [PMID:41693749]	Deng C, He Z, Zhu X	SAGE Open Med	2026
The involvement of TNFRSF25 in age-related hearing loss. [PMID:41882185]	Roche MV, Tang PC, Yan D, De Marchena MR	Hum Genet	2026
Maternal immune activation perturbs intestinal niche through microbial glyceroph [PMID:41926285]	Chang H, Zhu X, Shen C, Xu X, Ni Y et al	Cell Rep	2026

Debates (20)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning TNF in their description or question text

Combinatorial Il-1α/TNFα/C1q Antagonism with Selective Agonism

Score: 0.000 · unknown disease · 2026-04-28

Simultaneously blocking the classical A1-inducing triad while specifically activating alternative pathways through Nrf2

TNF

Understanding Entity Pages

Summary

Wiki Pages (21)

TNF - Tumor Necrosis Factor

Tumor Necrosis Factor Alpha (TNF-α) as a Neurodegenerative Disease Biomarker

TNF Signaling Pathway in Neurodegeneration

TRAIL Gene (TNFSF10)

TNFAIP3 — TNF Alpha Induced Protein 3 (A20)

TNFSF12 Gene (TWEAK)

TNF Gene

TNFRSF1A Gene

TACI Gene (TNFRSF13B)

TNFAIP6 — TNF Alpha Induced Protein 6 (TSG-6)

TNFAIP1 — TNF Alpha Induced Protein 1

BAFFR Gene (TNFRSF13C)

TNFAIP8L1 — TNF Alpha Induced Protein 8 Like 1

TNFAIP8 — TNF Alpha Induced Protein 8 (SCC-S2)

TNFRSF1B Gene

Tumor Necrosis Factor (TNF)

TNFRSF21 Gene

TRAIL (TNF-Related Apoptosis-Inducing Ligand) Protein

TNF Alpha Protein

TNFRSF1B Gene

TNFR2 (TNFRSF1B Protein)

Pathway Diagram

Outgoing (2962)

Incoming (2663)

Targeting Hypotheses (6)

Mentioning Analyses (23)

Blood-brain barrier tight junction disruption by neuroinflammatory cytokines

Why does PRKN-mediated mitophagy, typically protective, cause harmful mitochondr

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

Why do systemic anti-inflammatory drugs fail in AD despite cardiovascular effica

Systemic immune profiling and peripheral immune contributions to neurodegenerati

Neuroinflammation and microglial priming in early Alzheimer's Disease

Neuroinflammation and microglial priming in early Alzheimer's Disease

Tau propagation mechanisms and therapeutic interception points

Which cell types show the most significant expression changes for neurodegenerat

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

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

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Epigenetic clocks and biological aging in neurodegeneration

Neuroinflammation resolution mechanisms and pro-resolving mediators

Digital biomarkers and AI-driven early detection of neurodegeneration

Senolytic therapy for age-related neurodegeneration

Microglia-astrocyte crosstalk amplification loops in neurodegeneration

APOE4 structural biology and therapeutic targeting strategies

Astrocyte reactivity subtypes in neurodegeneration

4R-tau strain-specific spreading patterns in PSP vs CBD

Astrocyte Reactivity Subtypes in Neurodegeneration

Digital biomarkers and AI-driven early detection of neurodegeneration

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

Experiments (1)

Related Papers (4)

Debates (20)

Second debate: Microglial TREM2-SYK Pathway Enhancement

Debate: LPCAT3-Mediated Lands Cycle Remodeling as the Primary Ferroptotic Primin

Debate: ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes via PUFA-PE P

Debate: LPCAT3-Mediated Lands Cycle Amplification of Ferroptotic Vulnerability i

Debate: ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes

Should '40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Sele

Should 'ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matt

Hypothesis debate: SASP-Mediated Complement Cascade Amplification

Should PEA-PPARA endocannabinoid signaling be prioritized as a therapeutic strat

Blood-brain barrier tight junction disruption by neuroinflammatory cytokines

Related Research

Combinatorial Il-1α/TNFα/C1q Antagonism with Selective Agonism