concept

RAF

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about RAF: 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.

1306Connections

19Hypotheses

0Analyses

50Outgoing

50Incoming

17Experiments

0Debates

No summary available yet.

View on Wiki →

No AI portrait yet

💡 Concept Info

Name	RAF
Key Genes/Proteins	AKT, ALZHEIMER, AND, APOPTOSIS, App, AUTOPHAGY
Related Diseases	Aging, Als, ALS, Alzheimer, ALZHEIMER'S
Related Pathways	Akt, Apoptosis, Autophagy

Wiki Pages (10)

Knowledge base pages for this entity

Pathway Diagram

graph TD
    RAF["RAF"]
    style RAF fill:#1a237e,stroke:#4fc3f7,stroke-width:3px
    RAF -->|"activates"| MEK([MEK])
    RAF -->|"target for"| Ms["Ms"]
    RAF -.->|"inhibits"| Cancer["Cancer"]
    RAF -->|"target for"| Aging["Aging"]
    RAF -->|"target for"| Lymphoma["Lymphoma"]
    RAF -->|"target for"| Tumor["Tumor"]
    RAF -->|"target for"| Als["Als"]
    RAF -->|"activates"| RAS([RAS])
    Vemurafenib{"Vemurafenib"} -.->|"inhibits"| RAF
    NST_628{"NST-628"} -->|"binds to"| RAF
    RAS -->|"activates"| RAF
    AKT([AKT]) -->|"activates"| RAF
    CANCER["CANCER"] -->|"activates"| RAF
    ERK([ERK]) -->|"activates"| RAF
    MTOR([MTOR]) -->|"activates"| RAF
    PI3K([PI3K]) -->|"activates"| RAF

Outgoing (318)

Target	Relation	Type	Str
Mapk Pathway	activates	pathway	0.95
MEK	activates	protein	0.95
MEK	phosphorylates	protein	0.90
cancer	associated_with	disease	0.85
oxidative stress response	participates_in	pathway	0.70
Cancer	inhibits	disease	0.65
Lymphoma	inhibits	disease	0.65
Stroke	activates	disease	0.65
Tumor	activates	disease	0.65
Tumor	inhibits	disease	0.65
ALS	regulates	disease	0.65
Parkinson	activates	disease	0.65
Als	therapeutic_target	disease	0.65
Ms	therapeutic_target	disease	0.65
ALS	interacts_with	disease	0.65
Cancer	activates	disease	0.65
Cancer	therapeutic_target	disease	0.65
Senescence	activates	disease	0.65
Aging	activates	disease	0.65
Inflammation	regulates	disease	0.65
Cancer	interacts_with	disease	0.65
Carcinoma	activates	disease	0.65
Aging	therapeutic_target	disease	0.65
Lymphoma	therapeutic_target	disease	0.65
Alzheimer	activates	disease	0.65
Neurodegeneration	regulates	disease	0.65
Aging	inhibits	disease	0.65
Tumor	therapeutic_target	disease	0.65
Fibrosis	inhibits	disease	0.60
Neuroinflammation	therapeutic_target	disease	0.60
Ferroptosis	inhibits	disease	0.60
Multiple Sclerosis	therapeutic_target	disease	0.60
Cancer	regulates	disease	0.60
Frontotemporal Dementia	causes	disease	0.60
Senescence	therapeutic_target	disease	0.60
Neurodegeneration	activates	disease	0.60
Amyotrophic Lateral Sclerosis	regulates	disease	0.60
Amyotrophic Lateral Sclerosis	causes	disease	0.60
Huntington	expressed_in	disease	0.60
Parkinson	expressed_in	disease	0.60
Alzheimer	expressed_in	disease	0.60
Dementia	causes	disease	0.60
Addiction	therapeutic_target	disease	0.60
Aging	expressed_in	disease	0.60
Frontotemporal Dementia	associated_with	disease	0.60
Amyotrophic Lateral Sclerosis	expressed_in	disease	0.60
Multiple Sclerosis	transports	disease	0.60
Depression	activates	disease	0.60
Diabetes	associated_with	disease	0.60
Dementia	associated_with	disease	0.60

Incoming (988)

Source	Relation	Type	Str
Vemurafenib	inhibits	drug	0.90
Dabrafenib	inhibits	drug	0.90
HSP90-CDC37	interacts_with	protein	0.90
NST-628	binds_to	drug	0.88
SHOC2 phosphatase complex	activates	protein	0.85
NATURAL PRODUCTS	regulates	compound	0.80
RAS	activates	protein	0.80
RAS	regulates	protein	0.70
PI3K	activates	gene	0.65
CANCER	inhibits	disease	0.65
ERK	activates	gene	0.65
CANCER	activates	disease	0.65
AKT	activates	gene	0.65
MTOR	activates	gene	0.65
H3F3A	associated_with	gene	0.60
TARDBP	regulates	gene	0.60
LAMP1	regulates	gene	0.60
RNA	regulates	gene	0.60
OVERVIEW	biomarker_for	gene	0.60
BRAF	associated_with	gene	0.60
CIC	associated_with	gene	0.60
EIF4EBP1	regulates	gene	0.60
MAP1LC3B	regulates	gene	0.60
PPARG	regulates	gene	0.60
CPT1A	regulates	gene	0.60
RPS6KB1	regulates	gene	0.60
OVERVIEW	inhibits	gene	0.60
PPARA	regulates	gene	0.60
ATG	regulates	gene	0.60
ARF6	interacts_with	gene	0.60
FTLD	expressed_in	gene	0.60
LRP2	regulates	gene	0.60
ALS	expressed_in	gene	0.60
APOE4	expressed_in	gene	0.60
DNA	regulates	gene	0.60
CTSD	regulates	gene	0.60
ATP	regulates	gene	0.60
NADH	regulates	gene	0.60
MTOR	regulates	gene	0.60
ALZHEIMER	expressed_in	gene	0.60
MTORC1	regulates	gene	0.60
PIK3C3	regulates	gene	0.60
CAT	regulates	gene	0.60
TDP-43	regulates	gene	0.60
MITOCHONDRIA	activates	gene	0.60
RAB7A	regulates	gene	0.60
SREBF1	regulates	gene	0.60
PPARGC1A	regulates	gene	0.60
RUBCN	regulates	gene	0.60
ACTB	regulates	gene	0.60

Targeting Hypotheses (19)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Endosomal trafficking defects are the common upstream lesion	0.730	neurodegeneration	What determines the temporal sequence of
TFAM overexpression creates mitochondrial donor-recipient gr	0.725	neurodegeneration	Mitochondrial transfer between astrocyte
H3: APOE4 Impairs Cholesterol Trafficking, Triggering Astroc	0.720	neurodegeneration	Do APOE4-driven senescent astrocytes cau
H6: Layer II–Specific Loss of NPTX2 and Aberrant AMPAR Traff	0.720	neurodegeneration	Entorhinal cortex layer II vulnerability
Lysosomal Enzyme Trafficking Correction	0.706	neurodegeneration	Autophagy-lysosome pathway convergence a

APOE4 hypolipidation and ABCA1 mistrafficking impair cholest	0.694	molecular biology	Does APOE4's reduced lipid-binding direc
Palmitoylation-Targeted BACE1 Trafficking Disruptors	0.693	neurodegeneration	Lipid raft composition changes in synapt
Compromised Lysosomal Acidification and Trafficking Due to N	0.693	neurodegeneration	What mechanisms underlie neuronal resist
Sphingomyelin Synthase Activators for Raft Remodeling	0.692	neurodegeneration	Lipid raft composition changes in synapt
APOE-Mediated Synaptic Lipid Raft Stabilization	0.649	neurodegeneration	Mechanistic role of APOE in neurodegener
APOE4 preferentially signals through LRP1 over LDLR, alterin	0.610	neuroscience	APOE4-driven lipid metabolism dysregulat
H4: Hyperconnected Hub Status Creates Proteostatic Traffic J	0.600	neurodegeneration	Entorhinal cortex layer II vulnerability
Tau-trafficking GWAS loci define a druggable PTK2B endocytos	0.600	Alzheimer's disease	-
Miro1-Mediated Mitochondrial Trafficking Enhancement Therapy	0.549	neurodegeneration	Mitochondrial transfer between neurons a
Co-translational mRNA localization as a sensor for RNA granu	0.520	neuroscience	How can subcellular compartmentalization
VPS35 Retromer Restoration to Rescue Endosomal Protein Traff	0.517	proteomics	Quantitative proteomics of the aging syn
BIN1-dependent trafficking defects determine whether post-Aβ	0.460	neurodegeneration	Does tau dendritic missorting persist in
Glucosylceramide accumulation nucleates alpha-synuclein aggr	0.000	Parkinson's disease	GBA-Synuclein Loop Therapeutics for PD
TFEB-Mediated Retromer Biogenesis to Restore Endosomal-Lysos	0.000	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (17)

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
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
Chaperone-Mediated Autophagy Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Presymptomatic GRN Carrier Intervention Timing — Biomarker-Guided Ther	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
Proteasome-Ubiquitin System Dysfunction Validation in Parkinson's Dise	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
TMEM106B Haplotype as Genetic Modifier in FTD — Mechanism and Therapeu	validation	Neurodegeneration	0.400	0.50	human	proposed	$2,730,000
ER-Golgi Secretory Pathway Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,500,000
Validation: Membrane-Nucleation in iPSC Neurons	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Oligodendrocyte-Myelin Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,100,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Designed endocytosis-inducing proteins degrade targets and amplify signals. [PMID:39322662]	Huang B, Abedi M, Ahn G, Coventry B, Sap	Nature	2025	1
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
Collapse of late endosomal pH elicits a rapid Rab7 response via the V-ATPase and [PMID:38578235]	Mulligan RJ, Magaj MM, Digilio L, Redema	J Cell Sci	2024	1
IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases. [PMID:37031050]	Alberini CM	Trends Neurosci	2023	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
Machine Learning and Novel Biomarkers for the Diagnosis of Alzheimer's Disease. [PMID:33803217]	Chang CH, Lin CH, Lane HY	Int J Mol Sci	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
Interactions of IGF-II with the IGF2R/cation-independent mannose-6-phosphate rec [PMID:19251056]	Brown J, Jones EY, Forbes BE	Vitam Horm	2009	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
ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and [PMID:41806112]	Mrkacek M, Tumova M, Puskasu A, Utekal P	FASEB journal : official publi	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
Amyloid-β fibrils accumulated in preeclamptic placentas suppress cytotrophoblast [PMID:41558820]	Nishioka K, Ikezaki M, Iwahashi N, Araka	Life Sci Alliance	2026	0
An anti-inflammatory neuroenhancer mitigates amyloid-β pathology to improve Alzh [PMID:41696149]	Fang W, Zhao J, Li L, Wang Y, Xu ZP et a	Mater Today Bio	2026	0
Intranasal administration of neural stem cell-derived extracellular vesicles pre [PMID:41923110]	Natale Francesca; Dellaria Alice; Nifo S	Alzheimer's research & the	2026	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning RAF in their description or question text

APOE4 hypolipidation and ABCA1 mistrafficking impair cholesterol efflux and seco

Score: 0.694 · molecular biology · 2026-04-24

A plausible upstream submechanism is that lipid-poor APOE4 disrupts ABCA1 trafficking, likely via ARF6-associated endoso

Palmitoylation-Targeted BACE1 Trafficking Disruptors

Score: 0.693 · neurodegeneration · 2026-04-02

## Mechanistic Overview Palmitoylation-Targeted BACE1 Trafficking Disruptors starts from the claim that modulating BACE1

Compromised Lysosomal Acidification and Trafficking Due to Neuronal V-ATPase Sub

Score: 0.693 · neurodegeneration · 2026-04-26

Neurons express a distinct V-ATPase subunit isoform profile (ATP6V0C splice variants and ATP6V1G2 enrichment) resulting

Sphingomyelin Synthase Activators for Raft Remodeling

Score: 0.692 · neurodegeneration · 2026-04-02

## Mechanistic Overview Sphingomyelin Synthase Activators for Raft Remodeling starts from the claim that modulating SGMS

APOE-Mediated Synaptic Lipid Raft Stabilization

Score: 0.649 · neurodegeneration · 2026-04-02

## Mechanistic Overview APOE-Mediated Synaptic Lipid Raft Stabilization starts from the claim that modulating SPTLC1 wit

APOE4 preferentially signals through LRP1 over LDLR, altering endosomal choleste

Score: 0.610 · neuroscience · 2026-04-22

**Molecular Mechanism and Rationale** The apolipoprotein E4 (APOE4) isoform, present in approximately 25% of the popula

H4: Hyperconnected Hub Status Creates Proteostatic Traffic Jams

Score: 0.600 · neurodegeneration · 2026-04-22

## Mechanistic Overview H4: Hyperconnected Hub Status Creates Proteostatic Traffic Jams starts from the claim that modul

Miro1-Mediated Mitochondrial Trafficking Enhancement Therapy

Score: 0.549 · neurodegeneration · 2026-04-02

Small molecule activators of Miro1 GTPase activity increase mitochondrial motility and facilitate intercellular transfer

Co-translational mRNA localization as a sensor for RNA granule trafficking defec

Score: 0.520 · neuroscience · 2026-04-26

Local protein synthesis at synaptic compartments requires intact mRNA granule transport via ZBP1 and TDP-43 in granules.

VPS35 Retromer Restoration to Rescue Endosomal Protein Trafficking

Score: 0.517 · proteomics · 2026-04-25

VPS35 Retromer Restoration to Rescue Endosomal Protein Trafficking

BIN1-dependent trafficking defects determine whether post-Aβ tau missorting reso

Score: 0.460 · neurodegeneration · 2026-04-25

Aβ initially perturbs tau localization, but persistence depends on BIN1-regulated membrane and endocytic trafficking tha

Glucosylceramide accumulation nucleates alpha-synuclein aggregation via lipid ra

Score: 0.000 · Parkinson's disease · 2026-04-26

We propose that GBA deficiency-driven accumulation of glucosylceramide (GlcCer) in lysosomal membranes creates ordered l

TFEB-Mediated Retromer Biogenesis to Restore Endosomal-Lysosomal Trafficking in

Score: 0.000 · proteomics · 2026-04-26

This hypothesis proposes that TFEB activation can restore synaptic function in aging by simultaneously upregulating both

RAF

Understanding Entity Pages

Wiki Pages (10)

TRAF2 Gene

TRAF6 Protein

ARAF Gene

c-Raf Protein (RAF1)

BRAF — B-Raf Proto-Oncogene, Serine/Threonine Kinase

RAF1 — RAF1 Proto-Oncogene, Serine/Threonine Kinase (c-Raf)

TRAF3

TRAF2 Protein

TRAF6 Protein

TRAF6 Gene

Pathway Diagram

Outgoing (318)

Incoming (988)

Targeting Hypotheses (19)

Mentioning Analyses (0)

Experiments (17)

Related Papers (20)

Debates (0)

Related Research

APOE4 hypolipidation and ABCA1 mistrafficking impair cholesterol efflux and seco

Palmitoylation-Targeted BACE1 Trafficking Disruptors

Compromised Lysosomal Acidification and Trafficking Due to Neuronal V-ATPase Sub

Sphingomyelin Synthase Activators for Raft Remodeling

APOE-Mediated Synaptic Lipid Raft Stabilization

APOE4 preferentially signals through LRP1 over LDLR, altering endosomal choleste

H4: Hyperconnected Hub Status Creates Proteostatic Traffic Jams

Miro1-Mediated Mitochondrial Trafficking Enhancement Therapy

Co-translational mRNA localization as a sensor for RNA granule trafficking defec

VPS35 Retromer Restoration to Rescue Endosomal Protein Trafficking

BIN1-dependent trafficking defects determine whether post-Aβ tau missorting reso

Glucosylceramide accumulation nucleates alpha-synuclein aggregation via lipid ra

TFEB-Mediated Retromer Biogenesis to Restore Endosomal-Lysosomal Trafficking in