gene

SYK

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about SYK: 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.

379Connections

7Hypotheses

12Analyses

50Outgoing

50Incoming

0Experiments

20Debates

Summary

A gene referenced in 1 knowledge graph relationship. Key connections: encodes SYK_kinase (protein).

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🧬 Gene Info

Gene Symbol	SYK
Chromosome	9q22
Protein Family	Src family tyrosine kinases
Protein Type	Receptor
Function	is an important component in the neurobiology of neurodegenerative diseases.
Primary Expression	brain microglia (Iba1+ cells) - Increased expression in disease states - Localizes to amyloid plaques in AD
Molecular Weight	72 kDa
Amino Acids	629 aa
Exons	18
Pathways	PI3K, MAPK
UniProt ID	P43405
NCBI Gene ID	6715
GeneCards	SYK
Human Protein Atlas	SYK
Associated Diseases	ALS, Alzheimer, CYTOKINES, PYROPTOSIS
Known Drugs/Compounds	Entospletinib, metformin, Pustulan, R406
Interactions	AIM2, AKT, ALZHEIMER, ALZHEIMER'S DISEASE, AMYLOID, AND
SciDEX Hypotheses	Selective SYK Inhibition for Neuroprotective Micro
KG Connections	375 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: SYK — AlphaFold P43405 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (6)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    SYK["SYK"]
    Alzheimer{"Alzheimer"}
    SYK -->|"activates"| Alzheimer
    Ms{"Ms"}
    SYK -->|"activates"| Ms
    SYK -->|"associated with"| Alzheimer
    TFEB["TFEB"]
    SYK -->|"associated with"| TFEB
    TREM2["TREM2"]
    SYK -->|"associated with"| TREM2
    Als{"Als"}
    SYK -->|"interacts with"| Als
    Obesity{"Obesity"}
    SYK -->|"activates"| Obesity
    Depression{"Depression"}
    SYK -->|"expressed in"| Depression
    SYK -->|"activates"| TREM2
    Apoptosis(["Apoptosis"])
    SYK -->|"activates"| Apoptosis
    Amyloid(["Amyloid"])
    SYK -->|"associated with"| Amyloid
    SYK -->|"associated with"| Apoptosis
    AKT["AKT"]
    AKT -->|"associated with"| SYK
    PI3K["PI3K"]
    PI3K -->|"associated with"| SYK
    APOE["APOE"]
    APOE -->|"associated with"| SYK
    MICROGLIA["MICROGLIA"]
    MICROGLIA -->|"activates"| SYK
    TREM2 -->|"expressed in"| SYK
    IL6["IL6"]
    IL6 -->|"expressed in"| SYK
    IL1B["IL1B"]
    IL1B -->|"expressed in"| SYK
    IL10["IL10"]
    IL10 -->|"expressed in"| SYK
    TAU["TAU"]
    TAU -->|"expressed in"| SYK
    APOPTOSIS["APOPTOSIS"]
    APOPTOSIS -->|"activates"| SYK
    AMYLOID["AMYLOID"]
    AMYLOID -->|"activates"| SYK
    ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"]
    ALZHEIMER_S_DISEASE -->|"activates"| SYK
    style SYK fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (222)

Target	Relation	Type	Str
HIF-1α/c-Myc	regulates	pathway	0.95
Tau Phosphorylation	regulates	process	0.95
Functional Recovery After Spinal Cord Injury	promotes	phenotype	0.95
Macrophage Phagocytosis	regulates	process	0.95
Monocyte-Derived Macrophages	expressed_in	cell_type	0.95
PI3K/AKT/mTOR	regulates	pathway	0.95
macrophage phagocytosis	regulates	process	0.95
Spinal Cord Injury	therapeutic_target	disease	0.93
TREM2-TYROBP signaling	regulates	pathway	0.90
MAPK/ERK pathway	activates	pathway	0.90
Microglia	associated_with	cell_type	0.90
neuroprotective microglial responses	coordinates	mechanism	0.90
Tau Oligomerization	regulates	process	0.90
PI3K/AKT pathway	activates	pathway	0.90
PLCγ2	activates	protein	0.90
acute motor axonal neuropathy	therapeutic_target	disease	0.90
PI3K/Akt/mTOR pathway	activates	pathway	0.90
AMPK/STAT3	regulates	pathway	0.90
axonal regeneration	promotes	process	0.90
TREM2 downstream signaling	regulates	pathway	0.90
mitophagy	modulates	process	0.90
lipid metabolism	modulates	pathway	0.90
locomotor recovery	promotes	phenotype	0.89
lipid droplet accumulation	regulates	phenotype	0.87
CSF1R	cooperates_with	gene	0.85
PLCG2	phosphorylates	gene	0.85
Axonal Regrowth	promotes	process	0.85
CD22 Blockade	mediates	drug	0.80
Aβ Clearance	associated_with	process	0.80
Alzheimer's Disease	involved_in	disease	0.80
oxidative stress response	participates_in	pathway	0.75
Inflammation	therapeutic_target	disease	0.75
Amyloid-Beta Clearance	associated_with	process	0.75
phagocytosis	activates	process	0.70
macrophage inflammatory response	regulates	phenotype	0.70
TREM2 signaling	mediates	pathway	0.70
PI3K/AKT signaling	activates	pathway	0.70
microglia	modulates	cell_type	0.70
Microglial Protective Pathways	regulates	pathway	0.70
MICROGLIA	protects_against	cell_type	0.70
PI3K/AKT/MTOR	causes	pathway	0.70
Trem2 Signaling	activates	pathway	0.70
PI3K complex recruitment	regulates	mechanism	0.70
autophagic tau degradation	inhibits	mechanism	0.70
PLCG2	activates	protein	0.70
neurodegeneration	targets	disease	0.70
PI3K/AKT PATHWAY	causes	pathway	0.70
pyroptosis	participates_in	pathway	0.70
Neuroinflammation	regulates	disease	0.65
Als	regulates	disease	0.65

Incoming (157)

Source	Relation	Type	Str
Entospletinib	inhibits	drug	0.95
TREM2	interacts_with	gene	0.92
Pustulan	activates	compound	0.90
h-d2937ed0	targets	hypothesis	0.90
h-trem2-f3effd21	targets_gene	hypothesis	0.90
TYROBP	activates	gene	0.90
TREM2	upstream_of	gene	0.88
R406	inhibits	drug	0.85
CD22 Blockade	phosphorylates	drug	0.85
TYROBP	recruits_and_activates	gene	0.85
CLEC7A	activates	gene	0.80
INFLAMMATION	therapeutic_target	gene	0.70
APOE	phosphorylates	gene	0.70
TYROBP	phosphorylates	gene	0.70
TYROBP	interacts_with	gene	0.70
TYROBP/DAP12	activates	protein	0.70
APOE	interacts_with	gene	0.70
VCP	regulates	gene	0.65
NLRP3 INFLAMMASOME	degrades	pathway	0.65
CSF	interacts_with	phenotype	0.65
CSF	activates	phenotype	0.65
MICROGLIA	associated_with	cell_type	0.65
ISCHEMIA	regulates	disease	0.65
PYROPTOSIS	regulates	phenotype	0.65
NLRP3 INFLAMMASOME	regulates	pathway	0.65
TYROBP	regulates	gene	0.65
PI3K	associated_with	gene	0.65
APOE	associated_with	gene	0.65
FERROPTOSIS	inhibits	phenotype	0.65
AKT	associated_with	gene	0.65
TREM2	inhibits	gene	0.65
TREM2	mediates	gene	0.65
MACROPHAGE	activates	cell_type	0.65
MICROGLIA	causes	cell_type	0.65
NLRP3	mediates	gene	0.65
DAM	activates	cell_type	0.65
VCP	phosphorylates	gene	0.65
DAM	interacts_with	cell_type	0.65
IL-10	inhibits	gene	0.60
NEUROINFLAMMATION	inhibits	gene	0.60
PHAGOCYTOSIS	inhibits	gene	0.60
BRAIN INJURY	inhibits	gene	0.60
INFLAMMATION	activates	gene	0.60
IL-18	activates	gene	0.60
IL-1	activates	gene	0.60
AMPK	associated_with	gene	0.60
NEURODEGENERATION	associated_with	gene	0.60
NEUROINFLAMMATION	associated_with	gene	0.60
STROKE	associated_with	gene	0.60
APOE	regulates	gene	0.60

Targeting Hypotheses (7)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Microglial TREM2-SYK Pathway Enhancement	0.798	neurodegeneration	Cell type vulnerability in Alzheimers Di
TREM2-SYK microglial activation as a stage-specific Alzheime	0.610	neurodegeneration	Test
αvβ3 Integrin-FAK-SYK-CARD9/NF-κB Pathway	0.580	neuroinflammation	What molecular mechanisms mediate SPP1-i
SYK-Independent TREM2 Pathways Remain Functional in TYROBP D	0.548	neuroinflammation	Why is TYROBP deficiency neuroprotective
TYROBP-SYK Pathway Enhancement	0.480	neurodegeneration	TREM2 Therapeutic Strategy Post-INVOKE-2

TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocy	0.453	neuroinflammation	What molecular mechanisms enable microgl
Selective SYK Inhibition for Neuroprotective Microglia	0.000	-	Cell type vulnerability in Alzheimer's D

Mentioning Analyses (12)

Scientific analyses that reference this entity

TREM2 in Alzheimer's Disease: Mechanisms, Therapeutics, and Biomarkers

neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.861

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

neurodegeneration | 2026-04-17 | 0 hypotheses

Why is TYROBP deficiency neuroprotective when TYROBP is an adapter for multiple

neuroinflammation | 2026-04-14 | 2 hypotheses Top: 0.586

Can biased TREM2 agonists selectively activate DAP12-SYK-PI3K without triggering

molecular biology | 2026-04-12 | 0 hypotheses

Can TREM2 receptor switching from agonism to antagonism be achieved safely witho

neurodegeneration | 2026-04-11 | 0 hypotheses

Experiments (0)

Experimental studies targeting or related to this entity

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

Related Papers (8)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	1
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0
Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurod [PMID:33603230]	Dong Y, D'Mello C, Pinsky W, Lozinski BM	Nature neuroscience	2021	0
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020	0
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2- [PMID:31932797]	Zhou Y, Song WM, Andhey PS, Swain A, Lev	Nat Med	2020	0
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020	0
Multiple Sclerosis Pathology. [PMID:29358320]	Lassmann H	Cold Spring Harbor perspective	2018	0

Debates (20)

Multi-agent debates referencing this entity

Extended debate: TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegenera

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Debate: TREM2 Microglial Activation Rescues Amyloid Clearance in AD

closed · Rounds: 4 · Score: 0.75 · 2026-04-27

Hypothesis debate: TREM2-Mediated Microglial Dysfunction Disrupts Perivascular T

closed · Rounds: 4 · Score: 0.50 · 2026-04-27

Hypothesis debate: C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

closed · Rounds: 4 · Score: 0.58 · 2026-04-27

Hypotheses created for system testing (hyp_test_* prefix)

closed · Rounds: 4 · Score: 0.77 · 2026-04-26

Hypothesis debate: PLCG2 Allosteric Modulation as a Precision Therapeutic for TR

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: PLCG2 Allosteric Modulation as a Precision Therapeutic for TR

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

Hypothesis debate: TREM2-Dependent Microglial Senescence Transition

closed · Rounds: 4 · Score: 0.64 · 2026-04-26

Hypothesis debate: TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegene

closed · Rounds: 4 · Score: 0.50 · 2026-04-26

What are the key mechanistic, therapeutic, and diagnostic dimensions of TREM2 in

closed · Rounds: 4 · Score: 0.92 · 2026-04-26

Related Research

Hypotheses and analyses mentioning SYK in their description or question text

TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocytic Clearance

Score: 0.453 · neuroinflammation · 2026-04-13

## Mechanistic Overview TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocytic Clearance starts from the claim

Selective SYK Inhibition for Neuroprotective Microglia

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

Partial SYK modulation to enhance TREM2-dependent phagocytosis while reducing inflammatory activation in microglia Deba

SYK

Understanding Entity Pages

Summary

Wiki Pages (6)

SYK Gene

TREM2-SYK Signaling Cascade

SYK Kinase in Microglial Activation and Alzheimer's Disease

SYK Kinase in Microglial Activation and Alzheimer's Disease

SYK Kinase Inhibitor Therapy for Neurodegeneration

SYK Protein

Pathway Diagram

Outgoing (222)

Incoming (157)

Targeting Hypotheses (7)

Mentioning Analyses (12)

TREM2 in Alzheimer's Disease: Mechanisms, Therapeutics, and Biomarkers

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Why is TYROBP deficiency neuroprotective when TYROBP is an adapter for multiple

Can biased TREM2 agonists selectively activate DAP12-SYK-PI3K without triggering

Can TREM2 receptor switching from agonism to antagonism be achieved safely witho

Does SYK activation provide neuroprotection or exacerbate neuroinflammation in e

What determines organelle-specific autophagy selectivity in neurodegenerative di

What are the specific pathophysiological mechanisms underlying uncommon immune-m

Which cell types show the most significant expression changes for neurodegenerat

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

TREM2 agonism vs antagonism in DAM microglia

Test Hypothesis Fixtures

Experiments (0)

Related Papers (8)

Debates (20)

Extended debate: TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegenera

Debate: TREM2 Microglial Activation Rescues Amyloid Clearance in AD

Hypothesis debate: TREM2-Mediated Microglial Dysfunction Disrupts Perivascular T

Hypothesis debate: C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

Hypotheses created for system testing (hyp_test_* prefix)

Hypothesis debate: PLCG2 Allosteric Modulation as a Precision Therapeutic for TR

Hypothesis debate: PLCG2 Allosteric Modulation as a Precision Therapeutic for TR

Hypothesis debate: TREM2-Dependent Microglial Senescence Transition

Hypothesis debate: TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegene

What are the key mechanistic, therapeutic, and diagnostic dimensions of TREM2 in

Related Research

TREM2-SYK Signaling Axis Couples OxPC Recognition to Phagocytic Clearance

Selective SYK Inhibition for Neuroprotective Microglia