gene

CS

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about CS: 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.

48Connections
30Hypotheses
13Analyses
40Outgoing
8Incoming
5Experiments
17Debates

Summary

CS encodes citrate synthase, a key mitochondrial enzyme in the TCA cycle with important roles in neuronal energy metabolism and neurodegeneration.

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🧬 Gene Info
Gene SymbolCS
Full NameCitrate Synthase
Chromosome12p15
Protein TypeEnzyme
Functionis a nuclear-encoded gene located on chromosome 12p15 that encodes citrate synthase, a key mitochondrial enzyme that catalyzes the first committed step of the citric acid cycle (TCA cycle).
Primary Expressionvirtually all tissues with high activity in: - Heart: Highest expression (high energy demand) - Liver: Central metabolic hub - Kidney: Act
Amino Acids466 aa
UniProt IDO75390
NCBI Gene ID1451
Ensembl IDENSG00000143228
OMIM118950
GeneCardsCS
Human Protein AtlasCS
N-terminal domainContains the binding site for acetyl-CoA
C-terminal domainContains the oxaloacetate binding site
Associated DiseasesHuntington's disease, neurodegeneration
Known Drugs/Compoundsquercetin, rapamycin
InteractionsAKT, BDNF, CALCOCO2, CDKN1A, CDKN2A, CXCL1
KG Connections48 knowledge graph edges
DatabasesGeneCardsHPASTRING
🔮 Predicted Structure: CS — AlphaFold O75390 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

CS Gene

gene · 798 words

Validated Hypothesis: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and block tau propagation via perforant path in AD

hypothesis · 5450 words

Validated Hypothesis: 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Disease-Associated Microglia

hypothesis · 4761 words

Validated Hypothesis: ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degeneration in Alzheimer's Disease

hypothesis · 4717 words

Validated Hypothesis: ACSL4-Driven Ferroptotic Priming in Disease-Associated Microglia

hypothesis · 4709 words

Validated Hypothesis: CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion

hypothesis · 4553 words

Pathway Diagram

flowchart TD
    N0["CS"]
    N1["neurodegeneration"]
    N0 -->|"associated with"| N1
    N2["PINK1"]
    N0 -->|"activates"| N2
    N3["PRKN"]
    N0 -->|"activates"| N3
    N4["senescence"]
    N0 -->|"participates in"| N4
    N5["CXCL1"]
    N0 -->|"activates"| N5
    N6["CXCL8"]
    N0 -->|"activates"| N6
    N7["GLB1"]
    N0 -->|"activates"| N7
    N8["LC3"]
    N0 -->|"activates"| N8

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    classDef protein fill:#1a2a3a,stroke:#4fc3f7,color:#e0e0e0
    classDef disease fill:#3a1a1a,stroke:#ef5350,color:#e0e0e0
    classDef pathway fill:#2a1a3a,stroke:#ce93d8,color:#e0e0e0
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    classDef therapeutic fill:#1a2a2a,stroke:#26c6da,color:#e0e0e0
    classDef index fill:#1a1a2a,stroke:#7986cb,color:#e0e0e0
    class N0 gene
    class N1 disease
    class N2 gene
    class N3 gene
    class N4 pathway
    class N5 gene
    class N6 gene
    class N7 gene
    class N8 gene

Outgoing (40)

TargetRelationTypeStr
neurodegenerationassociated_withdisease0.70
PRKNactivatesgene0.60
CXCL1activatesgene0.60
CXCL8activatesgene0.60
GLB1activatesgene0.60

Incoming (8)

SourceRelationTypeStr
AKTactivatesgene0.60
CALCOCO2activatesgene0.60
CDKN1Aactivatesgene0.60
CDKN2Aactivatesgene0.60
BDNFactivatesgene0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

HypothesisScoreDiseaseAnalysis
ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro 0.891 alzheimers Cell type vulnerability in Alzheimers Di
Closed-loop tACS targeting EC-II parvalbumin interneurons to 0.869 alzheimers Circuit-level neural dynamics in neurode
Elevated CSF/Serum Albumin Quotient Predicts Neurodegenerati 0.850 - What blood-brain barrier permeability ch
STING Antagonists as ALS Therapeutics: Drug Repurposing 0.821 neuroinflammation How does chronic cGAS/STING activation d
HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43 0.820 neurodegeneration What is the therapeutic window between i
Closed-loop tACS targeting EC-II PV interneurons to suppress 0.811 alzheimers Circuit-level neural dynamics in neurode
CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion 0.808 neurodegeneration TREM2 agonism vs antagonism in DAM micro
Integrated Multi-Analyte CSF Panel Combining YKL-40, sTREM2, 0.807 biomarkers What biomarkers can reliably detect micr
CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Wind 0.801 neuroimmunology TREM2 in Alzheimer's Disease: Mechanisms
ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drive 0.801 alzheimers Cell type vulnerability in Alzheimers Di
40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Pri 0.801 alzheimers Cell type vulnerability in Alzheimers Di
Selective APOE4 Degradation via Proteolysis Targeting Chimer 0.795 neurodegeneration APOE4 structural biology and therapeutic
Senescent Microglia Resolution via Maresins-Senolytics Combi 0.791 neurodegeneration Neuroinflammation resolution mechanisms
Closed-loop tACS targeting entorhinal cortex layer II SST in 0.784 alzheimers Circuit-level neural dynamics in neurode
ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligo 0.779 alzheimers Cell type vulnerability in Alzheimers Di
Closed-loop tACS targeting EC-II SST interneurons to block t 0.752 alzheimers Circuit-level neural dynamics in neurode
Tau/MAP6 ratio as a master switch for microtubule dynamics p 0.750 neurodegeneration -
TREM2-CSF1R Cross-Talk in Microglial Metabolic Reprogramming 0.748 neurodegeneration Gene expression changes in aging mouse b
KCNQ2/3 (M-current) Channel Restoration Reactivates Theta Os 0.725 alzheimers Closed-loop optogenetic targeting PV int
TDP-43 condensation thermodynamics as a therapeutic target a 0.724 neuroscience How can subcellular compartmentalization
CSF YKL-40 as a Priming-Specific Chitinase Marker 0.723 biomarkers What biomarkers can reliably detect micr
Interfacial Lipid Mimetics to Disrupt Domain Interaction 0.723 neurodegeneration APOE4 structural biology and therapeutic
ACSL4 lipid remodeling creates ferroptosis-prone ALS membran 0.710 neurodegeneration Ferroptosis in ALS motor neuron vulnerab
CSF/Plasma AQP4 Polarization Index as a Novel Biomarker of A 0.705 - What blood-brain barrier permeability ch
CSF Soluble TREM2 Fragment Ratio as Priming State Indicator 0.689 biomarkers What biomarkers can reliably detect micr
Lysosomal Positioning Dynamics Modulation 0.686 neurodegeneration Autophagy-lysosome pathway convergence a
GPX4 Selenopeptide Mimetics as Neuroprotective Ferroptosis B 0.680 - Ferroptosis in ALS and motor neuron dise
Matrix Metalloproteinase-9/TIMP-1 Ratio in CSF Identifies Pr 0.675 - What blood-brain barrier permeability ch
Lipid Droplet Dynamics as Phenotype Switches 0.666 neurodegeneration Astrocyte reactivity subtypes in neurode
eIF2α Phosphorylation Imbalance Disrupts Mitochondrial Prote 0.000 als -

Mentioning Analyses (13)

Scientific analyses that reference this entity

Microglial Priming as Upstream Causal Node Across AD, PD, ALS, MS: Three-Arm Cau

neurodegeneration | 2026-04-27 | 3 hypotheses Top: 0.604

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.585

What blood-brain barrier permeability changes serve as early biomarkers for neur

neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.940

What blood-brain barrier permeability changes serve as early biomarkers for neur

neurodegeneration | 2026-04-26 | 8 hypotheses Top: 0.745

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

neurodegeneration | 2026-04-26 | 3 hypotheses Top: 0.362

Experiments (5)

Experimental studies targeting or related to this entity

ExperimentTypeDiseaseScoreFeasibilityModelStatusEst. Cost
SAHA@LIPO-ANG2 therapeutic efficacy in 5xFAD mice validation Alzheimer's disease 0.900 0.00 5xFAD transgenic mice proposed N/A
Transcriptomic profiling and differential expression analysis exploratory Alzheimer's disease 0.900 0.00 1-month-old APP/PS1 mice cereb proposed N/A
Autophagy receptor identification for stress granule elimination exploratory neurodegenerative diseases 0.900 0.00 cultured cells under arsenite proposed N/A
SIRPα modulation in mouse models of Alzheimer's disease validation Alzheimer's disease 0.900 0.00 mouse models of Alzheimer's di proposed N/A
Microglial SIRPα expression in human Alzheimer's disease tissue exploratory Alzheimer's disease 0.800 0.00 human brain tissue proposed N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMIDAuthorsJournalYearCitations
Transcriptomic cytoarchitecture reveals principles of human neocortex organizati [PMID:37824655] Jorstad NL, Close J, Johansen N, Yanny A Science 2023 186
FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression. [PMID:41862445] Qin J, Ma S, Wang J, Huang S, Luan J, He Cell death & disease 2026 0
Quercetin attenuates ox-LDL-induced endothelial injury by regulating ferroptosis [PMID:41902795] Gao C, Liu B, Zhang R, Tian J, Xin H Toxicology mechanisms and meth 2026 0
Activation of stimulator of interferon genes (STING) and inhibition of vascular [PMID:41380972] Wang Y, Hou Y, Han J, Zhang Z, Cheng Y e J Biol Chem 2026 0
cGAS-STING signaling in Alzheimer's disease: Microglial mechanisms and therapeut [PMID:41481960] Fazal F, Dar NJ, Ahamad S, Khan S, Bano Mol Aspects Med 2026 0
Opportunities and challenges of targeting cGAS-STING in cancer. [PMID:41486397] Lu C, Wang W, Fu YX Nat Rev Cancer 2026 0
cGAS-STING activation in Parkinson's Disease: From mechanisms to Disease-Modifyi [PMID:41500413] Solomon J, Mandal S, Aran KR Gene 2026 0
NEDD8 promotes the ferritinophagy and ferroptosis of neurons in ischemic stroke [PMID:41662890] Rao W, Huang Y, Li J, Chen Q, Sun J et a J Stroke Cerebrovasc Dis 2026 0
Inhibition of Ferroptosis in Prostatitis Model by Low Intensity Extracorporeal S [PMID:41714892] Lin D, Li K, Kuang W, Chen Z, Zhang M World J Mens Health 2026 0
STING-NF-κB signaling builds an influenza spillover barrier. [PMID:41747053] Ye R, Wang S, Hu Y, Pan Y, Zheng W et al Science 2026 0
Deciphering sorafenib resistance in hepatocellular carcinoma via ferroptotic mec [PMID:41763496] Che L, Zhu L, Zhou L, Zhou Y Biochim Biophys Acta Rev Cance 2026 0
The cGAS-STING signaling pathway: A central regulator and novel therapeutic targ [PMID:41765111] Jiang H, Ji Y, Shang T, Qi L, Li Z et al Biochem Pharmacol 2026 0
B4GALT1 deficiency attenuates steatohepatitis by regulating the PPARγ/ACSL4 axis [PMID:41860570] Chien Y, Xia R, Zhou D, Ai Y, Wu L et al Hepatol Commun 2026 0
cGAS-STING and PANoptosis: Interplay, Underlying Mechanisms, and Therapeutic Tar [PMID:42016387] Wang Y, Chen J, Feng W, Li N, Zhang X et Drug Des Devel Ther 2026 0
Unraveling the impact of risk factors on the ferroptosis-Alzheimer's disease lin [PMID:41498558] Singh P, Rath SL Journal of Alzheimer's disease 2026 0
Resveratrol Alleviates Intervertebral Disc Degeneration by Targeting NCOA4-Media [PMID:41873334] Song C, Wu X, Chen C, Shen B, He Y, Liu Drug design, development and t 2026 0
Pan-PPAR agonist bezafibrate alleviates psoriasis by suppressing LCN2-dependent [PMID:41662914] ["Xin R", "Zhang J", "Zhang Y", "Dai M", Free radical biology & medicin 2026 0
Acteoside alleviates sepsis-induced acute lung injury by activating the Nrf2 pat [PMID:41895086] Wang Y, Zhang W, Zhang M, Zhu Y, Wang W, Tissue & cell 2026 0
Ferroptosis and microglial polarization in retinal vein occlusion: pathological [PMID:41924362] Xu J, Sun M, Wang C, Ju P, Guan XD, Xie International journal of ophth 2026 0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810] ["Chen Kai", "Li Fuyao", "Zhang Shuwen", Journal of neuroinflammation 2025 0

Debates (17)

Multi-agent debates referencing this entity

Is microglial priming (TREM2/CX3CR1/complement-C1q) genuinely causally upstream

closed · Rounds: 4 · Score: 0.64 · 2026-04-28

What is the evidence that blood-brain barrier (BBB) permeability changes serve a

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Can CSF p-tau217 normalization serve as a reliable surrogate endpoint for determ

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Formal debate: plasma GFAP separates causal from compensatory states in: Blood-b

closed · Rounds: 3 · Score: 0.75 · 2026-04-26

Formal debate: tight-junction remodeling is the actionable driver in: Blood-brai

closed · Rounds: 3 · Score: 0.75 · 2026-04-26

What blood-brain barrier permeability changes serve as early biomarkers for neur

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

What blood-brain barrier permeability changes serve as early biomarkers for neur

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

closed · Rounds: 4 · Score: 0.78 · 2026-04-26

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

closed · Rounds: 7 · Score: 0.50 · 2026-04-26

Which specific CSF molecular components are essential for maintaining disease-re

closed · Rounds: 4 · Score: 0.66 · 2026-04-25

Related Research

Hypotheses and analyses mentioning CS in their description or question text

Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and bl

Score: 0.811 · alzheimers · 2026-04-05

## Mechanistic Overview Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and block tau propagat

CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion

Score: 0.808 · neurodegeneration · 2026-04-16

## Mechanistic Overview CSF1R-TREM2 Co-Agonism for Sustained Microglial Expansion starts from the claim that modulating

Integrated Multi-Analyte CSF Panel Combining YKL-40, sTREM2, and Neurogranin

Score: 0.807 · biomarkers · 2026-04-22

## Mechanistic Overview Integrated Multi-Analyte CSF Panel Combining YKL-40, sTREM2, and Neurogranin starts from the cla

CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window Identification

Score: 0.801 · neuroimmunology · 2026-04-15

## Mechanistic Overview CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window Identification starts from the cl

ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degen

Score: 0.801 · alzheimers · 2026-04-05

## Mechanistic Overview ACSL4-Ferroptotic Priming in Stressed Oligodendrocytes Drives White Matter Degeneration in Alzhe

40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively

Score: 0.801 · alzheimers · 2026-04-05

## Mechanistic Overview 40 Hz Gamma Entrainment Gates ACSL4-Mediated Ferroptotic Priming to Selectively Eliminate Diseas

Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)

Score: 0.795 · neurodegeneration · 2026-04-02

## Mechanistic Overview Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs) starts from the claim t

Senescent Microglia Resolution via Maresins-Senolytics Combination

Score: 0.791 · neurodegeneration · 2026-04-02

## Mechanistic Overview Senescent Microglia Resolution via Maresins-Senolytics Combination starts from the claim that mo

Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activa

Score: 0.784 · alzheimers · 2026-04-05

## Mechanistic Overview Closed-loop tACS targeting entorhinal cortex layer II SST interneurons to activate AMPK-autophag

ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlie

Score: 0.779 · alzheimers · 2026-04-05

## Mechanistic Overview ACSL4-Driven Ferroptotic Priming in Disease-Associated Oligodendrocytes Underlies White Matter D

Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and r

Score: 0.752 · alzheimers · 2026-04-05

## Mechanistic Overview Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and restore perforant

TREM2-CSF1R Cross-Talk in Microglial Metabolic Reprogramming

Score: 0.748 · neurodegeneration · 2026-04-12

**Molecular Mechanism and Rationale** The TREM2-CSF1R metabolic cross-talk hypothesis centers on the intricate molecula

KCNQ2/3 (M-current) Channel Restoration Reactivates Theta Oscillation Dynamics

Score: 0.725 · alzheimers · 2026-04-28

Aβ oligomers downregulate KCNQ2/3 voltage-gated potassium channels on PV interneurons via PKC-dependent phosphorylation,

TDP-43 condensation thermodynamics as a therapeutic target and biomarker for nuc

Score: 0.724 · neuroscience · 2026-04-26

FRAP-based measurement of TDP-43 liquid-liquid phase separation state provides a continuous biomarker of nuclear-cytopla