concept

HMGCS2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about HMGCS2: 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.

90Connections

7Hypotheses

5Analyses

50Outgoing

25Incoming

6Experiments

5Debates

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💡 Concept Info

Name	HMGCS2
Key Genes/Proteins	APP, ATP, CANCER, CLOCK
Related Diseases	als, Als, ALS, cancer, Cancer
Related Pathways	autophagy, autophagy pathway, Blood-Brain Barrier
Linked Hypotheses	3 hypotheses

Pathway Diagram

graph TD
    HMGCS2["HMGCS2"]
    HMGCS2 -->|"inhibits"| Stroke["Stroke"]
    HMGCS2 -->|"activates"| Neuroinflammation["Neuroinflammation"]
    HMGCS2 -->|"regulates"| Als["Als"]
    HMGCS2 -->|"regulates"| Cancer["Cancer"]
    HMGCS2 -->|"regulates"| Neurodegeneration["Neurodegeneration"]
    HMGCS2 -->|"regulates"| Diabetes["Diabetes"]
    HMGCS2 -->|"activates"| Inflammation["Inflammation"]
    HMGCS2 -->|"regulates"| ALS["ALS"]
    FAS["FAS"] -->|"activates"| HMGCS2
    STROKE["STROKE"] -->|"inhibits"| HMGCS2
    GPR109A["GPR109A"] -->|"regulates"| HMGCS2
    EXERCISE["EXERCISE"] -->|"regulates"| HMGCS2
    NEUROINFLAMMATION["NEUROINFLAMMATION"] -->|"activates"| HMGCS2
    AND["AND"] -->|"inhibits"| HMGCS2
    TJP1["TJP1"] -->|"activates"| HMGCS2
    NEURODEGENERATION["NEURODEGENERATION"] -->|"regulates"| HMGCS2

Outgoing (65)

Target	Relation	Type	Str
Astrocyte ketogenesis	regulates	process	0.90
ketogenic flux	regulates	pathway	0.70
Neuroinflammation	activates	disease	0.65
Stroke	inhibits	disease	0.65
ALS	regulates	disease	0.65
Inflammation	regulates	disease	0.65
Inflammation	activates	disease	0.65
Als	regulates	disease	0.65
Cancer	regulates	disease	0.65
Neurodegeneration	regulates	disease	0.65
Diabetes	regulates	disease	0.65
Epigenetic	regulates	pathway	0.60
Blood-Brain Barrier	activates	pathway	0.60
Endothelial	inhibits	cell_type	0.60
TJP1	activates	gene	0.60
Epigenetic	activates	pathway	0.60
endothelial cells	disrupts	cell_type	0.60
MCT1	interacts_with	gene	0.60
autophagy pathway	participates_in	pathway	0.60
endothelial cells	inhibits	cell_type	0.60
Fus	activates	protein	0.60
endothelial cells	expressed_in	cell_type	0.60
Rb	inhibits	protein	0.60
STROKE	inhibits	gene	0.60
FAS	activates	gene	0.60
EXERCISE	regulates	gene	0.60
GPR109A	regulates	gene	0.60
Insulin	regulates	protein	0.60
astrocytes	expressed_in	cell_type	0.55
insulin signaling	participates_in	pathway	0.55
unfolded protein response	participates_in	pathway	0.55
oxidative stress response	participates_in	pathway	0.55
PS1	protects_against	gene	0.55
neurons	expressed_in	cell_type	0.55
PS1	targets	gene	0.55
SNCA	targets	gene	0.55
SOD1	targets	gene	0.55
neurodegeneration	targets	disease	0.55
SNCA	co_mentioned	gene	0.55
Stroke	associated_with	disease	0.50
neurodegeneration	associated_with	disease	0.50
neuroinflammation	debate_co_mention	process	0.45
oxidative stress	debate_co_mention	process	0.45
TFEB	debate_co_mention	gene	0.45
MTOR	debate_co_mention	gene	0.45
NAMPT	debate_co_mention	gene	0.45
NAMPT	co_discussed	gene	0.40
CLOCK	co_discussed	gene	0.40
GLUT4	co_discussed	gene	0.40
TFEB	co_discussed	gene	0.40

Incoming (25)

Source	Relation	Type	Str
h-4b517512	targets_gene	hypothesis	0.90
h-5626c1f2	targets	hypothesis	0.90
h-edfd6c89	targets_gene	hypothesis	0.90
NEURODEGENERATION	regulates	gene	0.60
Β-HYDROXYBUTYRATE	regulates	gene	0.60
INFLAMMATION	regulates	gene	0.60
CANCER	regulates	gene	0.60
TJP1	activates	gene	0.60
NEUROINFLAMMATION	activates	gene	0.60
FAS	activates	gene	0.60
STROKE	inhibits	gene	0.60
GPR109A	regulates	gene	0.60
EXERCISE	regulates	gene	0.60
ALS	activates	gene	0.55
ATP	associated_with	gene	0.55
APP	targets	gene	0.55
APP	protects_against	gene	0.55
GFAP	activates	gene	0.55
h-2f3fa14b	targets	hypothesis	0.50
h-6df1bc66	targets	hypothesis	0.50
autophagy	debate_co_mention	pathway	0.45
CLOCK	debate_co_mention	gene	0.45
GLUT3/GLUT4	debate_co_mention	gene	0.45
GLUT3	co_discussed	gene	0.40
SIRT5 Protein - Mitochondrial Desuccinylase	references	protein	0.40

Targeting Hypotheses (7)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Ketone Utilization Index as Metabolic Flexibility Biomarker	0.829	translational neuroscience	Which metabolic biomarkers can distingui
Biphasic Ketogenic Intervention Protocol	0.780	metabolic neuroscience	What determines the optimal timing and d
The Glial Ketone Metabolic Shunt Hypothesis	0.608	neurodegeneration	Metabolic reprogramming in neurodegenera
Temporal Metabolic Window Therapy	0.525	neurodegeneration	How do astrocyte-neuron metabolic intera
Enhancement of Astrocytic Ketone Body Production via HMGCS2	0.380	metabolomics	Metabolomic signatures of neurodegenerat

Enhancement of Astrocytic Ketone Body Production via HMGCS2	0.380	metabolomics	Metabolomic signatures of neurodegenerat
Astrocyte Fuel Preference Pharmacogenomics	0.000	-	How do astrocyte-neuron metabolic intera

Mentioning Analyses (5)

Scientific analyses that reference this entity

What are the precise temporal dynamics of astrocyte ketone production decline du

neurodegeneration | 2026-04-15 | 2 hypotheses Top: 0.808

Which metabolic biomarkers can distinguish therapeutic response from disease pro

translational neuroscience | 2026-04-04 | 10 hypotheses Top: 0.829

How do astrocyte-neuron metabolic interactions change during disease progression

neurodegeneration | 2026-04-04 | 7 hypotheses Top: 0.541

What determines the optimal timing and dosing of ketogenic interventions for neu

metabolic neuroscience | 2026-04-03 | 7 hypotheses Top: 0.780

Metabolic reprogramming in neurodegenerative disease

neurodegeneration | 2026-04-02 | 3 hypotheses Top: 0.652

Experiments (6)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
AECII-specific HMGCS2 overexpression in mouse pulmonary fibrosis	validation	idiopathic pulmonary fibrosis	0.950	C57BL/6 mice with AECII-specif	proposed	N/A
Mobile App-Based Intervention for BPSD in Community-Dwelling Dementia	clinical	dementia with behavioral and p	0.950	human patients	proposed	N/A
HMGCS2 gain-of-function in AECII lipid metabolism regulation	exploratory	idiopathic pulmonary fibrosis	0.900	human AECIIs	proposed	N/A
Ketogenic diet fat threshold analysis in wild-type mice	validation	metabolic disease	0.900	C57BL/6J wild-type mice	proposed	N/A
Ketogenic diet efficacy in diet-induced obese mice	validation	obesity, metabolic disease	0.900	C57BL/6J diet-induced obese mi	proposed	N/A
Microarray and single-cell RNA analysis of lipid metabolism genes	exploratory	idiopathic pulmonary fibrosis	0.850	human patients, mouse models	proposed	N/A

Related Papers (18)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS [PMID:33031745]	Yu CH, Davidson S, Harapas CR, Hilton JB	Cell	2020	2
HMGCS2 desuccinylation modulates acetoacetate to drive tubule-macrophage inflamm [PMID:41580118]	Lin Z, Lv D, Zha H, Liu H, Peng R et al.	Metabolism	2026	0
Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bo [PMID:40305364]	Suresh VV, Sivaprakasam S, Bhutia YD, Pr	Biomolecules	2025	0
Air pollution, glymphatic impairment, and Alzheimer's disease. [PMID:37777345]	Hussain R, Graham U, Elder A, Nedergaard	Trends in neurosciences	2023	0
Roles of neuropathology-associated reactive astrocytes: a systematic review. [PMID:36915214]	Lawrence JM, Schardien K, Wigdahl B, Non	Acta neuropathologica communic	2023	0
[WALANT - Wide Awake Local Anaesthesia No Tourniquet: Complications in elective [PMID:35168268]	Wieschollek S, Forster S, Megerle K	Handchirurgie, Mikrochirurgie,	2022	0
Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Bo [PMID:34456688]	["Li\u015bkiewicz D", "Li\u015bkiewicz A	Frontiers in cellular neurosci	2021	0
Complete Genome Sequence of Geobacter sp. Strain FeAm09, a Moderately Acidophili [PMID:33446582]	Yadav P, Antony-Babu S, Hayes E, Healy O	Microbiology resource announce	2021	0
Engineering complex communities by directed evolution. [PMID:33986540]	Chang CY, Vila JCC, Bender M, Li R, Mank	Nature ecology & evolution	2021	0
Successful Nonoperative Treatment of Osteochondritis Dissecans of the Humeral Ca [PMID:34825100]	Tajika T, Kuboi T, Endo F, Hatori Y, Sai	Progress in rehabilitation med	2021	0
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS [PMID:33031745]	Yu CH, Davidson S, Harapas CR, Hilton JB	Cell	2020	0
Improved tools to study astrocytes. [PMID:32042146]	Unknown	Nat Rev Neurosci	2020	0
Genome-Wide Screen of the Hippocampus in Aged Rats Identifies Mitochondria, Meta [PMID:32457595]	["Wang Y", "Qian M", "Qu Y", "Yang N", "	Frontiers in aging neuroscienc	2020	0
Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced m [PMID:29400714]	Shi Y, Lin S, Staats KA, Li Y, Chang WH,	Nature medicine	2018	0
Monoaminergic neuropathology in Alzheimer's disease. [PMID:27084356]	Unknown	Prog Neurobiol	2017	0
Algal photoreceptors: in vivo functions and potential applications. [PMID:24081482]	Unknown	Planta	2014	0
Neurobiology of food intake in health and disease. [PMID:24840801]	Morton Gregory J; Meek Thomas H; Schwart	Nature reviews. Neuroscience	2014	0
An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells [PMID:20413890]	Unknown	J Alzheimers Dis	2010	0