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.

86Connections

2Hypotheses

1Analyses

50Outgoing

25Incoming

No summary available yet. View on Wiki →

💡 Concept Info

Name	HMGCS2
Key Genes/Proteins	TJP1
Related Diseases	Stroke, Neuroinflammation, Als, Cancer, Neurodegeneration
Related Pathways	Epigenetic, Blood-Brain Barrier
Linked Hypotheses	1 hypotheses

Wiki Pages (12)

Knowledge base pages for this entity

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 (61)

Target	Relation	Type	Str
Stroke	inhibits	disease	0.65
Neuroinflammation	activates	disease	0.65
Als	regulates	disease	0.65
Cancer	regulates	disease	0.65
Neurodegeneration	regulates	disease	0.65
Diabetes	regulates	disease	0.65
Inflammation	activates	disease	0.65
ALS	regulates	disease	0.65
Inflammation	regulates	disease	0.65
TJP1	activates	gene	0.60
Epigenetic	activates	pathway	0.60
Blood-Brain Barrier	activates	pathway	0.60
Endothelial	inhibits	cell_type	0.60
Epigenetic	regulates	pathway	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
Rb	inhibits	protein	0.60
Fus	activates	protein	0.60
endothelial cells	inhibits	cell_type	0.60
endothelial cells	expressed_in	cell_type	0.60
endothelial cells	disrupts	cell_type	0.60
MCT1	interacts_with	gene	0.60
autophagy pathway	participates_in	pathway	0.60
SNCA	co_mentioned	gene	0.55
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
neurodegeneration	associated_with	disease	0.50
Stroke	associated_with	disease	0.50
MTOR	debate_co_mention	gene	0.45
NAMPT	debate_co_mention	gene	0.45
neuroinflammation	debate_co_mention	process	0.45
oxidative stress	debate_co_mention	process	0.45
TFEB	debate_co_mention	gene	0.45
TFEB	co_discussed	gene	0.40
PRKAA1	co_discussed	gene	0.40
NAMPT	co_discussed	gene	0.40
CLOCK	co_discussed	gene	0.40
GLUT4	co_discussed	gene	0.40
GLUT3	co_discussed	gene	0.40

Incoming (25)

Source	Relation	Type	Str
h-4b517512	targets_gene	hypothesis	0.90
h-edfd6c89	targets_gene	hypothesis	0.90
h-5626c1f2	targets_gene	hypothesis	0.90
FAS	activates	gene	0.60
STROKE	inhibits	gene	0.60
GPR109A	regulates	gene	0.60
EXERCISE	regulates	gene	0.60
NEUROINFLAMMATION	activates	gene	0.60
AND	inhibits	gene	0.60
TJP1	activates	gene	0.60
NEURODEGENERATION	regulates	gene	0.60
Β-HYDROXYBUTYRATE	regulates	gene	0.60
INFLAMMATION	regulates	gene	0.60
AND	associated_with	gene	0.60
CANCER	regulates	gene	0.60
GFAP	activates	gene	0.55
ALS	activates	gene	0.55
APP	protects_against	gene	0.55
ATP	associated_with	gene	0.55
APP	targets	gene	0.55
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 (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Temporal Metabolic Window Therapy	0.506	neurodegeneration	How do astrocyte-neuron metabolic intera
The Glial Ketone Metabolic Shunt Hypothesis	0.398	neurodegeneration	Metabolic reprogramming in neurodegenera

Mentioning Analyses (1)

Scientific analyses that reference this entity

Metabolic reprogramming in neurodegenerative disease

neurodegeneration | 2026-04-02 | 3 hypotheses Top: 0.398

Related Papers (13)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
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
HMGCS2-dependent β-OHB/H3K9bhb ameliorates synaptic plasticity and cognition in [PMID:41792234]	Yu H, Wang F, Yuan JQ, Chen J, Zhang KY	Exp Mol Med	2026
Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bo [PMID:40305364]	Suresh VV, Sivaprakasam S, Bhutia YD, Pr	Biomolecules	2025
Computational Screening of Repurposed Drugs for HMG-CoA Synthase 2 in Alzheimer' [PMID:38875044]	Shamsi A, Furkan M, Khan MS, Yadav DK, S	J Alzheimers Dis	2024
HMGCS2-Induced Autophagic Degradation of Tau Involves Ketone Body and ANKRD24. [PMID:36442191]	Hu LT, Xie XY, Zhou GF, Wen QX, Song L e	J Alzheimers Dis	2023
[WALANT - Wide Awake Local Anaesthesia No Tourniquet: Complications in elective [PMID:35168268]	Wieschollek S, Forster S, Megerle K	Handchirurgie, Mikrochirurgie,	2022
Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis. [PMID:35421611]	Asif S, Kim RY, Fatica T, Sim J, Zhao X	Mol Metab	2022
Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Bo [PMID:34456688]	["Li\u015bkiewicz D", "Li\u015bkiewicz A	Frontiers in cellular neurosci	2021
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
Engineering complex communities by directed evolution. [PMID:33986540]	Chang CY, Vila JCC, Bender M, Li R, Mank	Nature ecology & evolution	2021
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
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
HMGCS2 promotes autophagic degradation of the amyloid-β precursor protein throug [PMID:28320515]	Hu LT, Zhu BL, Lai YJ, Long Y, Zha JS et	Biochem Biophys Res Commun	2017

HMGCS2

Understanding Entity Pages

Wiki Pages (12)

Section 151: Thyroid and Metabolic Hormone Optimization in CBS/PSP

MCCC1 Gene

Glial Cell Line-Derived Neurotrophic Factor (GDNF) Therapies

SIRT5 - Sirtuin 5

SIRT3 Protein - Mitochondrial Sirtuin

SIRT5 Protein - Mitochondrial Desuccinylase

MET Protein

Metabolic Therapy for Neurodegenerative Diseases

SIRT3 - Sirtuin 3

Ketone Body Therapy for Neurodegenerative Diseases

Datasets