gene

HK2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about HK2: 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.

813Connections

3Hypotheses

3Analyses

50Outgoing

50Incoming

6Experiments

3Debates

Summary

HK2 is a gene implicated in neurodegeneration research. Key relationships include: activates, inhibits, therapeutic target. Associated with ALS, Aging, Als. Connected to 408 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	HK2
Full Name	Hexokinase 2
Chromosome	2p12
Protein Type	Enzyme
Target Class	Enzyme
Function	Small molecule inhibitor of glucose phosphorylation
Mechanism of Action	Small molecule inhibitor of glucose phosphorylation
Primary Expression	Brain, Muscle, Fat
Druggability	Low (0.38)
Clinical Stage	Phase III
Pathways	Akt, Apoptosis, Epigenetic, Erk Signaling, Glucose Metabolism
UniProt ID	P19367
NCBI Gene ID	3099
Ensembl ID	ENSG00000149718
GeneCards	HK2
Human Protein Atlas	HK2
Associated Diseases	Acute Kidney Injury, Als, Alzheimer, Alzheimer's disease, Cancer
Known Drugs/Compounds	aducanumab, ADUCANUMAB
Interactions	ABCA1, ACC, ACLY, ACSL4, ACSL5, Actin
SciDEX Target	View Target Profile (10 clinical trials)
SciDEX Hypotheses	HK2-Dependent Metabolic Checkpoint as the Gatekeep Metabolic Switch Targeting for A1→A2 Repolarizatio Metabolic Reprogramming via Microglial Glycolysis
KG Connections	813 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — HK2 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

2NZT — X-ray / Cryo-EM

🔮 AI Predicted Structure

P19367 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

HK2

gene · 1954 words

→

HK2 Protein — Hexokinase 2

protein · 637 words

→

Pathway Diagram

graph TD
    HK2["HK2"] -->|"associated"| neurodegeneration["neurodegeneration"]
    HK2["HK2"] -->|"co discussed"| MIRO1["MIRO1"]
    HK2["HK2"] -->|"co discussed"| P2RY1["P2RY1"]
    HK2["HK2"] -->|"co discussed"| SOAT1["SOAT1"]
    HK2["HK2"] -->|"co discussed"| KCNK2["KCNK2"]
    HK2["HK2"] -->|"co discussed"| TET2["TET2"]
    BMAL1["BMAL1"] -->|"co discussed"| HK2["HK2"]
    style HK2 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (560)

Target	Relation	Type	Str
Cancer	activates	disease	1.00
Glycolysis	activates	pathway	1.00
CANCER	activates	gene	1.00
GLYCOLYSIS	involved_in	entity	0.95
glycolysis	drives	pathway	0.95
Tumor	activates	disease	0.95
Ubiquitin-Proteasome System	associated_with	pathway	0.95
VDAC	interacts_with	protein	0.95
Metabolic Stress	mediates	process	0.95
Histone Lactylation	mediates	mechanism	0.95
Hepatic Stellate Cell Activation	associated_with	process	0.95
mitophagy	regulates	process	0.92
MITOCHONDRIAL FUNCTION	modulates	entity	0.92
Histone Lactylation	regulates	process	0.90
Glycolysis	upregulates	pathway	0.90
Glycolysis	involved_in	process	0.90
NEURODEGENERATION	therapeutic_target	entity	0.90
MACROPHAGE	expressed_in	entity	0.90
glucose metabolism	involved_in	process	0.90
PI3K	activates	gene	0.90
GENES	activates	gene	0.90
AKT	activates	gene	0.90
Pi3K/Akt	activates	pathway	0.90
MASLD	associated_with	disease	0.88
Inflammation	upregulates	process	0.88
Lactate	associated_with	compound	0.85
Als	activates	disease	0.85
neurodegeneration	associated_with	disease	0.85
Gene Expression	regulates	process	0.85
Inflammation Burden	regulates	phenotype	0.85
Lactate Production	regulates	process	0.85
Tumor	associated_with	disease	0.85
Liver Macrophages	expressed_in	cell_type	0.85
Acute Kidney Injury	associated_with	disease	0.85
NEURODEGENERATION	associated_with	entity	0.85
Renal Ischemia-Reperfusion Injury	contributes_to	disease	0.85
Tumor Metastasis	involved_in	phenotype	0.85
inflammation	promotes	process	0.85
Metabolic Dysfunction-Associated Fatty Liver Disease	implicated_in	disease	0.85
NEUROINFLAMMATION	mediates	entity	0.85
Cancer	inhibits	disease	0.85
glucose-dependent signaling	mediates	process	0.80
AGING	associated_with	entity	0.80
Aerobic Glycolysis	involved_in	process	0.80
Lactate	regulates	compound	0.80
Acute Kidney Injury	contributes_to	disease	0.80
Renal Function	regulates	phenotype	0.80
Mtor	activates	pathway	0.80
glycolysis	rate_limits	pathway	0.80
Als	inhibits	disease	0.75

Incoming (253)

Source	Relation	Type	Str
Phds	degrades	drug	0.95
Chnds	degrades	drug	0.90
Retinitis Pigmentosa progression	downregulates	phenotype	0.90
Pi3K/Akt Pathway	phosphorylates	pathway	0.90
Glucose Metabolism	regulates	process	0.90
RGFP966	downregulates	drug	0.90
h-38292315	targets_gene	hypothesis	0.90
h-var-ac50d1e3d1	targets_gene	hypothesis	0.90
AST-120	downregulates	drug	0.90
h-a1b56d74	targets_gene	hypothesis	0.90
PINK1	interacts_with	gene	0.90
PI3K/AKT	phosphorylates	pathway	0.90
HIF1A	upregulates	gene	0.88
Mdivi-1	downregulates	drug	0.85
STAT3	upstream_of	protein	0.85
H3K18 Lactylation	upregulates	process	0.80
PAL	upregulates	compound	0.80
glucose metabolism	activates	process	0.80
h-a1b56d74	targets	hypothesis	0.80
h-38292315	targets	hypothesis	0.80
STAT3	regulates	protein	0.80
glucose metabolism	modulates	process	0.80
MYC	regulates	gene	0.80
STING	binds	gene	0.80
KLF14	inhibits	gene	0.80
PTEN	activates	gene	0.80
APOPTOSIS	activates	gene	0.70
STING	activates	gene	0.70
ASTROCYTE	activates	cell_type	0.70
MITOPHAGY	activates	gene	0.70
CANCER	inhibits	gene	0.70
HDAC3	regulates	gene	0.65
LACTATE	treats	phenotype	0.65
LACTATE	inhibits	phenotype	0.65
ROS	treats	phenotype	0.65
MTORC1	activates	gene	0.60
MAVS	interacts_with	gene	0.60
ACSL4	associated_with	gene	0.60
BAX	associated_with	gene	0.60
GPX4	associated_with	gene	0.60
glycolysis	activates	pathway	0.60
IFN	inhibits	gene	0.60
TNF-Α	inhibits	gene	0.60
NF-ΚB	regulates	gene	0.60
LDHA	activates	gene	0.60
AND	activates	gene	0.60
C-MYC	activates	gene	0.60
GLUT1	activates	gene	0.60
HIF-1Α	activates	gene	0.60
SESN2	inhibits	gene	0.60

Targeting Hypotheses (3)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
HK2-Dependent Metabolic Checkpoint as the Gatekeeper of DAM	0.919	neurodegeneration	How do different microglial subtypes (DA
Metabolic Switch Targeting for A1→A2 Repolarization	0.726	neurodegeneration	Astrocyte reactivity subtypes in neurode
Metabolic Reprogramming via Microglial Glycolysis Inhibition	0.672	neurodegeneration	Synaptic pruning by microglia in early A

Mentioning Analyses (3)

Scientific analyses that reference this entity

Experiments (6)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Proposed experiment from debate on Astrocytes adopt A1 (neurotoxic) an	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Proposed experiment from debate on Microglia activate astrocytes via I	falsification	Neuroinflammation	0.400	0.50	cell_line	proposed	$80,000
Metabolic Pathway-Targeted Therapy in ALS	clinical	ALS	0.400	0.50	human	proposed	$6,550,000
Astrocyte Ferritin Iron Metabolism Dysfunction in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
GLP-1 Agonist Responder Prediction Study — Precision Medicine for Neur	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
Metabolic Syndrome-Parkinson's Disease Axis Clinical Trial	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Saturation mutagenesis of twenty disease-associated regulatory elements at singl [PMID:31395865]	["Kircher M", "Xiong C", "Martin B", "Sc	Nature Communications	2019	267
Bergenin attenuates traumatic brain injury via inhibition of microglial PFKFB3-d [PMID:41520557]	Sun B, Zhang A, Feng S, Jamali AW, Jia Z	Int Immunopharmacol	2026	1
HK1 and HK2 Beyond Glycolysis: Mitochondrial Interactions and Dual Roles in Meta [PMID:41387352]	Pesce NA, Seminara G, Giarrusso G, Tomas	Adv Biol (Weinh)	2026	1
Glucose Metabolic Reprogramming in Microglia: Implications for Neurodegenerative [PMID:39987285]	Fang M, Zhou Y, He K, Lu Y, Tao F, Huang	Mol Neurobiol	2025	1
Hexokinase 2-mediated metabolic stress and inflammation burden of liver macropha [PMID:40014451]	Li J, Chen X, Song S, Jiang W, Geng T, W	Cell Rep	2025	1
Deficiency of Microglial Hv1 Protects Against Lipopolysaccharide-Induced Neuroin [PMID:40911376]	Sun L, Wang X, Guan S, Zhang P, Chen D,	FASEB J	2025	1
The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer. [PMID:38904014]	Fontana F, Giannitti G, Marchesi S, Limo	Int J Biol Sci	2024	1
AST-120 alleviates renal ischemia-reperfusion injury by inhibiting HK2-mediated [PMID:39217289]	Zhou J, Zhang J, Xu F, Gao H, Wang L, Zh	Mol Med	2024	1
Hexokinase 2-mediated gene expression via histone lactylation is required for he [PMID:37463576]	Rho H, Terry AR, Chronis C, Hay N	Cell Metab	2023	1
Metabolic phenotype of bladder cancer. [PMID:26975021]	Massari F, Ciccarese C, Santoni M, Iacov	Cancer Treat Rev	2016	1
Crosstalk Between [PMID:41899603]	["Ren Y", "Tang D", "Ding X", "He M"]	Cancers	2026	0
Aryl hydrocarbon receptor impairs HK2-controlled flux of the hexosamine biosynth [PMID:40582563]	Li S, Zhu J, Song J, Yang L, Gong Y et a	J Adv Res	2026	0
HDAC3 mediates retinal endothelial cell metabolic reprogramming and angiogenesis [PMID:41023273]	Mitchell CD, Morris CA, Wild M, Cunningh	Acta Pharmacol Sin	2026	0
Hypoxia-Induced Histone Lactylation Promotes Ferroptosis in Cardiomyocytes via t [PMID:41229334]	Zhu XH, Hou JW, Lv ZY, Sun MH, Zhang XY	Kaohsiung J Med Sci	2026	0
Granzyme B knockdown inhibits NLRP3-mediated pyroptosis and the JAK2/STAT3 signa [PMID:41447776]	Wang M, Chen D, Zhang D, Han H, Xie M et	Tissue Cell	2026	0
Targeting glycolysis in prostate cancer: Molecular mechanisms and therapeutic ad [PMID:41548699]	Zhang J, Zhang T, Song D, Xu D	Biochim Biophys Acta Rev Cance	2026	0
Modulation of Aerobic Glycolysis Genes During the Progression of Retinitis Pigme [PMID:41569027]	["Adani E", "Villa Vasquez S", "Lovino M	Investigative ophthalmology &	2026	0
Duzhong-Gegen formula ameliorated hyperuricemia by enhancing renal uric acid exc [PMID:41905095]	Wang L, Gan Y, Huang J, Long L, Li S, Wa	Phytomedicine : international	2026	0
From Phytochemical Characterization to Energy Metabolism-Driven Molecular Respon [PMID:41901183]	Gülüm L, Güler E, Çapkınoğlu E, Çelik AB	Nutrients	2026	0
Mitophagy bridges glucose metabolism, inflammation and neuroprotection in astroc [PMID:41677100]	["Hakansson H", "Howden J", "Kittler J"]	Autophagy	2026	0

Debates (3)

Multi-agent debates referencing this entity

HK2