gene

HDAC3

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about HDAC3: 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.

1113Connections

2Hypotheses

2Analyses

50Outgoing

50Incoming

Summary

HDAC3 is a gene implicated in neurodegeneration research. Key relationships include: regulates, activates, associated with. Associated with Aging, Als, Alzheimer. Connected to 124 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	HDAC3
Full Name	Histone Deacetylase 3
Chromosome	5q31.3.
Protein Type	Epigenetic Regulator
Target Class	Epigenetic Regulator
Function	HDAC3 encodes histone deacetylase 3, a class I histone deacetylase that catalyzes the removal of acetyl groups from lysine residues on histone proteins.
Mechanism of Action	Small molecule inhibitor of histone deacetylase enzymatic activity
Primary Expression	Ubiquitous with highest expression in brain
Druggability	Low (0.41)
Clinical Stage	Approved
Molecular Weight	33 kDa
Amino Acids	428 aa
Pathways	Autophagy, Epigenetic, Memory, Neuroprotection, Oxidative Stress
UniProt ID	O15379
Ensembl ID	ENSG00000171720
OMIM	605166
GeneCards	HDAC3
Human Protein Atlas	HDAC3
Associated Diseases	AGING, ALS, Alzheimer, Alzheimer'S Disease, Cancer
Known Drugs/Compounds	Kaempferol, H3K9, NICOTINAMIDE, RGFP966, nicotinamide, valproic acid
Interactions	TRKB, BDNF, BMAL1, NRF1, NRF2, TNF
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	Selective HDAC3 Inhibition with Cognitive Enhancem HDAC3-Selective Inhibition for Clock Reset
KG Connections	1113 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure: HDAC3 — PDB 4A69 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    HDAC3["HDAC3"]
    HDAC3 -->|"target for"| neurodegeneration["neurodegeneration"]
    HDAC3 -->|"contributes to"| Neurodegeneration["Neurodegeneration"]
    HDAC3 -->|"regulates"| Parkinson["Parkinson"]
    HDAC3 -->|"regulates"| Alzheimer["Alzheimer"]
    HDAC3 -->|"regulates"| Neuroinflammation["Neuroinflammation"]
    HDAC3 -->|"regulates"| Inflammation["Inflammation"]
    HDAC3 -->|"regulates"| Huntington["Huntington"]
    HDAC3 -->|"regulates"| Ms["Ms"]
    HDAC3 -->|"activates"| Anxiety["Anxiety"]
    h_a9571dbb["h-a9571dbb"] -->|"target for"| HDAC3
    h_0e675a41["h-0e675a41"] -->|"target for"| HDAC3
    SIRT6["SIRT6"] -->|"regulates"| HDAC3
    HDAC11["HDAC11"] -->|"expressed in"| HDAC3
    HDAC2["HDAC2"] -->|"expressed in"| HDAC3
    SIRT7["SIRT7"] -->|"regulates"| HDAC3
    SIRT5["SIRT5"] -->|"regulates"| HDAC3
    BDNF["BDNF"] -->|"regulates"| HDAC3

Outgoing (762)

Target	Relation	Type	Str
Brain Development	regulates	process	0.95
endothelial cell metabolic reprogramming	drives	process	0.95
Alzheimer'S Disease	involved_in	disease	0.95
Neurodegeneration	regulates	process	0.95
Nlrp3 Inflammasome	promotes	process	0.95
Nrf2 Signaling Pathway	mediates	pathway	0.90
NRF2	regulates	gene	0.90
Memory Formation	regulates	process	0.90
tumorigenesis	promotes	process	0.90
NLRP3	promotes	protein	0.90
histone acetylation	suppresses	process	0.90
mitochondrial fission	promotes	process	0.90
diabetic retinopathy	involved_in	disease	0.90
Pro-Inflammatory Cytokines	regulates	protein	0.90
Tumor Progression	involved_in	process	0.90
epigenetic regulation	participates_in	pathway	0.90
neural stem cells	inhibits	cell_type	0.90
neural stem cells	regulates	cell_type	0.90
neural stem cells	activates	cell_type	0.90
H3K9	modulates	compound	0.88
inflammation	promotes	process	0.88
Axonogenesis	modulates	process	0.85
signaling pathways	modulates	pathway	0.85
oocyte maturation	regulates	process	0.85
transcriptional regulation	regulates	process	0.85
8-Cell Embryo Development	expressed_in	process	0.85
Neurogenesis	modulates	process	0.85
Cognitive Impairment	regulates	phenotype	0.85
Kaempferol	targets	compound	0.82
somatic cell nuclear transfer	involved_in	process	0.82
Nf-Κb Pathway	regulates	pathway	0.82
BDNF	represses	gene	0.80
Neurodevelopmental Disorders	therapeutic_target	disease	0.80
Neuropsychiatric Disorders	therapeutic_target	disease	0.80
Neurodegenerative Disorders	therapeutic_target	disease	0.80
cloned embryo development	regulates	process	0.80
memory loss	causes	phenotype	0.80
microglia	activates	cell_type	0.80
neurons	inhibits	cell_type	0.80
unfolded protein response	participates_in	pathway	0.80
cortex	expressed_in	brain_region	0.80
synaptic plasticity	participates_in	pathway	0.80
neural stem cells	promotes	cell_type	0.80
H3K27_acetylation	deacetylates	histone_mark	0.80
acetate	regulates	compound	0.75
Somatic Cell Nuclear Transfer	involved_in	process	0.75
Als	activates	disease	0.75
neurodegeneration	therapeutic_target	disease	0.73
neurodegeneration	activates	disease	0.70
GPX4	treats	gene	0.70

Incoming (351)

Source	Relation	Type	Str
Rgfp966	inhibits	drug	0.95
GS-1	degrades	compound	0.95
GS-1	binds	compound	0.92
SATB2	interacts_with	protein	0.90
MIR34A	downregulates	gene	0.90
h-a9571dbb	targets_gene	hypothesis	0.90
h-0e675a41	targets_gene	hypothesis	0.90
Riboflavin	downregulates	drug	0.88
Kaempferol	targets	compound	0.85
HSV-gB	upregulates	protein	0.85
hypoxia	upregulates	process	0.85
riboflavin	downregulates	compound	0.85
Acetate	interacts_with	compound	0.85
h-a9571dbb	targets	hypothesis	0.80
h-0e675a41	targets	hypothesis	0.80
C-Phycocyanin	downregulates	compound	0.80
acetate	activates	compound	0.80
circadian_rhythm	regulated_by	biological_process	0.80
TAU	treats	protein	0.70
MELATONIN	inhibits	drug	0.70
MELATONIN	activates	drug	0.70
AGING	treats	phenotype	0.70
MACROPHAGE	exacerbates	cell_type	0.70
BDNF	associated_with	gene	0.65
HDAC1	associated_with	gene	0.65
HDAC2	associated_with	gene	0.65
AKT	associated_with	gene	0.65
ABCA1	associated_with	gene	0.65
BDNF	targets	gene	0.65
GALANTAMINE	regulates	drug	0.65
ALZHEIMER	associated_with	gene	0.65
AMYLOID	associated_with	gene	0.65
DEMENTIA	associated_with	gene	0.65
AUTOPHAGY	associated_with	gene	0.65
APOPTOSIS	associated_with	gene	0.65
METASTASIS	regulates	phenotype	0.65
NLRP3 INFLAMMASOME	degrades	pathway	0.65
BDNF	co_mentioned_with	gene	0.60
SIRT6	regulates	gene	0.60
HDAC11	expressed_in	gene	0.60
HDAC2	expressed_in	gene	0.60
SIRT7	regulates	gene	0.60
SIRT5	regulates	gene	0.60
BDNF	regulates	gene	0.60
SIRT1	regulates	gene	0.60
HDAC1	expressed_in	gene	0.60
SIRT2	regulates	gene	0.60
SIRT3	regulates	gene	0.60
HDAC2	activates	gene	0.60
NRF2	inhibits	gene	0.60

Targeting Hypotheses (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Selective HDAC3 Inhibition with Cognitive Enhancement	0.563	neurodegeneration	Epigenetic reprogramming in aging neuron
HDAC3-Selective Inhibition for Clock Reset	0.459	neurodegeneration	Epigenetic clocks and biological aging i

Mentioning Analyses (2)

Scientific analyses that reference this entity

Epigenetic reprogramming in aging neurons

neurodegeneration | 2026-04-04 | 9 hypotheses Top: 0.670

Epigenetic clocks and biological aging in neurodegeneration

neurodegeneration | 2026-04-01 | 6 hypotheses Top: 0.469

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Effect of Electronic Prescribing Compared to Paper-Based (Handwritten) Prescribi [PMID:34433219]	Aluga D, Nnyanzi LA, King N, Okolie EA,	Appl Clin Inform	2021	1
Structurally diverse sesquiterpenoids from the aerial parts of Artemisia annua ( [PMID:32891001]	Qin DP, Li HB, Pang QQ, Huang YX, Pan DB	Bioorg Chem	2020	1
Mycobacterium Abscessus: A Rare Cause of Peri-Ductal Mastitis in Endemic Regions [PMID:32580856]	Shaikh A, Vohra LM	J Coll Physicians Surg Pak	2020	1
The scanning ion conductance microscope for cellular physiology. [PMID:23086993]	Lab MJ, Bhargava A, Wright PT, Gorelik J	Am J Physiol Heart Circ Physio	2013	1
Telomere dysfunction causes sustained inflammation in chronic obstructive pulmon [PMID:21885626]	Amsellem V, Gary-Bobo G, Marcos E, Maitr	Am J Respir Crit Care Med	2011	1
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's diseas [PMID:21102463]	Franke A, McGovern DP, Barrett JC, Wang	Nat Genet	2010	1
Discovery of a Covalent HDAC3 Degrader with Excellent Anti-Inflammatory Activity [PMID:41812251]	["Qin H", "Shi Y", "Liu R", "Wang B", "G	Journal of medicinal chemistry	2026	0
Myeloid HDAC3 deletion protects against traumatic optic injury. [PMID:41851071]	Shahror RA, Morris CA, Cunningham A, Chu	Cell death discovery	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
Metabolomics identifies riboflavin as a therapeutic agent for acute pancreatitis [PMID:41352543]	Shi Y, Peng J	J Nutr Biochem	2026	0
β-Hydroxybutyrate improves glymphatic system function and alleviates cerebral ed [PMID:41535708]	Yu MJ, Xiong RQ, Wu JW, Li YC, Xie JX et	Acta Pharmacol Sin	2026	0
SATB2 Mediates H3K9 Delactylation by Recruiting HDAC3 to Repress LCN2 and Inhibi [PMID:41736683]	Wen T, Yang L, Cai S, Liu Y, Fan J et al	Adv Sci (Weinh)	2026	0
Histone deacetylases: Function in tumor development and therapeutic prospects (R [PMID:41783166]	Lin R, Zhang Y, Li H, Liang F	Oncol Lett	2026	0
Regulatory B Cells at the Crossroads of Epigenetic Control and Immune Homeostasi [PMID:41949720]	Angappulige DH, Ballard DJ, Thomas CJ, X	Clin Rev Allergy Immunol	2026	0
Histone decrotonylation plays a distinct role in HIV latency. [PMID:41961925]	Li X, Li D, Tang Y, Nearing M, Varco-Mer	Sci Adv	2026	0
LncRNA SNHG5 promotes macrophage lipid accumulation and aggravates atheroscleros [PMID:41844502]	Liu X, Wang HH, Lan XY, Sun SY, Xu XD, H	Biochimica et biophysica acta.	2026	0
HOX code-based stratification reveals RUNX1T1-HDAC reprogramming as a targetable [PMID:41912135]	Jiang Y, Cheng S, Zhang CY, Jin X, Li L,	Cancer letters	2026	0
Microglial HDAC3 inhibits the migration of CD8-positive T cell in the developmen [PMID:41888851]	Che N, Zhang Y, Wang B, Wu H, Mao Z, Yua	Cell & bioscience	2026	0
GR/HDAC3 Regulates Npas4 Signaling Pathway and Mediates Cognitive Impairment in [PMID:41837847]	Zhao Z, Song Y, Yu X, Gao Q, Wang B, Sun	FASEB journal : official publi	2026	0
EXPRESS: Identification of Acetylation-Related Molecular Signatures in Knee Oste [PMID:41876476]	Wang J, Xu B, Yoon DE, Xu S, Xia S, Xu J	Molecular pain	2026	0

HDAC3

Understanding Entity Pages

Summary

Wiki Pages (21)

HDAC3 Gene

Neurons — Cell Type Hierarchy

Epigenetic Dysregulation in Neurodegeneration

Epigenetic Dysregulation Comparison -- AD/PD/ALS/FTD/HD

Epigenetic Alterations in Alzheimer's Disease

Epigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor

Retromer Dysfunction in Corticobasal Syndrome

Epigenetic Mechanisms in Alzheimer's Disease

Aging vs Neurodegeneration: Mechanistic Comparison Matrix

epigenetics-neurodegeneration

Epigenetic Changes in PSP

RXRG — Retinoid X Receptor Gamma

ATF3 Protein

Epigenetic Alterations in Alzheimer's Disease

PDLIM7 Epigenetic Activation in Parkinson's Disease

Autophagy Enhancement for Tauopathy

HDAC7 Protein

Dopamine Agonists

RORC Gene

Lactate Lactylation in Neurodegeneration

RORγ Protein