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.

1065Connections

5Hypotheses

3Analyses

50Outgoing

50Incoming

9Experiments

3Debates

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
Known Drugs/Compounds	acetate, Acetate, GS-1, H3K9, Kaempferol, MELATONIN
Interactions	ABCA1, AGING, AKT, ALZHEIMER, ALZHEIMER'S DISEASE, AMPA RECEPTOR
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	Selective HDAC3 Inhibition with Cognitive Enhancem HDAC3-Selective Inhibition for Clock Reset HDAC3-Dependent A1 Astrocyte Commitment Window
KG Connections	1064 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — HDAC3 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

4A69 — X-ray / Cryo-EM

🔮 AI Predicted Structure

O15379 — 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

HDAC3 Gene

gene · 960 words

→

HDAC3 Protein

protein · 788 words

→

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 (727)

Target	Relation	Type	Str
HDAC3	encodes	protein	0.00
Brain Development	regulates	process	0.95
endothelial cell metabolic reprogramming	drives	process	0.95
Nlrp3 Inflammasome	promotes	process	0.95
Neurodegeneration	regulates	process	0.95
Alzheimer'S Disease	associated_with	disease	0.95
neural stem cells	regulates	cell_type	0.90
neural stem cells	activates	cell_type	0.90
diabetic retinopathy	involved_in	disease	0.90
Memory Formation	regulates	process	0.90
histone acetylation	suppresses	process	0.90
tumorigenesis	promotes	process	0.90
mitochondrial fission	promotes	process	0.90
NLRP3	associated_with	protein	0.90
Nrf2 Signaling Pathway	mediates	pathway	0.90
NRF2	regulates	gene	0.90
Pro-Inflammatory Cytokines	regulates	protein	0.90
Tumor Progression	involved_in	process	0.90
neural stem cells	inhibits	cell_type	0.90
epigenetic regulation	participates_in	pathway	0.90
H3K9	modulates	compound	0.88
inflammation	promotes	process	0.88
Axonogenesis	modulates	process	0.85
Neurogenesis	modulates	process	0.85
8-Cell Embryo Development	expressed_in	process	0.85
Cognitive Impairment	regulates	phenotype	0.85
transcriptional regulation	regulates	process	0.85
oocyte maturation	regulates	process	0.85
signaling pathways	modulates	pathway	0.85
somatic cell nuclear transfer	involved_in	process	0.82
Nf-Κb Pathway	regulates	pathway	0.82
Kaempferol	targets	compound	0.82
synaptic plasticity	participates_in	pathway	0.80
NLRP3 inflammasome	activates	pathway	0.80
cortex	expressed_in	brain_region	0.80
unfolded protein response	participates_in	pathway	0.80
microglia	activates	cell_type	0.80
neurons	inhibits	cell_type	0.80
neural stem cells	associated_with	cell_type	0.80
BDNF	represses	gene	0.80
cloned embryo development	regulates	process	0.80
Neuropsychiatric Disorders	therapeutic_target	disease	0.80
Neurodevelopmental Disorders	therapeutic_target	disease	0.80
memory loss	causes	phenotype	0.80
Neurodegenerative Disorders	therapeutic_target	disease	0.80
H3K27_acetylation	deacetylates	histone_mark	0.80
acetate	regulates	compound	0.75
Als	activates	disease	0.75
Somatic Cell Nuclear Transfer	involved_in	process	0.75
neurodegeneration	therapeutic_target	disease	0.73

Incoming (338)

Source	Relation	Type	Str
HDAC3	encodes	gene	0.00
Rgfp966	inhibits	drug	0.95
GS-1	degrades	compound	0.95
GS-1	binds	compound	0.92
h-0e675a41	targets	hypothesis	0.90
h-a9571dbb	targets	hypothesis	0.90
MIR34A	downregulates	gene	0.90
SATB2	interacts_with	protein	0.90
Riboflavin	downregulates	drug	0.88
riboflavin	downregulates	compound	0.85
Acetate	interacts_with	compound	0.85
hypoxia	upregulates	process	0.85
HSV-gB	upregulates	protein	0.85
Kaempferol	targets	compound	0.85
acetate	activates	compound	0.80
GABA	inhibits	gene	0.80
C-Phycocyanin	downregulates	compound	0.80
GS-1	targets	gene	0.80
circadian_rhythm	regulated_by	process	0.80
MELATONIN	activates	drug	0.70
NLRP3	interacts_with	gene	0.70
AGING	treats	phenotype	0.70
MELATONIN	inhibits	drug	0.70
TAU	treats	protein	0.70
MACROPHAGE	exacerbates	cell_type	0.70
BDNF	associated_with	gene	0.65
ALZHEIMER	associated_with	gene	0.65
APOPTOSIS	associated_with	gene	0.65
AKT	associated_with	gene	0.65
DEMENTIA	associated_with	gene	0.65
BDNF	targets	gene	0.65
HDAC2	associated_with	gene	0.65
AMYLOID	associated_with	gene	0.65
ABCA1	associated_with	gene	0.65
HDAC1	associated_with	gene	0.65
AUTOPHAGY	associated_with	gene	0.65
NLRP3 INFLAMMASOME	degrades	pathway	0.65
GALANTAMINE	regulates	drug	0.65
METASTASIS	regulates	phenotype	0.65
INFLAMMATION	inhibits	gene	0.60
APOPTOSIS	inhibits	gene	0.60
BCL-2	inhibits	gene	0.60
NF-ΚB	inhibits	gene	0.60
SRC	activates	gene	0.60
AGING	activates	gene	0.60
MITOPHAGY	activates	gene	0.60
HDAC	activates	gene	0.60
CYTOKINES	activates	gene	0.60
STAT3	activates	gene	0.60
NRF2	protects_against	gene	0.60

Targeting Hypotheses (5)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Selective HDAC3 Inhibition with Cognitive Enhancement	0.779	neurodegeneration	Epigenetic reprogramming in aging neuron
HDAC3-Selective Inhibition for Clock Reset	0.710	neurodegeneration	Epigenetic clocks and biological aging i
Butyrate-Producing Commensal Depletion Creates Vicious Cycle	0.630	neurodegeneration	How does gut microbiome dysbiosis contri
CX3CR1-Targeted HDAC3 Knockdown in Microglia via AAV9 Delive	0.620	pharmacology	How can CNS-selective HDAC/DNMT inhibito
HDAC3-Dependent A1 Astrocyte Commitment Window	0.611	neurodegeneration	What is the optimal therapeutic window d

Mentioning Analyses (3)

Scientific analyses that reference this entity

Experiments (9)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Epigenetic clocks association with brain aging patterns in older women	exploratory	cognitive impairment and demen	0.900	0.00	human patients	proposed	N/A
Proposed experiment from debate on Epigenetic clocks and biological ag	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
Mechanism: Why Does Amyloid Removal Only Slow Decline 27%?	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Animal Model Comparison for Neurodegenerative Disease Therapeutics	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,100,000
Epigenetic Dysregulation in Huntington's Disease — Therapeutic Targeti	validation	Neurodegeneration	0.400	0.50	human	completed	$3,000,000
Epigenetic Dysregulation Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,500,000
Epigenetic Regulation Dysfunction in Alzheimer's and Parkinson's Disea	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Proposed experiment from debate on Microglia activate astrocytes via I	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$100,000
CRISPR Gene Correction Approaches for CBS/PSP	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000

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
HDAC3 Preserves the primordial follicle reserve by epigenetically suppressing fe [PMID:41803516]	["Chen Z", "Guo J", "Gao M", "Wang H", "	Cellular and molecular life sc	2026	0
Determination of the effects of [PMID:41823023]	["Yir\u00fcn A", "\u00c7ak\u0131r D", "E	Journal of Alzheimer's disease	2026	0
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
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
Histone Deacetylases Are Required for Aedes aegypti Female Reproduction and Embr [PMID:41764745]	["Balasubramani S", "Palli S"]	Archives of insect biochemistr	2026	0
Microglial HDAC3 inhibits the migration of CD8-positive T cell in the developmen [PMID:41888851]	Na Che; Yang Zhang; Bo Wang; Hongxing Wu	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

Debates (3)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning HDAC3 in their description or question text

No additional research found