gene

SIRT6

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about SIRT6: 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.

440Connections

1Hypotheses

2Analyses

50Outgoing

50Incoming

Summary

SIRT6 is a gene implicated in neurodegeneration research. Key relationships include: regulates, activates, expressed in. Associated with ALS, Aging, Als. Connected to 213 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	SIRT6
Chromosome	19p13.3<br>
Protein Type	Epigenetic Regulator
Target Class	Epigenetic Regulator
Function	SIRT6 exhibits multiple enzymatic activities
Mechanism of Action	Small molecule activation or inhibition of NAD+-dependent deacetylase activity
Primary Expression	most tissues: - Brain: cortex, hippocampus, cerebellum - Substantia nigra - Low expression but
Druggability	Low (0.41)
Clinical Stage	Phase I
Molecular Weight	36 kDa
Pathways	NF-κB
UniProt ID	Q9Y5W5
NCBI Gene ID	51588
Ensembl ID	ENSG00000173120
GeneCards	SIRT6
Human Protein Atlas	SIRT6
Associated Diseases	AGING, ALS, AMYOTROPHIC LATERAL SCLEROSIS, Alzheimer
Known Drugs/Compounds	Withaferin A, nicotinamide, rapamycin
Interactions	EGR2, PARP1, CD38, HNRNPA2B1, NAMPT, CD36
SciDEX Target	View Target Profile (1 clinical trials)
SciDEX Hypotheses	SIRT6-NAD+ Axis Enhancement Therapy
KG Connections	433 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure: SIRT6 — PDB 3K35 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
    SIRT6["SIRT6"]
    SIRT6 -->|"expressed in"| rgcs["rgcs"]
    SIRT6 -.protects against.-> optic_nerve["optic_nerve"]
    SIRT6 -->|"inhibits"| Cancer["Cancer"]
    SIRT6 -->|"inhibits"| Als["Als"]
    SIRT6 -->|"inhibits"| Tumor["Tumor"]
    SIRT6 -->|"inhibits"| Inflammation["Inflammation"]
    SIRT6 -->|"regulates"| Ms["Ms"]
    SIRT6 -->|"regulates"| Diabetes["Diabetes"]
    h_50a535f9["h-50a535f9"] -->|"target for"| SIRT6
    NAMPT["NAMPT"] -->|"inhibits"| SIRT6
    CD36["CD36"] -->|"activates"| SIRT6
    CD38["CD38"] -->|"inhibits"| SIRT6
    PARP1["PARP1"] -->|"inhibits"| SIRT6
    HNRNPA2B1["HNRNPA2B1"] -->|"inhibits"| SIRT6
    BDNF["BDNF"] -->|"regulates"| SIRT6
    HDAC3["HDAC3"] -->|"regulates"| SIRT6
    HDAC11["HDAC11"] -->|"regulates"| SIRT6

Outgoing (288)

Target	Relation	Type	Str
Macrophage Efferocytosis	regulates	process	0.95
Retinal Ganglion Cell Degeneration	protects_against	process	0.95
Optic Nerve Degeneration	protects_against	process	0.95
Retinal Ganglion Cell	expressed_in	cell_type	0.95
miR-216a-5p-216b-5p-217 Cluster	inhibits	biomarker	0.92
Retinal Ganglion Cell Senescence	inhibits	process	0.90
Epigenetics	involved_in	mechanism	0.90
Retinal Ganglion Cells	expressed_in	cell_type	0.90
Diabetic Periodontitis	protects_against	disease	0.90
retinal ganglion cells	protects_against	cell_type	0.90
Diabetic Periodontitis	associated_with	disease	0.85
Inflammation Resolution	modulates	process	0.85
MIR-216A-5P	inhibits	gene	0.85
MIR-217	inhibits	gene	0.85
macrophage efferocytosis	inhibits	process	0.85
Mitochondrial Dysfunction	inhibits	process	0.85
Inflammation Resolution	regulates	biological_process	0.80
NAD metabolism	involved_in	pathway	0.80
Macrophage	regulates	cell_type	0.80
mitochondrial dysfunction	prevents	process	0.80
SIRT3	activates	gene	0.80
SIRT1	activates	gene	0.80
NAD+_pathway	requires	metabolic_pathway	0.80
Inflammation	regulates	disease	0.75
Senescence	activates	disease	0.75
Als	associated_with	disease	0.75
Aging	associated_with	disease	0.75
SIRT7	expressed_in	gene	0.70
SIRT5	expressed_in	gene	0.70
SIRT1	expressed_in	gene	0.70
SIRT3	expressed_in	gene	0.70
SIRT2	expressed_in	gene	0.70
ATG10	inhibits	gene	0.70
AUTOPHAGY	regulates	gene	0.70
Autophagy	regulates	pathway	0.70
APOPTOSIS	regulates	gene	0.70
Apoptosis	regulates	pathway	0.70
ENDOTHELIAL CELLS	activates	cell_type	0.70
SENESCENCE	exacerbates	phenotype	0.70
LIPID METABOLISM	regulates	phenotype	0.70
DNA DAMAGE RESPONSE	interacts_with	pathway	0.70
SENESCENCE	protects_against	phenotype	0.70
NEUROINFLAMMATION	stabilizes	phenotype	0.70
AMYOTROPHIC LATERAL SCLEROSIS	causes	disease	0.70
STROKE	activates	disease	0.70
STROKE	inhibits	disease	0.70
NAD+ metabolism	participates_in	pathway	0.65
Cancer	inhibits	disease	0.65
Als	inhibits	disease	0.65
Tumor	inhibits	disease	0.65

Incoming (152)

Source	Relation	Type	Str
h-50a535f9	targets_gene	hypothesis	0.90
h-50a535f9	targets	hypothesis	0.80
high glucose	downregulates	phenotype	0.80
Withaferin A	modulates	compound	0.75
SIRT4	expressed_in	gene	0.70
CD38	reduces	gene	0.65
PARP1	reduces	gene	0.65
MACROPHAGE	causes	cell_type	0.65
NAD	activates	gene	0.65
NAMPT	inhibits	gene	0.60
CD36	activates	gene	0.60
CD38	inhibits	gene	0.60
EGR2	associated_with	gene	0.60
PARP1	inhibits	gene	0.60
HNRNPA2B1	inhibits	gene	0.60
BDNF	regulates	gene	0.60
HDAC3	regulates	gene	0.60
HDAC11	regulates	gene	0.60
SIRT5	expressed_in	gene	0.60
HDAC7	regulates	gene	0.60
SIRT7	expressed_in	gene	0.60
HDAC6	regulates	gene	0.60
SIRT2	associated_with	gene	0.60
SIRT1	expressed_in	gene	0.60
HDAC1	regulates	gene	0.60
HDAC2	regulates	gene	0.60
EGR2	inhibits	gene	0.60
TAU	regulates	gene	0.60
SIRT3	expressed_in	gene	0.60
CD38	activates	entity	0.60
NAMPT	activates	entity	0.60
PARP1	activates	entity	0.60
CD36	causes	gene	0.60
HNRNPA2B1	associated_with	gene	0.60
glycolysis	regulates	pathway	0.60
CDK2	interacts_with	gene	0.60
SIRT7	interacts_with	gene	0.60
MTOR	interacts_with	gene	0.60
SIRT3	inhibits	gene	0.60
SIRT4	inhibits	gene	0.60
SIRT3	protects_against	gene	0.60
SIRT4	protects_against	gene	0.60
AGING	associated_with	gene	0.60
MITOCHONDRIAL DYSFUNCTION	activates	gene	0.60
AGING	expressed_in	gene	0.60
NAD	inhibits	gene	0.60
MACROPHAGE	activates	cell_type	0.60
MACROPHAGES	activates	cell_type	0.60
MONOCYTE	activates	cell_type	0.60
MONOCYTES	activates	cell_type	0.60

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
SIRT6-NAD+ Axis Enhancement Therapy	0.395	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 (18)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
SIRT6-regulated macrophage efferocytosis epigenetically controls inflammation re [PMID:36593966]	Li B, Xin Z, Gao S, Li Y, Guo S, Fu Y, X	Theranostics	2023	1
Assessing the Status of Mandatory Tuberculosis Case Notification among Private P [PMID:35068738]	Duggal K, Elsy M, Majella MG, Akkilagunt	Indian J Community Med	2021	1
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic [PMID:33888596]	Yoshino M, Yoshino J, Kayser BD, Patti G	Science	2021	1
Protocol for the Bottom-Up Proteomic Analysis of Mouse Spleen. [PMID:33377090]	Dowling P, Gargan S, Zweyer M, Henry M,	STAR Protoc	2020	1
Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity [PMID:30193097]	Latorre-Muro P, Baeza J, Armstrong EA, H	Mol Cell	2018	1
The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcin [PMID:28329682]	Nargund AM, Pham CG, Dong Y, Wang PI, Os	Cell Rep	2017	1
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype [PMID:26686024]	Wiley CD, Velarde MC, Lecot P, Liu S, Sa	Cell Metab	2016	1
SIRT6 inhibits intermittent hypoxia-induced lung injury by stabilizing NRF2. [PMID:41478020]	Qin R, Liu Z, Li R, Li Y, Yang Y et al.	Tissue Cell	2026	0
Inflammation-targeted single-atom nanozymes drive microglial depolarization and [PMID:41624511]	Liu B, Xiang C, Zhang X, Guo W, Wu H et	Mater Today Bio	2026	0
Bupleurum chinense ameliorates metabolic-associated fatty liver disease by modul [PMID:41666508]	Liu S, Chen P, Li Y, Pan Z, Zhang C et a	Phytomedicine	2026	0
Deciphering the role of SIRT6 in suppressing the AMPK-mTOR-TFEB axis: regulation [PMID:41957523]	Li CS, Jin H, Meng R, Baek SW, Kim SH et	Cancer Gene Ther	2026	0
SIRT6 promotes intrahepatic cholangiocarcinoma development by reprogramming glut [PMID:41136182]	Zhang M, Chen C, Zhang H, Long T, Wang T	Gut	2025	0
SGK1-Mediated Vascular Smooth Muscle Cell Phenotypic Transformation Promotes Tho [PMID:39633576]	Leng S, Li H, Zhang P, Dang Z, Shao B, X	Arteriosclerosis, thrombosis,	2025	0
On the interface of aging, cancer, and neurodegeneration with SIRT6 and L1 retro [PMID:39251041]	Nahálková J	Ageing research reviews	2024	0
Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis [PMID:37550003]	Collins JA, Kim CJ, Coleman A, Little A,	Annals of the rheumatic diseas	2023	0
Understanding the Role of Histone Deacetylase and their Inhibitors in Neurodegen [PMID:34151764]	Kumar V, Kundu S, Singh A, Singh S	Current neuropharmacology	2022	0
Ergothioneine and its prospects as an anti-ageing compound. [PMID:36244584]	Apparoo Y, Phan CW, Kuppusamy UR, Sabara	Experimental gerontology	2022	0
Cyclosporine modulates neutrophil functions via the SIRT6-HIF-1α-glycolysis axis [PMID:33634990]	Lu H, Lin J, Xu C, Sun M, Zuo K, Zhang X	Clinical and translational med	2021	0

SIRT6

Understanding Entity Pages

Summary

Wiki Pages (21)

SIRT6 Gene

Therapeutics

Cellular Senescence in Neurodegeneration

cynata-therapeutics

dna-damage-repair

Sirtuin Signaling in Parkinson's Disease

Iduna Therapeutics

Section 103: Sirtuin Pathway and NAD+-Dependent Deacetylases in CBS/PSP

Nicotinamide Riboside

NAD+ Metabolism in Neurodegeneration

Energy Metabolism in Neurodegeneration

Muna Therapeutics

DNA Damage Response in Corticobasal Syndrome

Sirtuin Signaling Pathway

Spin Therapeutics

Anti-Tau Therapeutics

NMNAT1 Gene

Alzheimer's Digital Therapeutics Companies

Amyl Therapeutics

NAD Signaling in Neurodegeneration

AD RNA-Based Therapeutics Companies