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.

479Connections

1Hypotheses

3Analyses

50Outgoing

50Incoming

2Experiments

3Debates

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, Alzheimer
Known Drugs/Compounds	nicotinamide, rapamycin, Withaferin A
Interactions	AKT, AMPK, AND, App, APP, ATG10
SciDEX Target	View Target Profile (1 clinical trials)
SciDEX Hypotheses	SIRT6-NAD+ Axis Enhancement Therapy
KG Connections	472 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — SIRT6 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

3K35 — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q9Y5W5 — AlphaFold

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

Wiki Pages (4)

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 (294)

Target	Relation	Type	Str
benchmark_ot_ad_answer_key:SIRT6	data_in	dataset_row	0.00
Retinal Ganglion Cell Degeneration	protects_against	process	0.95
Macrophage Efferocytosis	regulates	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
Diabetic Periodontitis	protects_against	disease	0.90
Epigenetics	involved_in	mechanism	0.90
Retinal Ganglion Cells	expressed_in	cell_type	0.90
retinal ganglion cells	protects_against	cell_type	0.90
macrophage efferocytosis	inhibits	process	0.85
MIR-217	inhibits	gene	0.85
MIR-216A-5P	inhibits	gene	0.85
Mitochondrial Dysfunction	inhibits	process	0.85
Diabetic Periodontitis	associated_with	disease	0.85
Inflammation Resolution	modulates	process	0.85
Macrophage	regulates	cell_type	0.80
NAD metabolism	involved_in	pathway	0.80
mitochondrial dysfunction	prevents	process	0.80
Inflammation Resolution	regulates	biological_process	0.80
SIRT1	activates	gene	0.80
SIRT3	activates	gene	0.80
NAD+_pathway	requires	metabolic_pathway	0.80
Inflammation	regulates	disease	0.75
Als	associated_with	disease	0.75
Aging	associated_with	disease	0.75
Senescence	activates	disease	0.75
optic_nerve	protects_against	brain_region	0.72
rgcs	expressed_in	cell_type	0.72
rgcs	protects_against	cell_type	0.72
AUTOPHAGY	regulates	gene	0.70
SIRT2	expressed_in	gene	0.70
ATG10	inhibits	gene	0.70
SIRT7	expressed_in	gene	0.70
SIRT3	expressed_in	gene	0.70
Autophagy	regulates	pathway	0.70
SIRT1	expressed_in	gene	0.70
SIRT5	expressed_in	gene	0.70
ENDOTHELIAL CELLS	activates	cell_type	0.70
APOPTOSIS	regulates	gene	0.70
Apoptosis	regulates	pathway	0.70
STROKE	inhibits	disease	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
SENESCENCE	exacerbates	phenotype	0.70

Incoming (185)

Source	Relation	Type	Str
benchmark_ot_ad_answer_key:SIRT6	data_in	dataset_row	0.00
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
MACROPHAGE	causes	cell_type	0.65
NAD	activates	gene	0.65
PARP1	reduces	gene	0.65
CD38	reduces	gene	0.65
SIRT3	expressed_in	gene	0.60
EGR2	inhibits	gene	0.60
TAU	regulates	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
GLAUCOMA	associated_with	entity	0.60
GLAUCOMA	upregulates	entity	0.60
GLAUCOMA	activates	entity	0.60
HDAC	regulates	gene	0.60
OXIDATIVE STRESS	regulates	gene	0.60
CD36	causes	gene	0.60
glycolysis	regulates	pathway	0.60
CDK2	interacts_with	gene	0.60
SIRT7	interacts_with	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
NAMPT	inhibits	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
CD38	activates	entity	0.60
NAMPT	activates	entity	0.60

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
SIRT6-NAD+ Axis Enhancement Therapy	0.667	neurodegeneration	Epigenetic clocks and biological aging i

Mentioning Analyses (3)

Scientific analyses that reference this entity

Experiments (2)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Sirtuin Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Sirtuin Pathway Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000

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
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	Curr Neuropharmacol	2022	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

Debates (3)

Multi-agent debates referencing this entity

SIRT6

Understanding Entity Pages

Summary

Wiki Pages (4)

SIRT6 Gene

SPAM1-SIRT6 Positive Allosteric Modulator in Neurodegeneration

SPAM1: SIRT6 Positive Allosteric Modulator

SIRT6 Protein