SIRT1

Chr 10

sirtuin 1

Also known as: SIR2, SIR2L1, SIR2alpha

NCBI Gene: 23411ENSG00000096717UniProt: Q96EB6

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

GeneReviewsResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)
monogenic diabetes · ADLimitednot for standalone diagnostic reporting
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
9
Active trials
3153
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.50
LOEUF
DN
Mechanism· predicted
📖
GeneReview available — SIRT1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.50LOEUF
pLI 0.087
Z-score 3.47
OE 0.27 (0.15–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.79Z-score
OE missense 0.72 (0.65–0.81)
243 obs / 335.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.27 (0.15–0.50)
0≤0.351.4
Missense OE?0.72 (0.65–0.81)
0≤0.61.4
Synonymous OE?1.12
0≤1.21.6
LoF obs/exp: 7 / 26.1Missense obs/exp: 243 / 335.5Syn Z: -0.98

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SIRT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rheumatoid ArthritisOsteoarthritisSarcopenia

Effect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study

NOT YET RECRUITING
NCT06480643Phase NAAmsterdam UMC, location VUmcStarted 2024-12-01
High load exercise typeLow load exercise type
Aging

Sex-Speciffic Longevity Food Supplements

ACTIVE NOT RECRUITING
NCT07404449Phase PHASE1University of PrimorskaStarted 2026-03-07
compound food supplements - female specificcompound food supplements - male specificPlacebo
Anthracycline Related Cardiotoxicity in Breast Cancer

Protective Effects of the Nutritional Supplement Sulforaphane on Doxorubicin-Associated Cardiac Dysfunction

RECRUITING
NCT03934905Phase PHASE1, PHASE2Texas Tech University Health Sciences CenterStarted 2022-06-01
sulforaphanePlacebo Oral Tablet
Kidney Disease, ChronicKidney Failure Chronic

Physical Exercise and Biomolecular Analysis to Reduce Uremic Toxins in Chronic Kidney Disease: An Exploratory Study

ENROLLING BY INVITATION
NCT06910475Phase NACatholic University of BrasíliaStarted 2025-04-01
Resistance trainingEndurance trainingConcurrent training
Aging

Morning-Evening Specific Longevity Food Supplement

ACTIVE NOT RECRUITING
NCT07416396Phase PHASE1University of PrimorskaStarted 2026-03-07
Morning- and evening-specific compound food supplementControl
Obesity & Overweight

Supplementation With Sirtuin Activators in Women With Increased Body Weight

RECRUITING
NCT07245979Phase NAPoznan University of Life SciencesStarted 2025-10-08
Sirtuin activatorsPlacebo
Aging

Evaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging

ACTIVE NOT RECRUITING
NCT07114536Phase NAShenzhen Hygieia Biotech Co., LtdStarted 2025-08-20
Calcium-a-ketoglutaratePlacebo(starch)
Multiple Myeloma (MM)

Moving Forward With Myeloma: A Lifestyle Intervention for Individuals With Multiple Myeloma

RECRUITING
NCT07236502Phase NAMedical College of WisconsinStarted 2026-01-30
Immediate interventionWaitlist
ObesityType2diabetesLipodystrophy

Susceptibility to Infectious Diseases in obEsity: an endocRine trAnslational socioLogic Evaluation, "SIDERALE"

RECRUITING
NCT06236932Phase NAFederico II UniversityStarted 2023-12-29
Mediterranean dietMelatonin supplementation

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients