SIRT1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the SIRT1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | SIRT1 |
|---|---|
| Full Name | Sirtuin 1 |
| Gene Type | protein coding |
| Chromosomal Location | 10q21.3 |
| NCBI Gene ID | 23411 ncbi.nlm.nih.gov/gene/23411 |
| Ensembl ID | ENSG00000096717 |
| UniProt ID | Q96EB6 |
| OMIM ID | 604479 |
| HGNC ID | 14929 |
| Aliases | SIR2L1, hSIR2, SIR2, hSIRT1, SIR2alpha |
Description
The SIRT1 gene encodes sirtuin 1, a NAD+-dependent class III histone deacetylase that regulates a wide range of cellular processes including metabolism, stress response, apoptosis, inflammation, and circadian rhythm. It deacetylates both histone and non-histone substrates, such as p53, FOXO, and PGC-1α, thereby influencing gene expression and cellular homeostasis. SIRT1 is implicated in aging, metabolic disorders, cancer, and neurodegeneration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | SIRT1 regulates insulin sensitivity and glucose metabolism via deacetylation of PGC-1α and FOXO; reduced SIRT1 activity is associated with insulin resistance. | Multiple studies, e.g., PMID: 21884946 |
| Alzheimer's Disease | SIRT1 deacetylates tau and APP, reducing amyloid-beta accumulation and tau phosphorylation; overexpression is neuroprotective. | PMID: 20072129 |
| Cancer (various) | SIRT1 can act as a tumor suppressor or oncogene depending on context; it deacetylates p53 and NF-κB, affecting apoptosis and inflammation. | COSMIC and literature, e.g., PMID: 23382044 |
| Cardiovascular Disease | SIRT1 protects against cardiac hypertrophy and ischemia-reperfusion injury via deacetylation of eNOS and FOXO. | PMID: 19520835 |
| Inflammatory Diseases | SIRT1 inhibits NF-κB signaling, reducing pro-inflammatory cytokine production; dysregulation contributes to chronic inflammation. | PMID: 20075857 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.9 | Medium |
| Heart | 6.2 | Low |
| Liver | 10.5 | Medium |
| Kidney | 7.8 | Medium |
| Testis | 12.3 | High |
| Skeletal Muscle | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.8 | Cervical cancer cell line; moderate expression |
| HepG2 | 11.2 | Hepatocellular carcinoma; high expression |
| MCF7 | 7.5 | Breast cancer; moderate expression |
| A549 | 6.9 | Lung carcinoma; moderate expression |
| SH-SY5Y | 8.1 | Neuroblastoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1043C>T (p.Thr348Met) | Missense | 0.01% (gnomAD) | Reduced deacetylase activity; associated with metabolic syndrome |
| c.1484A>G (p.Tyr495Cys) | Missense | 0.005% | Impaired substrate binding; potential loss-of-function |
| c.1397G>A (p.Arg466His) | Missense | 0.002% | Altered catalytic activity; reported in cancer samples |
| c.−196C>T (promoter) | Regulatory | 5% (population) | Affects promoter activity; linked to obesity risk |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish SIRT1 deacetylase activity, leading to increased acetylation of substrates like p53 and FOXO, affecting apoptosis and metabolism.
Gain of Function (GOF)
Rare mutations that enhance SIRT1 activity, potentially promoting cell survival and metabolic efficiency; not well-documented.
Dominant Negative (DN)
Mutations that produce a defective SIRT1 protein that interferes with wild-type function, often by dimerization; not commonly reported.
View complete mutation data：
Gene Ontology (GO)
| • NAD+ binding | • histone deacetylase activity |
| • protein deacetylase activity | • zinc ion binding |
| • transcription coregulator activity | • chromatin binding |
| • protein homodimerization activity |
Pathways
• Longevity regulating pathway
• AMPK signaling pathway
• FoxO signaling pathway
• p53 signaling pathway
• Circadian rhythm
• Metabolic pathways
Protein Summary
SIRT1 is a 747-amino acid protein with a conserved sirtuin core domain that binds NAD+ and catalyzes deacetylation of lysine residues. It localizes predominantly to the nucleus but can shuttle to the cytoplasm. SIRT1 interacts with numerous transcription factors and co-regulators, modulating stress responses, energy metabolism, and inflammation. Its activity is regulated by post-translational modifications, cellular NAD+ levels, and small molecule activators like resveratrol.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIRT1 Knockout HEK293 Cell Line | EDJ-KQ1128 | Human | 23411 | Details Get a Quote |
| SIRT1 Knockout A-549 Cell Line | EDJ-KQ20328 | Human | 23411 | Details Get a Quote |
| SIRT1 Knockout HCT 116 Cell Line | EDJ-KQ20329 | Human | 23411 | Details Get a Quote |
| SIRT1 Knockout HeLa Cell Line | EDJ-KQ20330 | Human | 23411 | Details Get a Quote |
