SIRT6 Gene: Structure, Function, and Disease Associations
A comprehensive overview of the SIRT6 gene, including its genomic context, protein function, expression patterns, and clinical significance.
Gene Information Card
| Symbol | SIRT6 |
|---|---|
| Full Name | Sirtuin 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.3 |
| NCBI Gene ID | 51548 ncbi.nlm.nih.gov/gene/51548 |
| Ensembl ID | ENSG00000099377 |
| UniProt ID | Q8N6T7 |
| OMIM ID | 606211 |
| HGNC ID | 14934 |
| Aliases | SIR2L6 |
Description
SIRT6 is a member of the sirtuin family of NAD+-dependent deacetylases and ADP-ribosyltransferases. It is localized to the nucleus and plays critical roles in DNA repair, telomere maintenance, genomic stability, and metabolic regulation. SIRT6 is involved in chromatin remodeling and has been implicated in aging, cancer, and metabolic diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | SIRT6 acts as a tumor suppressor by promoting DNA repair and maintaining genomic stability. Loss of SIRT6 leads to increased genomic instability and oncogene activation. | COSMIC; multiple studies (e.g., Kugel et al., 2016) |
| Metabolic syndrome | SIRT6 regulates glucose and lipid metabolism via deacetylation of histones and transcription factors, influencing insulin sensitivity and fat accumulation. | OMIM; studies in mouse models (e.g., Zhong et al., 2010) |
| Aging and longevity | SIRT6 is associated with lifespan regulation and age-related diseases, including cardiovascular and neurodegenerative conditions. | OMIM; studies in transgenic mice (e.g., Kanfi et al., 2012) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Heart | 8.5 | Medium |
| Liver | 7.8 | Medium |
| Kidney | 9.1 | Medium |
| Testis | 12.3 | High |
| Skeletal Muscle | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| HepG2 | 12.8 | High expression |
| MCF7 | 10.5 | Medium expression |
| A549 | 9.7 | Medium expression |
| K562 | 8.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.18C>T (p.Gly6=) | Synonymous | 0.001% (gnomAD) | No known effect |
| c.123G>A (p.Met41Ile) | Missense | 0.002% (gnomAD) | Potential impact on protein stability |
| c.456C>T (p.Thr152=) | Synonymous | 0.005% (gnomAD) | No known effect |
| c.789A>G (p.Leu263=) | Synonymous | 0.001% (gnomAD) | No known effect |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SIRT6 are rare but have been associated with increased genomic instability and cancer susceptibility. Experimental knockdown of SIRT6 leads to impaired DNA repair and metabolic dysregulation.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented in SIRT6. Overexpression of SIRT6 has been shown to extend lifespan in animal models, suggesting potential beneficial effects.
Dominant Negative (DN)
No dominant-negative mutations have been reported for SIRT6 in the literature.
View complete mutation data：
Gene Ontology (GO)
| • NAD+ ADP-ribosyltransferase activity | • Protein deacetylase activity |
| • Chromatin binding | • DNA repair |
| • Telomere maintenance | • Cellular response to DNA damage stimulus |
| • Regulation of transcription by RNA polymerase II | • Metabolic process |
Pathways
• DNA Repair Pathways (e.g.
• Base Excision Repair
• Homologous Recombination)
• Telomere Maintenance
• Metabolic Regulation (e.g.
• Glycolysis
• Gluconeogenesis)
• Longevity Regulation Pathway
Protein Summary
SIRT6 is a nuclear protein that functions as a NAD+-dependent deacetylase and ADP-ribosyltransferase. It deacetylates histone H3 at lysine 9 (H3K9) and lysine 56 (H3K56), thereby regulating chromatin structure and gene expression. SIRT6 is essential for DNA double-strand break repair, telomere stability, and metabolic homeostasis. It also modulates NF-κB signaling and has been implicated in inflammation and aging. SIRT6 expression is relatively ubiquitous, with higher levels in tissues with high metabolic activity. Its role as a tumor suppressor and longevity factor makes it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SIRT6 Knockout HEK293 Cell Line | EDJ-KQ948 | Human | 51548 | Details Get a Quote |
| SIRT6 Knockout A-549 Cell Line | EDJ-KQ19936 | Human | 51548 | Details Get a Quote |
| SIRT6 Knockout HeLa Cell Line | EDJ-KQ19937 | Human | 51548 | Details Get a Quote |
| SIRT6 Knockout HCT 116 Cell Line | EDJ-KQ18608 | Human | 51548 | Details Get a Quote |
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