SIRT2
sirtuin 2, the group of Sirtuins
Basic information
Region (hg38): 19:38878554-38899862
Previous symbols: [ "SIR2L" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (23 variants)
- not provided (7 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIRT2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 23 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 1 | |||||
| Total | 0 | 0 | 23 | 1 | 6 |
Variants in SIRT2
This is a list of pathogenic ClinVar variants found in the SIRT2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-38878729-T-G | Benign (Feb 18, 2020) | |||
| 19-38879190-C-T | not specified | Uncertain significance (Jul 21, 2021) | ||
| 19-38879207-G-A | not specified | Uncertain significance (Dec 26, 2023) | ||
| 19-38879251-C-T | Benign (May 25, 2018) | |||
| 19-38879264-G-C | not specified | Uncertain significance (Sep 29, 2023) | ||
| 19-38879289-G-A | not specified | Uncertain significance (Apr 26, 2023) | ||
| 19-38879295-G-T | Benign (Dec 31, 2019) | |||
| 19-38879484-C-T | not specified | Uncertain significance (Oct 03, 2022) | ||
| 19-38879656-T-A | not specified | Uncertain significance (Mar 07, 2024) | ||
| 19-38879699-C-A | not specified | Uncertain significance (Aug 08, 2022) | ||
| 19-38879701-G-A | not specified | Uncertain significance (Mar 22, 2023) | ||
| 19-38880713-A-G | not specified | Uncertain significance (May 01, 2023) | ||
| 19-38881106-C-T | not specified | Uncertain significance (Jan 17, 2024) | ||
| 19-38881122-C-T | not specified | Uncertain significance (Sep 14, 2022) | ||
| 19-38881125-G-A | not specified | Uncertain significance (Dec 20, 2022) | ||
| 19-38881140-C-T | not specified | Uncertain significance (Feb 16, 2023) | ||
| 19-38881150-C-T | not specified | Uncertain significance (Sep 25, 2023) | ||
| 19-38881153-T-C | not specified | Uncertain significance (Jan 09, 2024) | ||
| 19-38881470-G-A | not specified | Uncertain significance (Jan 26, 2023) | ||
| 19-38883666-C-T | Benign (Dec 31, 2019) | |||
| 19-38883705-C-G | not specified | Uncertain significance (Sep 16, 2021) | ||
| 19-38883729-C-T | not specified | Uncertain significance (Jul 26, 2022) | ||
| 19-38883737-C-T | not specified | Uncertain significance (Oct 22, 2021) | ||
| 19-38889130-C-T | Benign (Dec 31, 2019) | |||
| 19-38889702-G-A | not specified | Uncertain significance (Aug 08, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SIRT2 | protein_coding | protein_coding | ENST00000249396 | 16 | 21306 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.33e-8 | 0.895 | 125714 | 0 | 34 | 125748 | 0.000135 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.700 | 208 | 238 | 0.872 | 0.0000144 | 2518 |
| Missense in Polyphen | 71 | 86.393 | 0.82182 | 890 | ||
| Synonymous | 0.968 | 85 | 97.1 | 0.875 | 0.00000650 | 745 |
| Loss of Function | 1.73 | 16 | 25.4 | 0.630 | 0.00000117 | 301 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000640 | 0.000607 |
| Ashkenazi Jewish | 0.000198 | 0.000198 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000792 | 0.0000791 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000515 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:24177535, PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20587414, PubMed:21081649, PubMed:20543840, PubMed:22014574, PubMed:21726808, PubMed:21949390, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24940000, PubMed:24769394, PubMed:24681946). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed:23468428). Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection (PubMed:23908241). During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed:24940000). Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1- mediated autophagy (PubMed:20543840). Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia (PubMed:24681946). Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed:18249187). Deacetylates also EIF5A (PubMed:22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor (PubMed:22014574). {ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:16909107, ECO:0000269|PubMed:17488717, ECO:0000269|PubMed:17574768, ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:18249187, ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:18640115, ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:18995842, ECO:0000269|PubMed:19282667, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:20587414, ECO:0000269|PubMed:21081649, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:22771473, ECO:0000269|PubMed:22819792, ECO:0000269|PubMed:23468428, ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:24177535, ECO:0000269|PubMed:24681946, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:24940000}.; FUNCTION: Isoform 2: Deacetylates EP300, alpha-tubulin and histone H3 and H4. {ECO:0000269|PubMed:24177535}.;
- Pathway
- NAD+ metabolism;NAD+ biosynthetic pathways;Signaling events mediated by HDAC Class III
(Consensus)
Recessive Scores
- pRec
- 0.337
Intolerance Scores
- loftool
- 0.949
- rvis_EVS
- 0.02
- rvis_percentile_EVS
- 55.61
Haploinsufficiency Scores
- pHI
- 0.311
- hipred
- Y
- hipred_score
- 0.532
- ghis
- 0.499
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sirt2
- Phenotype
- skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- sirt2
- Affected structure
- intersegmental vessel
- Phenotype tag
- abnormal
- Phenotype quality
- increased branchiness
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;chromatin silencing at rDNA;chromatin silencing;chromatin silencing at telomere;protein ADP-ribosylation;protein deacetylation;autophagy;regulation of exit from mitosis;negative regulation of cell population proliferation;negative regulation of autophagy;negative regulation of peptidyl-threonine phosphorylation;phosphatidylinositol 3-kinase signaling;gene silencing;histone deacetylation;substantia nigra development;myelination in peripheral nervous system;regulation of myelination;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;cellular response to oxidative stress;peptidyl-lysine deacetylation;cellular response to hepatocyte growth factor stimulus;negative regulation of protein catabolic process;regulation of phosphorylation;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of DNA binding;protein kinase B signaling;cellular lipid catabolic process;innate immune response;negative regulation of fat cell differentiation;positive regulation of meiotic nuclear division;negative regulation of striated muscle tissue development;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;hepatocyte growth factor receptor signaling pathway;cell division;meiotic cell cycle;regulation of cell cycle;response to redox state;positive regulation of cell division;positive regulation of attachment of spindle microtubules to kinetochore;negative regulation of transcription from RNA polymerase II promoter in response to hypoxia;cellular response to caloric restriction;negative regulation of oligodendrocyte progenitor proliferation;histone H3 deacetylation;histone H4 deacetylation;cellular response to molecule of bacterial origin;cellular response to hypoxia;cellular response to epinephrine stimulus;tubulin deacetylation;positive regulation of execution phase of apoptosis;positive regulation of oocyte maturation;negative regulation of NLRP3 inflammasome complex assembly;negative regulation of defense response to bacterium;negative regulation of reactive oxygen species metabolic process;positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia
- Cellular component
- chromosome, telomeric region;nucleus;chromatin silencing complex;chromosome;nuclear heterochromatin;nucleolus;cytoplasm;mitochondrion;centrosome;centriole;spindle;cytosol;microtubule;plasma membrane;growth cone;midbody;paranodal junction;paranode region of axon;perikaryon;myelin sheath;lateral loop;Schmidt-Lanterman incisure;juxtaparanode region of axon;perinuclear region of cytoplasm;mitotic spindle;meiotic spindle;glial cell projection
- Molecular function
- chromatin binding;NAD+ ADP-ribosyltransferase activity;histone deacetylase activity;protein binding;transcription factor binding;zinc ion binding;NAD-dependent histone deacetylase activity;protein deacetylase activity;NAD-dependent protein deacetylase activity;histone acetyltransferase binding;histone deacetylase binding;tubulin deacetylase activity;ubiquitin binding;NAD-dependent histone deacetylase activity (H4-K16 specific);NAD+ binding