SIRT3
Basic information
Region (hg38): 11:215030-236931
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIRT3 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 | 5 | |||||
missense | 33 | 38 | ||||
nonsense | 0 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 0 | |||||
non coding | 1 | |||||
Total | 0 | 0 | 33 | 4 | 7 |
Variants in SIRT3
This is a list of pathogenic ClinVar variants found in the SIRT3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
11-218857-T-A | not specified | Uncertain significance (Aug 13, 2021) | ||
11-218903-C-T | not specified | Uncertain significance (Apr 28, 2023) | ||
11-218907-G-A | SIRT3-related disorder | Benign (Mar 26, 2019) | ||
11-218945-G-A | not specified | Uncertain significance (Feb 28, 2024) | ||
11-218980-T-A | not specified | Uncertain significance (Sep 10, 2024) | ||
11-218999-C-G | not specified | Uncertain significance (Apr 15, 2024) | ||
11-219011-C-T | not specified | Uncertain significance (Jul 07, 2024) | ||
11-219017-C-T | not specified | Uncertain significance (Sep 27, 2021) | ||
11-224091-C-A | not specified | Uncertain significance (Jan 30, 2024) | ||
11-224101-G-A | not specified | Uncertain significance (May 26, 2023) | ||
11-224107-G-C | not specified | Uncertain significance (Jun 19, 2024) | ||
11-224158-G-A | not specified | Uncertain significance (Jan 30, 2024) | ||
11-224179-C-T | not specified | Uncertain significance (Nov 17, 2022) | ||
11-224194-C-T | SIRT3-related disorder | Likely benign (Mar 09, 2022) | ||
11-224204-C-T | SIRT3-related disorder | Benign (Oct 28, 2019) | ||
11-224215-G-A | not specified | Uncertain significance (Jun 04, 2024) | ||
11-224219-C-G | not specified | Uncertain significance (Jun 29, 2023) | ||
11-230453-C-T | not specified | Uncertain significance (Sep 06, 2022) | ||
11-230474-G-T | Benign (Aug 17, 2018) | |||
11-230508-A-G | not specified | Uncertain significance (Aug 12, 2024) | ||
11-230549-G-A | not specified | Uncertain significance (Oct 25, 2022) | ||
11-232998-C-T | not specified | Uncertain significance (Jan 23, 2023) | ||
11-233024-A-G | not specified | Uncertain significance (Sep 14, 2022) | ||
11-233067-C-T | SIRT3-related disorder | Benign (Nov 27, 2019) | ||
11-233068-G-C | not specified | Uncertain significance (Mar 15, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SIRT3 | protein_coding | protein_coding | ENST00000382743 | 7 | 21474 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.000163 | 0.889 | 125622 | 1 | 125 | 125748 | 0.000501 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.0262 | 226 | 227 | 0.995 | 0.0000130 | 2507 |
Missense in Polyphen | 56 | 61.328 | 0.91312 | 680 | ||
Synonymous | -1.12 | 113 | 98.9 | 1.14 | 0.00000609 | 858 |
Loss of Function | 1.45 | 8 | 13.8 | 0.579 | 6.74e-7 | 166 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000351 | 0.000351 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00 | 0.00 |
Finnish | 0.000139 | 0.000139 |
European (Non-Finnish) | 0.000890 | 0.000888 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.000327 | 0.000294 |
Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: NAD-dependent protein deacetylase (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500, PubMed:24252090, PubMed:19535340). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500, PubMed:24252090). Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5PO (PubMed:16788062, PubMed:18680753, PubMed:24121500, PubMed:24252090, PubMed:19535340). Contributes to the regulation of the cellular energy metabolism (PubMed:24252090). Important for regulating tissue-specific ATP levels (PubMed:18794531). In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription (PubMed:23283301). {ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852, ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:24121500, ECO:0000269|PubMed:24252090}.;
- Pathway
- Central carbon metabolism in cancer - Homo sapiens (human);Energy Metabolism;Mitochondrial biogenesis;NAD metabolism, sirtuins and aging;NAD+ metabolism;NAD+ biosynthetic pathways;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;Signaling events mediated by HDAC Class III;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.134
Intolerance Scores
- loftool
- 0.920
- rvis_EVS
- 0.49
- rvis_percentile_EVS
- 79.46
Haploinsufficiency Scores
- pHI
- 0.0809
- hipred
- Y
- hipred_score
- 0.505
- ghis
- 0.464
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.854
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sirt3
- Phenotype
- immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype;
Gene ontology
- Biological process
- protein ADP-ribosylation;protein deacetylation;mitochondrion organization;aging;aerobic respiration;histone deacetylation;positive regulation of insulin secretion;peptidyl-lysine deacetylation;negative regulation of ERK1 and ERK2 cascade;negative regulation of reactive oxygen species metabolic process
- Cellular component
- cytoplasm;mitochondrion;mitochondrial matrix;protein-containing complex
- Molecular function
- NAD+ ADP-ribosyltransferase activity;protein binding;zinc ion binding;NAD-dependent histone deacetylase activity;enzyme binding;NAD-dependent protein deacetylase activity;sequence-specific DNA binding;NAD+ binding