GeneBe

SIRT3

sirtuin 3, the group of Sirtuins

Basic information

Region (hg38): 11:215030-236931

Links

ENSG00000142082 ∙ NCBI:23410 ∙ OMIM:604481 ∙ HGNC:14931 ∙ Uniprot:Q9NTG7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIRT3 gene.

  • not_specified (75 variants)
  • SIRT3-related_disorder (6 variants)
  • not_provided (2 variants)

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. These statistics are base on transcript: NM_000012239.6. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
2
clinvar
 4
missense
71
clinvar
5
clinvar
2
clinvar
 78
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total 0 0 71 7 4
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SIRT3protein_codingprotein_codingENST00000382743 721474
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.0001630.88912562211251257480.000501
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.02622262270.9950.00001302507
Missense in Polyphen5661.3280.91312680
Synonymous-1.1211398.91.140.00000609858
Loss of Function1.45813.80.5796.74e-7166

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003510.000351
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.0001390.000139
European (Non-Finnish)0.0008900.000888
Middle Eastern0.000.00
South Asian0.0003270.000294
Other0.0003260.000326

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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