GeneBe

SIRT3

protein-coding

sirtuin 3, the group of Sirtuins

Gene summary

SIRT3 encodes a member of the sirtuin family of class III histone deacetylases, homologs to the yeast Sir2 protein. The encoded protein is found exclusively in mitochondria, where it can eliminate reactive oxygen species, inhibit apoptosis, and prevent the formation of cancer cells. SIRT3 has far-reaching effects on nuclear gene expression, cancer, cardiovascular disease, neuroprotection, aging, and metabolic control. [provided by RefSeq, May 2019]

MANE transcript

NM_012239.6

Inheritance

—

ClinVar variants

U:87B:12

Top phenotype

SIRT3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr11:215,030-236,931

External References & Databases

Ensembl (ENSG00000142082)NCBI Gene (23410)OMIM (604481)HGNC:14931GenCCUniProt (Q9NTG7)AlphaFoldClinVar (SIRT3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~21.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SIRT3 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 87
SIRT3-related disorderTotal: 7
not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012239.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
3
clinvar
2
clinvar
 7
missense
83
clinvar
5
clinvar
2
clinvar
 90
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total00878499
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 105 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012239.6RefSeqNP_036371.17MANE Select
ENST00000382743.9EnsemblENSP00000372191.47MANE Select
NM_001017524.3RefSeqNP_001017524.16Standard
NM_001370310.1RefSeqNP_001357239.17Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Central carbon metabolism in cancer - Homo sapiens (human)
  • Energy Metabolism
  • Mitochondrial biogenesis
  • NAD metabolism, sirtuins and aging
  • NAD+ metabolism

Biological Process

  • protein ADP-ribosylation
  • protein deacetylation
  • mitochondrion organization
  • aging
  • aerobic respiration

Molecular Function

  • NAD+ ADP-ribosyltransferase activity
  • protein binding
  • zinc ion binding
  • NAD-dependent histone deacetylase activity
  • enzyme binding

Cellular Component

  • cytoplasm
  • mitochondrion
  • mitochondrial matrix
  • protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000382743
Coding exons
7
Length
21474
Individuals with no LoFs
125622
Homozygous LoFs
1
Heterozygous LoFs
125
Defined
125748
p
0.000501
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.02622262270.9950.00001302507
Missense (PolyPhen)5661.3280.91312680
Synonymous-1.1211398.91.140.00000609858
Loss of Function1.45813.80.5796.74e-7166

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.000140.00014rare
European (Non-Finnish)0.000890.00089rare
South Asian0.000330.00029rare
Other0.000330.00033rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.134

Intolerance Scores

LoFtool
0.920
RVIS EVS
0.49
RVIS percentile EVS
79.46

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.854

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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