SIRT3

sirtuin 3, the group of Sirtuins

Basic information

Region (hg38): 11:215029-236931

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.

• Inborn genetic diseases (19 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.

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						0
missense			19		2	21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	0	2

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)
11-219017-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)
11-224158-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)
11-224219-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)
11-230549-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)
11-233168-G-A		not specified	Uncertain significance (Oct 25, 2023)
11-233201-C-T		not specified	Uncertain significance (Apr 05, 2023)
11-233206-C-A		SIRT3-related disorder	Likely benign (Jul 27, 2020)
11-233210-G-A		not specified	Uncertain significance (Dec 21, 2023)
11-233210-G-T		not specified	Uncertain significance (Nov 05, 2021)
11-233212-C-A		SIRT3-related disorder	Benign (Oct 23, 2019)
11-233364-G-C		not specified	Uncertain significance (Jul 12, 2022)

GnomAD

Source: gnomAD

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: 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

	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