SIRT6

sirtuin 6, the group of Sirtuins

Basic information

Region (hg38): 19:4174108-4182566

Links

ENSG00000077463 ∙ NCBI:51548 ∙ OMIM:606211 ∙ HGNC:14934 ∙ Uniprot:Q8N6T7 ∙ 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 SIRT6 gene.

• Inborn genetic diseases (21 variants)
• not provided (9 variants)
• Premature ovarian failure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIRT6 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				4		4
missense		1	21	2	1	25
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	1	22	6	1

Highest pathogenic variant AF is 0.0000197

Variants in SIRT6

This is a list of pathogenic ClinVar variants found in the SIRT6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-4174663-G-A		not specified	Uncertain significance (Feb 21, 2024)
19-4174682-G-A		not specified	Uncertain significance (May 17, 2023)
19-4174687-C-T		not specified	Uncertain significance (Jun 29, 2022)
19-4174700-C-T		not specified	Uncertain significance (May 05, 2022)
19-4174724-C-T		not specified	Uncertain significance (Jan 10, 2022)
19-4174725-G-C		not specified	Uncertain significance (Sep 28, 2021)
19-4174730-G-T		not specified	Uncertain significance (Dec 02, 2021)
19-4174748-C-A			Likely benign (Dec 31, 2019)
19-4174748-C-T		not specified	Uncertain significance (Jul 12, 2022)
19-4174761-G-C			Likely benign (Dec 31, 2019)
19-4174803-G-A			Likely benign (May 31, 2018)
19-4174813-C-T		not specified	Uncertain significance (Jul 19, 2022)
19-4174814-G-A		not specified	Uncertain significance (Sep 01, 2021)
19-4174822-G-T		not specified	Uncertain significance (Feb 10, 2022)
19-4174862-C-T			Benign (Jun 10, 2018)
19-4174894-C-T		not specified	Uncertain significance (May 18, 2023)
19-4174900-A-T		not specified	Uncertain significance (Aug 21, 2023)
19-4174907-C-T		not specified	Uncertain significance (May 30, 2023)
19-4174943-G-A		Long QT syndrome	Uncertain significance (-)
19-4174953-A-G			Benign (May 22, 2019)
19-4175051-C-T		not specified	Uncertain significance (Jan 27, 2022)
19-4175062-C-T		not specified	Uncertain significance (Sep 20, 2023)
19-4175063-G-A		not specified	Uncertain significance (Oct 26, 2022)
19-4175107-C-T		not specified	Uncertain significance (Apr 07, 2022)
19-4175693-C-T		not specified	Uncertain significance (Jul 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIRT6	protein_coding	protein_coding	ENST00000337491	8	8496

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0391	0.955	125706	0	11	125717	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.605	190	215	0.884	0.0000145	2212
Missense in Polyphen		65	87.935	0.73918		866
Synonymous	0.401	94	99.1	0.949	0.00000736	760
Loss of Function	2.40	5	15.1	0.332	9.21e-7	147

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000296	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000447	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.0000329	0.0000327
Other	0.000176	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF- kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate. {ECO:0000250, ECO:0000269|PubMed:18337721, ECO:0000269|PubMed:19135889, ECO:0000269|PubMed:19625767, ECO:0000269|PubMed:20829486, ECO:0000269|PubMed:21362626}.
• Pathway: Central carbon metabolism in cancer - Homo sapiens (human);Thermogenesis - Homo sapiens (human);SREBF and miR33 in cholesterol and lipid homeostasis;NAD+ metabolism;NAD+ biosynthetic pathways;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Vitamin B3 (nicotinate and nicotinamide) metabolism;Processing of DNA double-strand break ends (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.505
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.27

Haploinsufficiency Scores

• pHI: 0.192
• hipred: Y
• hipred_score: 0.676
• ghis: 0.494

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sirt6
• Phenotype: hematopoietic system phenotype; reproductive system phenotype; 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); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; craniofacial phenotype; vision/eye phenotype; growth/size/body region 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: post-embryonic cardiac muscle cell growth involved in heart morphogenesis;base-excision repair;protein ADP-ribosylation;negative regulation of cell population proliferation;regulation of double-strand break repair via homologous recombination;protein destabilization;response to nutrient levels;positive regulation of chromatin silencing at telomere;positive regulation of telomere maintenance;glucose homeostasis;negative regulation of glycolytic process;negative regulation of transcription, DNA-templated;negative regulation of glucose import;positive regulation of fibroblast proliferation;histone H3-K9 modification;positive regulation of cold-induced thermogenesis;positive regulation of chondrocyte proliferation;positive regulation of telomeric heterochromatin assembly;positive regulation blood vessel branching;positive regulation of vascular endothelial cell proliferation;histone H3-K9 deacetylation;positive regulation of stem cell proliferation
• Cellular component: nucleus;nucleoplasm;nuclear telomeric heterochromatin;nucleolus;cytoplasm
• Molecular function: chromatin binding;transcription corepressor activity;NAD+ ADP-ribosyltransferase activity;NAD(P)+-protein-arginine ADP-ribosyltransferase activity;protein binding;zinc ion binding;NAD-dependent histone deacetylase activity;NAD-dependent protein deacetylase activity;NAD-dependent histone deacetylase activity (H3-K9 specific);NAD+ binding