SIRT5

sirtuin 5, the group of Sirtuins

Basic information

Region (hg38): 6:13574226-13615158

Links

ENSG00000124523 ∙ NCBI:23408 ∙ OMIM:604483 ∙ HGNC:14933 ∙ Uniprot:Q9NXA8 ∙ 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 SIRT5 gene.

• Inborn genetic diseases (17 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIRT5 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			15	2		17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	2	0

Variants in SIRT5

This is a list of pathogenic ClinVar variants found in the SIRT5 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-13584199-G-T		not specified	Uncertain significance (Feb 28, 2024)
6-13588417-C-T		not specified	Uncertain significance (Mar 30, 2022)
6-13588418-C-T		not specified	Uncertain significance (Aug 30, 2021)
6-13591709-G-A		not specified	Likely benign (Jan 19, 2022)
6-13591724-A-G		not specified	Uncertain significance (Feb 27, 2024)
6-13591733-G-A		not specified	Uncertain significance (Sep 26, 2022)
6-13591786-G-C		not specified	Uncertain significance (Nov 09, 2022)
6-13591799-G-A		not specified	Uncertain significance (Oct 25, 2023)
6-13591801-C-G		not specified	Uncertain significance (Jun 05, 2023)
6-13591825-G-A		not specified	Likely benign (Jul 26, 2022)
6-13591846-G-A		not specified	Uncertain significance (Nov 14, 2023)
6-13591858-C-A		not specified	Uncertain significance (Apr 25, 2022)
6-13591859-G-A		not specified	Uncertain significance (Mar 22, 2023)
6-13591864-G-A		not specified	Uncertain significance (Jan 12, 2024)
6-13595512-G-A		not specified	Uncertain significance (Apr 19, 2023)
6-13595515-G-A		not specified	Uncertain significance (Aug 16, 2021)
6-13595525-A-G		not specified	Uncertain significance (Jun 03, 2022)
6-13595531-A-G		not specified	Uncertain significance (May 27, 2022)
6-13599036-G-A		not specified	Uncertain significance (Jun 14, 2022)
6-13599064-G-A		not specified	Uncertain significance (Jan 03, 2024)
6-13599067-C-G		not specified	Uncertain significance (Jan 11, 2023)
6-13599103-C-T		not specified	Uncertain significance (Apr 24, 2023)
6-13600840-A-G		not specified	Uncertain significance (Mar 07, 2023)
6-13600919-C-T		not specified	Likely benign (Oct 17, 2023)
6-13604478-A-T			not provided (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIRT5	protein_coding	protein_coding	ENST00000606117	8	39975

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.66e-10	0.283	125651	0	97	125748	0.000386

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.140	188	194	0.972	0.0000118	1986
Missense in Polyphen		67	65.854	1.0174		655
Synonymous	-0.329	75	71.5	1.05	0.00000423	645
Loss of Function	0.769	16	19.7	0.813	0.00000140	187

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000490	0.000489
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000361	0.000360
Middle Eastern	0.000598	0.000598
South Asian	0.00101	0.00101
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation (PubMed:29180469). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX. {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693, ECO:0000269|PubMed:29180469}.
• Pathway: NAD+ metabolism;NAD+ biosynthetic pathways;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.162

Intolerance Scores

• loftool: 0.957
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.61

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.449
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.723

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sirt5
• Phenotype: homeostasis/metabolism phenotype; normal phenotype

Gene ontology

• Biological process: chromatin silencing;protein ADP-ribosylation;protein deacetylation;mitochondrion organization;regulation of ketone biosynthetic process;negative regulation of cardiac muscle cell apoptotic process;response to nutrient levels;protein demalonylation;peptidyl-lysine demalonylation;protein desuccinylation;peptidyl-lysine desuccinylation;protein deglutarylation;peptidyl-lysine deglutarylation;negative regulation of reactive oxygen species metabolic process
• Cellular component: nucleus;mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;mitochondrial matrix;cytosol
• Molecular function: NAD+ ADP-ribosyltransferase activity;zinc ion binding;NAD-dependent protein deacetylase activity;protein-malonyllysine demalonylase activity;protein-succinyllysine desuccinylase activity;protein-glutaryllysine deglutarylase activity;NAD+ binding