SIRT5
sirtuin 5, the group of Sirtuins
Basic information
Region (hg38): 6:13574227-13615158
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (51 variants)
- not_provided (1 variants)
- SIRT5-related_disorder (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. These statistics are base on transcript: NM_000012241.5. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 47 | 52 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 47 | 5 | 0 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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