SIRT7
protein-codingsirtuin 7, the group of Sirtuins
Gene summary
This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class IV of the sirtuin family. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.4 kbGenCC 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 SIRT7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016538.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 48 | 1 | 49 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 49 | 2 | 0 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057622.1 | 10 | MANE Select | |
| Ensembl | ENSP00000329466.6 | 10 | MANE Select | |
| Ensembl | ENSP00000461044.1 | 4 | Standard | |
| Ensembl | ENSP00000459524.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sirt7 | Danio rerio | Structure: hematopoietic progenitor cell differentiation Quality: decreased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- NAD+ metabolism
- NAD+ biosynthetic pathways
- Signaling events mediated by HDAC Class III
Biological Process
- negative regulation of transcription by RNA polymerase II
- positive regulation of transcription involved in exit from mitosis
- rRNA transcription
- histone H3 deacetylation
- histone H4 deacetylation
Molecular Function
- chromatin binding
- protein binding
- metal ion binding
- NAD+ binding
- NAD-dependent histone deacetylase activity (H3-K18 specific)
Cellular Component
- nucleolus
- nucleolus organizer region
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328666
- Coding exons
- 10
- Length
- 9385
- Individuals with no LoFs
- 125641
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125648
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.885 | 202 | 241 | 0.839 | 0.0000156 | 2535 |
| Missense (PolyPhen) | 49 | 83.233 | 0.58871 | 892 | ||
| Synonymous | -2.13 | 135 | 107 | 1.26 | 0.00000737 | 836 |
| Loss of Function | 2.00 | 8 | 16.9 | 0.475 | 7.19e-7 | 208 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: NAD-dependent protein deacetylase that specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac). In contrast to other histone deacetylases, displays selectivity for a single histone mark, H3K18Ac, directly linked to control of gene expression. H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors. SIRT7 thereby acts as a transcription repressor. Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells. These data suggest that SIRT7 may play a key role in oncogenic transformation by suppresses expression of tumor suppressor genes by locus-specific deacetylation of H3K18Ac at promoter regions. Also required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis: promotes the association of RNA polymerase I with the rDNA promoter region and coding region. Stimulates transcription activity of the RNA polymerase I complex. May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation. {ECO:0000269|PubMed:16618798, ECO:0000269|PubMed:19174463, ECO:0000269|PubMed:22722849}.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- LoFtool
- 0.538
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 45.13
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.873
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |