SESN3
protein-codingsestrin 3
Gene summary
This gene encodes a member of the sestrin family of stress-induced proteins. The encoded protein reduces the levels of intracellular reactive oxygen species induced by activated Ras downstream of RAC-alpha serine/threonine-protein kinase (Akt) and FoxO transcription factor. The protein is required for normal regulation of blood glucose, insulin resistance and plays a role in lipid storage in obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.0 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 SESN3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144665.4. 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 | 42 | 42 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 44 | 0 | 1 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_653266.2 | 10 | MANE Select | |
| Ensembl | ENSP00000441927.1 | 10 | MANE Select | |
| RefSeq | NP_001258523.1 | 7 | Standard | |
| Ensembl | ENSP00000278499.2 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p53 signaling pathway - Homo sapiens (human)
- Longevity regulating pathway - Homo sapiens (human)
- TP53 Regulates Metabolic Genes
- Angiopoietin Like Protein 8 Regulatory Pathway
- miRNA regulation of p53 pathway in prostate cancer
Biological Process
- positive regulation of macroautophagy
- response to insulin
- cellular response to amino acid starvation
- TORC2 signaling
- cellular response to glucose starvation
Molecular Function
- protein binding
- oxidoreductase activity, acting on peroxide as acceptor
- leucine binding
Cellular Component
- nucleus
- cytoplasm
- TORC2 complex
- GATOR2 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000536441
- Coding exons
- 10
- Length
- 67002
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125726
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.61 | 149 | 270 | 0.552 | 0.0000139 | 3246 |
| Missense (PolyPhen) | 49 | 114.39 | 0.42835 | 1375 | ||
| Synonymous | 1.20 | 76 | 90.5 | 0.840 | 0.00000422 | 917 |
| Loss of Function | 3.78 | 5 | 25.7 | 0.195 | 0.00000150 | 304 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May function as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway (PubMed:25263562). May also regulate the insulin-receptor signaling pathway through activation of TORC2 (By similarity). This metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). {ECO:0000250|UniProtKB:P58004, ECO:0000250|UniProtKB:Q9CYP7, ECO:0000269|PubMed:25263562}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.109
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.302
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |