SESN2
protein-codingsestrin 2
Gene summary
This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions. [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 ~23.0 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 SESN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031459.5. 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 | 5 | 6 | |||
| missense | 74 | 4 | 3 | 81 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 75 | 5 | 8 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_113647.1 | 10 | MANE Select | |
| Ensembl | ENSP00000253063.3 | 10 | MANE Select | |
| Ensembl | ENSP00000532860.1 | 9 | Standard | |
| Ensembl | ENSP00000532861.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- p53 signaling pathway - Homo sapiens (human)
- Longevity regulating pathway - Homo sapiens (human)
- TP53 Regulates Metabolic Genes
- Gene expression (Transcription)
Biological Process
- regulation of protein phosphorylation
- regulation of gluconeogenesis
- fatty acid beta-oxidation
- response to glucose
- positive regulation of macroautophagy
Molecular Function
- GDP-dissociation inhibitor activity
- protein binding
- oxidoreductase activity, acting on peroxide as acceptor
- sulfiredoxin activity
- leucine binding
Cellular Component
- nucleus
- cytoplasm
- mitochondrion
- cytosol
- nucleotide-activated protein kinase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000253063
- Coding exons
- 10
- Length
- 22965
- Individuals with no LoFs
- 125661
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 87
- Defined
- 125748
- p
- 0.000346
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.65 | 218 | 298 | 0.732 | 0.0000189 | 3097 |
| Missense (PolyPhen) | 91 | 141.49 | 0.64314 | 1457 | ||
| Synonymous | -0.290 | 128 | 124 | 1.03 | 0.00000769 | 977 |
| Loss of Function | 1.91 | 14 | 24.1 | 0.580 | 0.00000128 | 259 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.0020 | 0.0020 | notable |
| European (Non-Finnish) | 0.00021 | 0.00021 | rare |
| South Asian | 0.00021 | 0.00020 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Has an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821). {ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:19113821, ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24947615, ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:26586190, ECO:0000269|PubMed:26612684}.;
Recessive Scores
- pRec
- 0.121
Intolerance Scores
- LoFtool
- 0.659
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.911
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |