SESN2

sestrin 2

Basic information

Region (hg38): 1:28259518-28282491

Links

ENSG00000130766 ∙ NCBI:83667 ∙ OMIM:607767 ∙ HGNC:20746 ∙ Uniprot:P58004 ∙ 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 SESN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SESN2 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				1	5	6
missense			40	3	3	46
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding						0
Total	0	0	40	4	8

Variants in SESN2

This is a list of pathogenic ClinVar variants found in the SESN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-28259854-G-T		not specified	Uncertain significance (Sep 15, 2022)
1-28259876-C-T		not specified	Uncertain significance (Aug 13, 2021)
1-28259885-A-C		not specified	Uncertain significance (Feb 13, 2024)
1-28259908-G-T		not specified	Uncertain significance (May 23, 2023)
1-28259909-G-A		not specified	Uncertain significance (Jul 30, 2024)
1-28259923-T-A		not specified	Uncertain significance (May 26, 2022)
1-28259923-T-C		not specified	Likely benign (Apr 12, 2022)
1-28269198-C-T			Likely benign (Jun 20, 2018)
1-28269204-C-G		not specified	Uncertain significance (Oct 25, 2024)
1-28269205-G-A		not specified	Uncertain significance (Dec 19, 2023)
1-28269220-G-A		not specified	Uncertain significance (Nov 22, 2023)
1-28269229-C-T		not specified	Uncertain significance (Jan 19, 2025)
1-28271718-G-A			Benign (Apr 20, 2018)
1-28271732-C-T		not specified	Uncertain significance (Mar 21, 2023)
1-28271776-C-T			Benign (Jun 22, 2018)
1-28271801-G-A		not specified	Uncertain significance (Jan 20, 2023)
1-28271801-G-C		not specified	Uncertain significance (Aug 10, 2021)
1-28271851-C-T		not specified	Uncertain significance (Dec 25, 2024)
1-28272294-G-A		not specified	Uncertain significance (Sep 13, 2023)
1-28272318-G-A		not specified	Uncertain significance (Jan 17, 2025)
1-28272326-A-G		not specified	Uncertain significance (Dec 11, 2024)
1-28272397-G-A			Likely benign (Oct 01, 2022)
1-28272408-G-A		not specified	Uncertain significance (Apr 08, 2024)
1-28272410-G-A		not specified	Uncertain significance (Jan 10, 2022)
1-28272597-G-C		not specified	Uncertain significance (Aug 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SESN2	protein_coding	protein_coding	ENST00000253063	10	22965

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.19e-7	0.953	125661	0	87	125748	0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	218	298	0.732	0.0000189	3097
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000211	0.000211
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00199	0.00199
European (Non-Finnish)	0.000213	0.000211
Middle Eastern	0.000218	0.000217
South Asian	0.000205	0.000196
Other	0.000820	0.000815

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.659
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.86

Haploinsufficiency Scores

• pHI: 0.611
• hipred: Y
• hipred_score: 0.702
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.911

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sesn2
• Phenotype: renal/urinary system phenotype; liver/biliary system phenotype; respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of protein phosphorylation;regulation of gluconeogenesis;fatty acid beta-oxidation;response to glucose;positive regulation of macroautophagy;negative regulation of cell growth;DNA damage response, signal transduction by p53 class mediator;mitochondrial DNA metabolic process;response to insulin;cellular response to amino acid starvation;cellular response to oxidative stress;positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress;cellular response to glucose starvation;glucose homeostasis;protein kinase B signaling;glucose import;triglyceride homeostasis;cellular response to amino acid stimulus;cellular response to leucine;reactive oxygen species metabolic process;cellular oxidant detoxification;positive regulation of protein localization to nucleus;regulation of response to reactive oxygen species;negative regulation of translation in response to endoplasmic reticulum stress;negative regulation of TORC1 signaling;positive regulation of lipophagy;cellular response to leucine starvation;regulation of cAMP-dependent protein kinase activity
• Cellular component: nucleus;cytoplasm;mitochondrion;cytosol;nucleotide-activated protein kinase complex;TORC2 complex;GATOR2 complex;Atg1/ULK1 kinase complex
• Molecular function: GDP-dissociation inhibitor activity;protein binding;oxidoreductase activity, acting on peroxide as acceptor;sulfiredoxin activity;leucine binding