SESN1

sestrin 1

Basic information

Region (hg38): 6:108984309-109094846

Links

ENSG00000080546

∙ NCBI:27244 ∙ OMIM:606103 ∙ HGNC:21595 ∙ Uniprot:Q9Y6P5 ∙ 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 SESN1 gene.

not_specified (48 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SESN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014454.3. 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			48 clinvar			48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	48	0	0

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SESN1	protein_coding	protein_coding	ENST00000436639	10	108383

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000596	0.998	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.05	251	302	0.830	0.0000152	3675
Missense in Polyphen		96	137.2	0.69973		1709
Synonymous	-0.455	106	100	1.06	0.00000498	991
Loss of Function	2.88	10	25.8	0.388	0.00000120	342

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000802	0.000801
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000141	0.0000462
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.00	0.00
South Asian	0.000196	0.000196
Other	0.000489	0.000489

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. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:25263562, PubMed:26449471). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). 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 have an alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (By similarity). {ECO:0000250|UniProtKB:P58004, ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:26449471}.;
Pathway: p53 signaling pathway - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);miRNA Regulation of DNA Damage Response;Mesodermal Commitment Pathway;TP53 Regulates Metabolic Genes;DNA Damage Response;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;Direct p53 effectors (Consensus)

Recessive Scores

pRec: 0.134

Intolerance Scores

loftool: 0.718
rvis_EVS: -0.84
rvis_percentile_EVS: 11.18

Haploinsufficiency Scores

pHI: 0.342
hipred: Y
hipred_score: 0.765
ghis: 0.581

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.838

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Sesn1
Phenotype: hematopoietic system phenotype; immune system phenotype;

Gene ontology

Biological process: positive regulation of macroautophagy;cellular response to amino acid starvation;cellular response to glucose starvation;oxidation-reduction process;cellular response to amino acid stimulus;cellular response to leucine;reactive oxygen species metabolic process;cellular oxidant detoxification;regulation of response to reactive oxygen species;negative regulation of TORC1 signaling;cellular response to leucine starvation
Cellular component: fibrillar center;nucleus;cytoplasm;cytosol;TORC2 complex;GATOR2 complex
Molecular function: protein binding;oxidoreductase activity, acting on peroxide as acceptor;peroxiredoxin activity;leucine binding