SESN1

Chr 6

sestrin 1

Also known as: PA26, SEST1

NCBI Gene: 27244ENSG00000080546UniProt: Q9Y6P5

This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the cellular response to DNA damage and oxidative stress. The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential marker for exposure to radiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

77
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SESN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 57 VUS of 77 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.66LOEUF
pLI 0.001
Z-score 2.88
OE 0.39 (0.24–0.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.05Z-score
OE missense 0.83 (0.75–0.92)
251 obs / 302.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.24–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.75–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 10 / 25.8Missense obs/exp: 251 / 302.3Syn Z: -0.46

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
VUS57
20
Pathogenic
57
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
0
0
0
VUS
0
53
4
0
57
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total05324077

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SESN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SESTRIN 1; SESN1
MIM #606103 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3.
Zhang C et al.·Hum Cell
2022
TP53 and TP53-associated genes are correlated with the prognosis of paediatric neuroblastoma.
Wang H et al.·BMC Genom Data
2022
Overexpression of SESN1 improves mitochondrial damage and mitophagy, a potential therapeutic strategy for cognitive dysfunction after anaesthesia.
Sun L et al.·Eur J Neurosci
2024
Circulating Sestrin Levels Are Increased in Hypertension Patients.
Fang C et al.·Dis Markers
2020Cohort
Mutant p53 blocks SESN1/AMPK/PGC-1α/UCP2 axis increasing mitochondrial O(2-)· production in cancer cells.
Cordani M et al.·Br J Cancer
2018
A cross-talk between sestrins, chronic inflammation and cellular senescence governs the development of age-associated sarcopenia and obesity.
Livshits G et al.·Ageing Res Rev
2023Review
Blood RNA sequencing shows overlapping gene expression across COPD phenotype domains.
Ghosh AJ et al.·Thorax
2022
Sestrins increase in patients with coronary artery disease and associate with the severity of coronary stenosis.
Ye J et al.·Clin Chim Acta
2017Cohort
Extracellular vesicles from long COVID patients promote RUNX2-mediated cellular stress via dysregulated miR-204 and p53 pathway activation.
Dalle Carbonare L et al.·Cell Commun Signal
2025Cohort
Upregulation of sestrins protect atriums against oxidative damage and fibrosis in human and experimental atrial fibrillation.
Dong Z et al.·Sci Rep
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Exercise preconditioning prevents immobilization-induced skeletal muscle atrophy by activating Prmt1-p38/ATF2-Sesn1 signaling axis in C57BL/6J mice.
Yang X et al.·Sports Med Health Sci
2026🔓 Open Access
miR-200b-3p affects the proliferation and differentiation of chicken preadipocytes by modulating SESN1 expression through competition with CircADGRF5.
Yuan P et al.·Poult Sci
2025🔓 Open Access
p53-regulated SESN1 and SESN2 regulate cell proliferation and cell death through control of STAT3.
Haidurov A et al.·Cell Commun Signal
2025🔓 Open Access
SESN1 negatively regulates STING1 to maintain innate immune homeostasis.
Xu L et al.·Autophagy
2025
Evaluating SORT1 and SESN1 genes expression in peripheral blood mononuclear cells and oxidative stress status in patients with coronary artery disease.
Ghiasvand T et al.·BMC Genom Data
2024🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools