PES1

Chr 22

prostaglandin-endoperoxide synthase 1

Also known as: COX1, COX3, PCOX1, PES-1, PGG/HS, PGHS-1, PGHS1, PHS1

NCBI Gene: 5742ENSG00000100029UniProt: O00541

This is one of two genes encoding similar enzymes that catalyze the conversion of arachidonate to prostaglandin. The encoded protein regulates angiogenesis in endothelial cells, and is inhibited by nonsteroidal anti-inflammatory drugs such as aspirin. Based on its ability to function as both a cyclooxygenase and as a peroxidase, the encoded protein has been identified as a moonlighting protein. The protein may promote cell proliferation during tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2021]

135
ClinVar variants
19
Pathogenic / LP
0.72
pLI score
0
Active trials
Clinical Summary— PES1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 92 VUS of 135 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.38LOEUF
pLI 0.719
Z-score 4.38
OE 0.20 (0.11–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.31Z-score
OE missense 0.81 (0.73–0.89)
301 obs / 372.2 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.0.20 (0.11–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.89)
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.1.01
0≤1.21.6
LoF obs/exp: 7 / 34.9Missense obs/exp: 301 / 372.2Syn Z: -0.10

ClinVar Variant Classifications

135 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic1
VUS92
Likely Benign4
Benign1
18
Pathogenic
1
Likely Pathogenic
92
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
1
0
1
VUS
0
88
4
0
92
Likely Benign
0
3
0
1
4
Benign
0
0
0
1
1
Total091232116

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

View in ClinVar →

Protein Context — Lollipop Plot

PES1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Emerging role of PES1 in disease: A promising therapeutic target?
Yuan S et al.·Gene
2025Review
PES1 is a biomarker of head and neck squamous cell carcinoma and is associated with the tumor microenvironment.
He Y et al.·Cancer Med
2023
PES1 enhances proliferation and tumorigenesis in hepatocellular carcinoma via the PI3K/AKT pathway.
Wang J et al.·Life Sci
2019
PES1 promotes BET inhibitors resistance and cells proliferation through increasing c-Myc expression in pancreatic cancer.
Jin X et al.·J Exp Clin Cancer Res
2019
Pescadillo ribosomal biogenesis factor 1 reduction suppresses tumour growth and renders chemosensitivity of head and neck squamous cell carcinoma.
Li D et al.·Cancer Med
2023
PES1 promotes breast cancer by differentially regulating ERα and ERβ.
Cheng L et al.·J Clin Invest
2012
PES1 differentially regulates the expression of ERα and ERβ in ovarian cancer.
Li J et al.·IUBMB Life
2013
Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex.
Grimm T et al.·Nucleic Acids Res
2006
Pescadillo ribosomal biogenesis factor 1 and programmed death-ligand 1 in gastric and head and neck squamous cell carcinoma.
Hu XN et al.·World J Gastroenterol
2025
Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations.
Hao BB et al.·Acta Pharmacol Sin
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools