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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PGR
progesterone receptor
Chromosome 11 · 11q22.1
NCBI Gene: 5241Ensembl: ENSG00000082175.16HGNC: HGNC:8910UniProt: P06401
793PubMed Papers
20Diseases
32Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneReceptorTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of gene expressionregulation of DNA-templated transcriptionRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription activator activity, RNA polymerase II-specificendometriosiscontraceptioninfertilityacne
✦AI Summary

The progesterone receptor (PGR) is a nuclear receptor that functions as a ligand-activated transcription factor controlling reproductive processes through progesterone signaling. Upon progesterone binding, PGR regulates gene expression via RNA polymerase II-dependent mechanisms and modulates chr11 accessibility to control endometrial and myometrial function 1. PGR protein stability is maintained through multiple regulatory pathways, including SOX4-mediated repression of E3 ubiquitin ligase-driven degradation 2, and PGR mRNA translation is enhanced by METTL3-catalyzed m6A modifications in the 5' UTR in a YTHDF1-dependent manner 3. PGR is essential for endometrial receptivity and embryo implantation, with its expression regulated by histone acetylation marks (H3K27ac) that decline with reproductive aging 4. In endometriosis, progesterone resistance develops through YAP1-mediated upregulation of miR-21-5p, which suppresses PGR expression and impairs decidualization 5. PGR deficiency in endometriotic stromal cells contributes to dysregulated differentiation, inflammation, and enhanced cell survival 6. Additionally, environmental bisphenol exposure can induce breast cancer through direct PGR binding and altered signaling 7. PGR's role extends to myometrial remodeling during pregnancy, where altered PGR occupancy patterns coordinate with transcriptomic changes supporting parturition 1.

Sources cited
1
H3K27ac loss reduces PGR expression and impairs endometrial receptivity in aging
PMID: 40394215
2
METTL3-mediated m6A modification enhances PGR translation via YTHDF1-dependent mechanism during implantation
PMID: 36693099
3
YAP1 inhibits PGR expression through miR-21-5p upregulation, causing progesterone resistance in endometriosis
PMID: 37071897
4
PGR deficiency in endometriotic stromal cells contributes to progesterone resistance and defective differentiation
PMID: 30809650
5
Bisphenols bind to PGR with high affinity and induce its expression, potentially contributing to breast cancer
PMID: 40482448
6
SOX4 maintains PGR protein stability by repressing HERC4-mediated ubiquitin-dependent degradation
PMID: 35244538
7
PGR genome occupancy patterns change between nonpregnant and term pregnant myometrium, regulating genes in glycolytic and calcium signaling pathways
PMID: 31908010
Disease Associationsⓘ20
endometriosisOpen Targets
0.67Moderate
contraceptionOpen Targets
0.60Moderate
infertilityOpen Targets
0.60Moderate
acneOpen Targets
0.60Moderate
breast cancerOpen Targets
0.58Moderate
hemorrhageOpen Targets
0.58Moderate
DysmenorrheaOpen Targets
0.57Moderate
MenorrhagiaOpen Targets
0.57Moderate
leiomyomaOpen Targets
0.57Moderate
premature birthOpen Targets
0.55Moderate
AnorexiaOpen Targets
0.55Moderate
neoplasmOpen Targets
0.53Moderate
CachexiaOpen Targets
0.53Moderate
amenorrheaOpen Targets
0.52Moderate
Cushing syndromeOpen Targets
0.52Moderate
uterine fibroidOpen Targets
0.51Moderate
inborn error of immunityOpen Targets
0.50Moderate
osteoporosisOpen Targets
0.47Moderate
hyperplasiaOpen Targets
0.47Moderate
female infertilityOpen Targets
0.46Moderate
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets32
ASOPRISNILPhase III
Progesterone receptor modulator
endometriosis
CHLORMADINONE ACETATEUNKNOWN
Progesterone receptor modulator
CYPROTERONE ACETATEPhase III
Glucocorticoid receptor antagonist
prostate cancer
DANAZOLApproved
Androgen Receptor agonist
breast fibrocystic disease
DESOGESTRELApproved
Progesterone receptor agonist
contraception
DROSPIRENONEApproved
Mineralocorticoid receptor antagonist
acne
DYDROGESTERONEApproved
Progesterone receptor agonist
Menstrual disorder
ETHYNODIOL DIACETATEApproved
Progesterone receptor agonist
contraception
ETONOGESTRELApproved
Progesterone receptor agonist
contraception
GESTODENEPhase III
Progesterone receptor agonist
contraception
HYDROXYPROGESTERONE CAPROATEApproved
Progesterone receptor agonist
premature birth
LEVONORGESTRELApproved
Progesterone receptor agonist
Menorrhagia
LONAPRISANPhase II
Progesterone receptor antagonist
breast cancer
MEDROXYPROGESTERONE ACETATEApproved
Progesterone receptor agonist
MEGESTROL ACETATEApproved
Progesterone receptor agonist
Anorexia
MIFEPRISTONEApproved
Progesterone receptor antagonist
NOMEGESTROLApproved
Progesterone receptor agonist
contraception
NOMEGESTROL ACETATEApproved
Progesterone receptor agonist
breast cancer
NORELGESTROMINApproved
Progesterone receptor agonist
contraception
NORETHINDRONEApproved
Progesterone receptor agonist
endometriosis
NORETHINDRONE ACETATEApproved
Progesterone receptor agonist
acne
NORGESTIMATEApproved
Progesterone receptor agonist
acne
NORGESTRELApproved
Progesterone receptor agonist
hemorrhage
ONAPRISTONEPhase II
Progesterone receptor antagonist
breast cancer
PF-05019702Phase I
Progesterone receptor antagonist
uterine fibroid
PROGESTERONEApproved
Progesterone receptor agonist
Atypical Endometrial Hyperplasia
SEGESTERONE ACETATEApproved
Progesterone receptor agonist
contraception
TELAPRISTONE ACETATEPhase III
Progesterone receptor modulator
uterine fibroid
TRIMEGESTONEApproved
Progesterone receptor agonist
ULIPRISTALApproved
Progesterone receptor modulator
contraception
ULIPRISTAL ACETATEApproved
Progesterone receptor modulator
contraception
VILAPRISANPhase III
Progesterone receptor modulator
uterine fibroid
Related Genes
HSP90AB1Protein interaction100%PIK3R3Protein interaction100%PIK3R1Protein interaction100%PIK3CBProtein interaction100%PIK3CDProtein interaction100%PIK3CAProtein interaction100%
Tissue Expression6 tissues
Ovary
100%
Heart
61%
Lung
9%
Brain
2%
Liver
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PGRHSP90AB1PIK3R3PIK3R1PIK3CBPIK3CDPIK3CA
PROTEIN STRUCTURE
Preparing viewer…
PDB1SQN · 1.45 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.72Intermediate
Observed/Expected LoF0.38 [0.27–0.55]
RankingsWhere PGR stands among ~20K protein-coding genes
  • #250of 20,598
    Most Researched793 · top 5%
  • #70of 1,025
    FDA-Approved Drug Targets23 · top 10%
  • #3,560of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedPGR
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Endometrial aging is accompanied by H3K27ac and PGR loss.
PMID: 40394215
Nat Aging · 2025
1.00
2
METTL3 is essential for normal progesterone signaling during embryo implantation via m
PMID: 36693099
Proc Natl Acad Sci U S A · 2023
0.90
3
Progesterone Signaling in Endometrial Epithelial Organoids.
PMID: 35681455
Cells · 2022
0.86
4
Epithelioid leiomyosarcoma of broad ligament harboring PGR-NR4A3 and UBR5-PGR gene fusions: a unique case report.
PMID: 34351486
Virchows Arch · 2022
0.82
5
Targeting YAP1 ameliorates progesterone resistance in endometriosis.
PMID: 37071897
Hum Reprod · 2023
0.80