PGR

protein-coding

progesterone receptor, the group of Nuclear receptor subfamily 3 group C

Gene summary

This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015]

MANE transcript

NM_000926.4

Inheritance

—

ClinVar variants

U:119B:21

Top phenotype

Breast neoplasm

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr11:101,029,624-101,129,813

External References & Databases

Ensembl (ENSG00000082175)

Transcript & Mutation Effects

hg38 • Region Span ~100.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PGR variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 113

not providedTotal: 21

Breast neoplasmTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000926.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	7 clinvar	8 clinvar	16
missense			116 clinvar	1 clinvar	5 clinvar	122
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	119	8	13	140

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000926.4	RefSeq	NP_000917.3	8	MANE Select
ENST00000325455.10	Ensembl	ENSP00000325120.5	8	MANE Select
NM_001202474.3	RefSeq	NP_001189403.1	8	Standard
NM_001271161.2	RefSeq	NP_001258090.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pgr	Danio rerio	Structure: oocyte stage V Quality: non-functional abnormal

Gene / Model

Organism

Observed Phenotype

pgr

Danio rerio

Structure: oocyte stage V

Quality: non-functional

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oocyte meiosis - Homo sapiens (human)
Breast cancer - Homo sapiens (human)
Estrogen signaling pathway - Homo sapiens (human)
Progesterone-mediated oocyte maturation - Homo sapiens (human)
NHR

Biological Process

ovulation from ovarian follicle
epithelial cell maturation
transcription initiation from RNA polymerase II promoter
signal transduction
cell-cell signaling

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA binding
steroid hormone receptor activity

Cellular Component

nucleoplasm
mitochondrial outer membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325455
Coding exons: 8
Length: 100901
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	426	507	0.840	0.0000242	5880
Missense (PolyPhen)		121	202.08	0.59878		2475
Synonymous	-0.435	224	216	1.04	0.0000106	1983
Loss of Function	3.91	9	33.4	0.269	0.00000165	403

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0.000096	0.000092	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000067	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. {ECO:0000269|PubMed:10757795, ECO:0000269|PubMed:1587864, ECO:0000269|PubMed:9407067, ECO:0000305}.; FUNCTION: Isoform B: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. {ECO:0000269|PubMed:7969170}.;

Recessive Scores

pRec: 0.530

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.499

Gene Damage Prediction

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