PAQR7

Summary

PAQR7 (progestin and adipoQ receptor family member 7, HGNC:23146) is a protein-coding gene on chromosome 1p36.11, encoding Membrane progestin receptor alpha (Q86WK9). Plasma membrane progesterone (P4) receptor coupled to G proteins.

Predicted to enable nuclear steroid receptor activity and steroid binding activity. Predicted to be involved in response to steroid hormone. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 164091 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_178422

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23146
Approved symbol	PAQR7
Name	progestin and adipoQ receptor family member 7
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	mSR, MPRA, PGLP
Ensembl gene	ENSG00000182749
Ensembl biotype	protein_coding
OMIM	607779
Entrez	164091

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000374296, ENST00000675840, ENST00000873976, ENST00000943386

RefSeq mRNA: 1 — MANE Select: NM_178422 NM_178422

CCDS: CCDS267

Canonical transcript exons

ENST00000675840 — 3 exons

Exon	Start	End
ENSE00001463072	25861484	25863861
ENSE00003900209	25870609	25870694
ENSE00003901926	25875488	25875708

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9556 / max 138.9342, expressed in 1661 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11101	3.3634	1476
11099	1.5079	678
11100	1.1412	776
11102	0.9334	622
11103	0.8360	534
11104	0.1737	75

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	98.81	gold quality
kidney epithelium	UBERON:0004819	95.41	silver quality
tendon of biceps brachii	UBERON:0008188	94.76	gold quality
right testis	UBERON:0004534	94.68	gold quality
left testis	UBERON:0004533	94.63	gold quality
upper arm skin	UBERON:0004263	94.20	silver quality
testis	UBERON:0000473	93.20	gold quality
buccal mucosa cell	CL:0002336	91.35	gold quality
right uterine tube	UBERON:0001302	90.75	gold quality
right adrenal gland cortex	UBERON:0035827	90.18	gold quality
right ovary	UBERON:0002118	89.97	gold quality
right adrenal gland	UBERON:0001233	89.84	gold quality
left adrenal gland	UBERON:0001234	89.31	gold quality
ovary	UBERON:0000992	89.15	gold quality
left ovary	UBERON:0002119	88.98	gold quality
left adrenal gland cortex	UBERON:0035825	88.84	gold quality
adrenal cortex	UBERON:0001235	88.80	gold quality
fallopian tube	UBERON:0003889	88.69	gold quality
lower esophagus mucosa	UBERON:0035834	88.47	gold quality
medial globus pallidus	UBERON:0002477	88.30	gold quality
stromal cell of endometrium	CL:0002255	87.91	gold quality
adrenal gland	UBERON:0002369	87.89	gold quality
skin of leg	UBERON:0001511	87.51	gold quality
adult mammalian kidney	UBERON:0000082	87.36	gold quality
metanephros cortex	UBERON:0010533	86.88	gold quality
seminal vesicle	UBERON:0000998	86.75	gold quality
skin of abdomen	UBERON:0001416	86.56	gold quality
placenta	UBERON:0001987	86.40	gold quality
cortex of kidney	UBERON:0001225	86.38	gold quality
duodenum	UBERON:0002114	86.29	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	506.38
E-ANND-3	yes	10.99
E-MTAB-9801	yes	6.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PAQR7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-6747-3P	97.73	64.84	1596

Literature-anchored findings (GeneRIF, showing 13)

• cDNAs for the mPR alpha subtypes from spotted seatrout (st-mPRalpha) and humans (hu-mPRalpha) encode progestin receptors that display many functional characteristics of G protein-coupled receptors. (PMID:17082257)
• Heterologous expression of MPRA in yeast confirms its ability to function as a membrane progesterone receptor. (PMID:18603275)
• mPRalpha is an intermediary in progestin stimulation of sperm motility in humans by a mechanism involving G-protein activation (PMID:19071147)
• Data show abundant mPRalpha (PAQR7), mPRbeta (PAQR8), and mPRgamma (PAQR5), but not classical nuclear PR (A or B isoforms) mRNA expression and mPRalpha protein expression in a panel of commonly used ovarian cancer cell lines. (PMID:21761364)
• Utilizing both genetic and pharmacologic approaches, the authors establish that sex steroid effects on human melanin synthesis are mediated by the membrane-bound, steroid hormone receptors G protein-coupled estrogen receptor (GPER), and progestin and adipoQ receptor 7 (PAQR7). (PMID:27115344)
• The effects of progesterone treatment on the expression levels of progesterone receptor membrane component 1 (PGRMC1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1), and progestin and adipoQ receptor 7 (PAQR7) on both mRNA and protein levels were investigated in spheroids derived from human glioma cell lines U-87 MG and LN-229. (PMID:27340667)
• The results suggest that progesterone induces vascular smooth muscle cell relaxation by reducing cellular calcium levels through mPRalpha-induced alterations in multiple signaling pathways. (PMID:31416049)
• Membrane progesterone receptor alpha (mPRalpha/PAQR7) promotes migration, proliferation and BDNF release in human Schwann cell-like differentiated adipose stem cells. (PMID:33930460)
• Establishment of a steroid binding assay for membrane progesterone receptor alpha (PAQR7) by using graphene quantum dots (GQDs). (PMID:35007844)
• Membrane Progesterone Receptor alpha (mPRalpha/PAQR7) Promotes Survival and Neurite Outgrowth of Human Neuronal Cells by a Direct Action and Through Schwann Cell-like Stem Cells. (PMID:35974286)
• Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor alpha (mPRalpha/PAQR7). (PMID:36967764)
• Membrane progesterone receptors on the cell membrane: A review highlighting potential export motifs in mPRalpha regulating its trafficking to the cell surface. (PMID:37558174)
• Progestin and adipoQ receptor 7 (PAQR7) mediate the anti-apoptotic effect of P4 on human granulosa cells and its deficiency reduces ovarian function in female mice. (PMID:38317224)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	paqr7b	ENSDARG00000034907
mus_musculus	Paqr7	ENSMUSG00000037348
rattus_norvegicus	Paqr7	ENSRNOG00000022054
drosophila_melanogaster	AdipoR	FBGN0038984
caenorhabditis_elegans		WBGENE00016610
caenorhabditis_elegans		WBGENE00019643

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD (ENSG00000108960), MMD2 (ENSG00000136297), PAQR5 (ENSG00000137819), ADIPOR1 (ENSG00000159346), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Membrane progestin receptor alpha — Q86WK9 (reviewed: Q86WK9)

Alternative names: Membrane progesterone P4 receptor alpha, Membrane progesterone receptor alpha, Progesterone and adipoQ receptor family member 7, Progestin and adipoQ receptor family member 7, Progestin and adipoQ receptor family member VII

All UniProt accessions (1): Q86WK9

UniProt curated annotations — full annotation on UniProt →

Function. Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(i) mediated pathway. May be involved in oocyte maturation. Involved in neurosteroid inhibition of apoptosis. Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in a wide range of tissues including ovary, testis, placenta, uterus and bladder.

Miscellaneous. Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).

Similarity. Belongs to the ADIPOR family.

RefSeq proteins (1): NP_848509* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family

Pfam: PF03006

UniProt features (18 total): topological domain 8, transmembrane region 7, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WK9-F1	90.13	0.78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_OOGENESIS, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, BIOCARTA_MPR_PATHWAY, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID

GO Biological Process (4): oogenesis (GO:0048477), response to steroid hormone (GO:0048545), cell differentiation (GO:0030154), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518)

GO Molecular Function (4): nuclear steroid receptor activity (GO:0003707), steroid binding (GO:0005496), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
germ cell development	1
female gamete generation	1
response to hormone	1
response to lipid	1
cellular developmental process	1
steroid hormone receptor signaling pathway	1
nuclear receptor-mediated signaling pathway	1
nuclear receptor activity	1
nuclear receptor-mediated steroid hormone signaling pathway	1
lipid binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAQR7	PGRMC1	O00264	882
PAQR7	PGRMC2	O15173	820
PAQR7	PAQR6	Q6TCH4	816
PAQR7	ADIPOQ	Q15848	800
PAQR7	PGR	P06401	633
PAQR7	PPARA	Q07869	597
PAQR7	SERBP1	Q8NC51	572
PAQR7	PAQR5	Q9NXK6	531
PAQR7	CYB5D2	Q8WUJ1	496
PAQR7	PAQR8	Q8TEZ7	496
PAQR7	GPER1	Q99527	470
PAQR7	MMD	Q15546	444
PAQR7	PPARG	P37231	437
PAQR7	NENF	Q9UMX5	426
PAQR7	NPTXR	O95502	418

IntAct

15 interactions, top by confidence:

A	B	Type	Score
FAM209A	PAQR7	psi-mi:“MI:0915”(physical association)	0.560
PAQR7	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
HTT	PAQR7	psi-mi:“MI:0915”(physical association)	0.560
STAT3	PAQR7	psi-mi:“MI:0915”(physical association)	0.490
PAQR7	STAT3	psi-mi:“MI:0915”(physical association)	0.490
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
SPPL2B	HAS3	psi-mi:“MI:0914”(association)	0.350
LPAR2	EI24	psi-mi:“MI:0914”(association)	0.350
PAQR7	FAM209A	psi-mi:“MI:0915”(physical association)	0.000
PAQR7	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): PAQR7 (Two-hybrid), PAQR7 (Two-hybrid), PAQR7 (Two-hybrid), PAQR7 (Affinity Capture-RNA), PAQR7 (Affinity Capture-MS), PAQR7 (Affinity Capture-MS), PAQR7 (Affinity Capture-MS), RPL6 (Cross-Linking-MS (XL-MS)), PAQR7 (Affinity Capture-RNA)

ESM2 similar proteins: A4IFN5, A6NDV4, B1AWJ5, B1AZA5, B2LYG4, P59266, Q05B45, Q0VCJ8, Q3KRC4, Q3UMZ3, Q5EA70, Q5H8A4, Q5QJU3, Q5RBJ7, Q5U3C3, Q5VTY9, Q5ZMH6, Q6PHN7, Q6TCH4, Q6W5G4, Q6ZVK1, Q7Z7J7, Q865K8, Q86WK9, Q8BHH9, Q8BMT9, Q8BWB6, Q8C1E7, Q8K3J9, Q8N6M3, Q8NBT3, Q8NEB5, Q8NFT2, Q8VCW4, Q8VCY8, Q8VD53, Q8VDI9, Q96GM1, Q9BSA9, Q9BXJ8

Diamond homologs: Q6DC77, Q6ETK9, Q6TCG2, Q6TCG5, Q6TCH4, Q6ZVX9, Q7ZVH1, Q801D8, Q801G2, Q80ZE4, Q80ZE5, Q84N34, Q865K8, Q865K9, Q86WK9, Q8N4S7, Q8TEZ7, Q9DCU0, Q9JJE4, Q9NXK6, Q9SVF3, Q9SZG0, Q753H5, Q10PI5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

52 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

419 predictions. Top by Δscore:

Variant	Effect	Δscore
1:25863859:GAG:G	acceptor_gain	1.0000
1:25863862:C:CC	acceptor_gain	1.0000
1:25863857:GGGAG:G	acceptor_gain	0.9900
1:25863858:GGAG:G	acceptor_gain	0.9900
1:25863860:AG:A	acceptor_gain	0.9900
1:25863858:GGAGC:G	acceptor_gain	0.9800
1:25863859:GAGC:G	acceptor_gain	0.9800
1:25863860:AGC:A	acceptor_gain	0.9800
1:25863861:GCT:G	acceptor_gain	0.9800
1:25863862:C:CA	acceptor_gain	0.9800
1:25863863:T:A	acceptor_gain	0.9800
1:25865904:TGA:T	donor_gain	0.9700
1:25863875:C:CT	acceptor_gain	0.9400
1:25870725:T:TC	acceptor_gain	0.8900
1:25870725:T:C	acceptor_gain	0.8800
1:25863875:C:T	acceptor_gain	0.8700
1:25870701:A:T	acceptor_gain	0.8700
1:25865898:A:AC	donor_gain	0.8400
1:25865903:T:C	donor_gain	0.8100
1:25870699:TCA:T	acceptor_gain	0.8100
1:25870710:C:CT	acceptor_gain	0.8100
1:25863876:A:T	acceptor_gain	0.7700
1:25868020:C:A	donor_gain	0.7700
1:25865901:A:AC	donor_gain	0.7600
1:25865902:C:CC	donor_gain	0.7600
1:25870711:A:T	acceptor_gain	0.7600
1:25870702:G:GC	acceptor_gain	0.7500
1:25865859:G:A	donor_gain	0.7400
1:25870702:G:C	acceptor_gain	0.7300
1:25865878:C:CA	donor_gain	0.7100

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000344681 (1:25869069 G>A), RS1000460195 (1:25864888 G>A), RS1000522918 (1:25876850 AGGAAAG>A), RS1000577264 (1:25875586 G>A), RS1000674681 (1:25870660 G>A), RS1000707192 (1:25871156 G>A), RS1000759207 (1:25863755 G>A,C), RS1000777831 (1:25869369 C>T), RS1000812143 (1:25872201 T>C,G), RS1000889742 (1:25864683 T>C,G), RS1000977752 (1:25877369 T>G), RS1001008567 (1:25870248 G>A), RS1001129327 (1:25874400 T>C), RS1001158974 (1:25874654 G>A), RS1001389932 (1:25868221 A>G)

Disease associations

OMIM: gene MIM:607779 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Mifepristone	decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.