PAQR5

Summary

PAQR5 (progestin and adipoQ receptor family member 5, HGNC:29645) is a protein-coding gene on chromosome 15q23, encoding Membrane progestin receptor gamma (Q9NXK6). Plasma membrane progesterone (P4) receptor coupled to G proteins.

Predicted to enable signaling receptor activity. Predicted to be involved in oogenesis. Predicted to be located in plasma membrane.

Source: NCBI Gene 54852 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_017705

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29645
Approved symbol	PAQR5
Name	progestin and adipoQ receptor family member 5
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20190, MPRG
Ensembl gene	ENSG00000137819
Ensembl biotype	protein_coding
OMIM	607781
Entrez	54852

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000340965, ENST00000395407, ENST00000558684, ENST00000561027, ENST00000561153, ENST00000561250, ENST00000909132, ENST00000909133, ENST00000909134, ENST00000909135, ENST00000909136, ENST00000934600, ENST00000959805

RefSeq mRNA: 2 — MANE Select: NM_017705 NM_001104554, NM_017705

CCDS: CCDS10232

Canonical transcript exons

ENST00000395407 — 9 exons

Exon	Start	End
ENSE00000696441	69399974	69400115
ENSE00000696444	69397468	69397564
ENSE00000931697	69389654	69389780
ENSE00001521630	69403581	69407780
ENSE00001521631	69298912	69299056
ENSE00001521649	69359966	69360131
ENSE00001521651	69337341	69337501
ENSE00003498278	69384677	69384882
ENSE00003621044	69379883	69380010

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 88.39.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7608 / max 121.3506, expressed in 826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147442	2.7426	824
147443	0.0182	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	88.39	gold quality
rectum	UBERON:0001052	86.21	gold quality
right adrenal gland	UBERON:0001233	86.15	gold quality
left adrenal gland cortex	UBERON:0035825	85.89	gold quality
left adrenal gland	UBERON:0001234	85.86	gold quality
right adrenal gland cortex	UBERON:0035827	85.73	gold quality
mucosa of transverse colon	UBERON:0004991	85.61	gold quality
lower esophagus mucosa	UBERON:0035834	84.40	gold quality
adult mammalian kidney	UBERON:0000082	83.61	gold quality
adrenal gland	UBERON:0002369	83.15	gold quality
adrenal cortex	UBERON:0001235	82.69	gold quality
islet of Langerhans	UBERON:0000006	80.02	gold quality
adrenal tissue	UBERON:0018303	79.73	gold quality
esophagus mucosa	UBERON:0002469	79.38	gold quality
colonic epithelium	UBERON:0000397	78.54	gold quality
transverse colon	UBERON:0001157	78.07	gold quality
kidney	UBERON:0002113	77.79	gold quality
cortex of kidney	UBERON:0001225	76.49	gold quality
pancreas	UBERON:0001264	75.29	gold quality
body of pancreas	UBERON:0001150	75.15	gold quality
upper lobe of left lung	UBERON:0008952	73.98	gold quality
right lung	UBERON:0002167	73.37	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.27	silver quality
upper lobe of lung	UBERON:0008948	72.42	gold quality
metanephros	UBERON:0000081	71.07	gold quality
nephron tubule	UBERON:0001231	70.90	silver quality
body of stomach	UBERON:0001161	70.53	gold quality
colonic mucosa	UBERON:0000317	70.08	gold quality
skin of abdomen	UBERON:0001416	70.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	69.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

133 targeting PAQR5, 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-4776-3P	100.00	68.73	1340
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893

Literature-anchored findings (GeneRIF, showing 3)

• Heterologous expression of MPRG in yeast confirms its ability to function as a membrane progesterone receptor. (PMID:18603275)
• 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)
• PAQR5 inhibits the growth and metastasis of clear cell renal cell carcinoma by suppressing the JAK/STAT3 signaling pathway. (PMID:37126128)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	paqr5a	ENSDARG00000041145
danio_rerio	paqr5b	ENSDARG00000052688
mus_musculus	Paqr5	ENSMUSG00000032278
rattus_norvegicus	Paqr5	ENSRNOG00000014164
drosophila_melanogaster	AdipoR	FBGN0038984
caenorhabditis_elegans		WBGENE00016610
caenorhabditis_elegans		WBGENE00019643

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD (ENSG00000108960), MMD2 (ENSG00000136297), ADIPOR1 (ENSG00000159346), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Membrane progestin receptor gamma — Q9NXK6 (reviewed: Q9NXK6)

Alternative names: Membrane progesterone P4 receptor gamma, Membrane progesterone receptor gamma, Progesterone and adipoQ receptor family member 5, Progestin and adipoQ receptor family member 5, Progestin and adipoQ receptor family member V

All UniProt accessions (2): Q9NXK6, H0YL06

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.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the brain, lung, kidney, colon, adrenal and lung.

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 (2): NP_001098024, NP_060175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family

Pfam: PF03006

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXK6-F1	92.54	0.85

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 103 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, MODULE_255, AREB6_03, GOBP_OOGENESIS, MODULE_317, KOYAMA_SEMA3B_TARGETS_UP, LIAO_METASTASIS, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, BIOCARTA_MPR_PATHWAY, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, chr15q23, RIGGI_EWING_SARCOMA_PROGENITOR_UP, RICKMAN_HEAD_AND_NECK_CANCER_C, TGGAAA_NFAT_Q4_01

GO Biological Process (2): oogenesis (GO:0048477), cell differentiation (GO:0030154)

GO Molecular Function (5): steroid binding (GO:0005496), signaling receptor activity (GO:0038023), protein binding (GO:0005515), lipid binding (GO:0008289), metal ion binding (GO:0046872)

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
cellular developmental process	1
lipid binding	1
molecular transducer activity	1
cation binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAQR5	PGRMC2	O15173	809
PAQR5	PGRMC1	O00264	783
PAQR5	CYB5D2	Q8WUJ1	609
PAQR5	PGR	P06401	532
PAQR5	NENF	Q9UMX5	532
PAQR5	PAQR7	Q86WK9	531
PAQR5	PAQR8	Q8TEZ7	530
PAQR5	PAQR9	Q6ZVX9	484
PAQR5	MMD	Q15546	474
PAQR5	GINM1	Q9NU53	439
PAQR5	GPR137C	Q8N3F9	411
PAQR5	MMD2	Q8IY49	392
PAQR5	SERBP1	Q8NC51	383
PAQR5	CYB5B	O43169	379
PAQR5	GPR157	Q5UAW9	377

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PAQR5	PHYHIP	psi-mi:“MI:0915”(physical association)	0.590
PAQR5	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
SGPL1	PAQR5	psi-mi:“MI:0915”(physical association)	0.560
PAQR5	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
IL3RA	PAQR5	psi-mi:“MI:0915”(physical association)	0.560
PAQR5	IGSF9	psi-mi:“MI:0915”(physical association)	0.560
GPX8	PAQR5	psi-mi:“MI:0915”(physical association)	0.560
PAQR5	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
	NBAS	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
PAQR5	IL3RA	psi-mi:“MI:0915”(physical association)	0.000
PAQR5	IGSF9	psi-mi:“MI:0915”(physical association)	0.000
PAQR5	GPX8	psi-mi:“MI:0915”(physical association)	0.000
PAQR5	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): SYNE4 (Two-hybrid), PHYHIP (Affinity Capture-MS), PHYHIP (Affinity Capture-MS), PAQR5 (Two-hybrid), PAQR5 (Affinity Capture-RNA), PAQR5 (Two-hybrid), PAQR5 (Two-hybrid), GPX8 (Two-hybrid), SGPL1 (Two-hybrid), IL3RA (Two-hybrid), PAQR5 (Affinity Capture-MS), PHYHIP (Affinity Capture-MS)

ESM2 similar proteins: A1L272, A4FUY9, A5D7C9, A5PN43, A9JSP6, B5DFH9, B9EJG8, D3ZEH5, E1BY51, E2RFJ3, O19133, O70578, P19518, P35575, P51811, P97707, Q19KA1, Q28BP2, Q29RU6, Q49LS5, Q569T7, Q5F383, Q5GH61, Q5TF39, Q5ZKY0, Q6GPL4, Q6GQE1, Q6P0C6, Q7SYC7, Q80UF9, Q86TG1, Q86X19, Q8BMD6, Q8C8S3, Q8CIF6, Q8CJ61, Q8IZ96, Q8NBJ9, Q8R000, Q8TCT6

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2759 predictions. Top by Δscore:

Variant	Effect	Δscore
15:69331929:AAGT:A	acceptor_gain	1.0000
15:69331930:A:G	acceptor_gain	1.0000
15:69389776:TCCAG:T	donor_loss	1.0000
15:69389777:CCAGG:C	donor_loss	1.0000
15:69389778:CAG:C	donor_loss	1.0000
15:69389779:AGG:A	donor_loss	1.0000
15:69389780:GGTA:G	donor_loss	1.0000
15:69389781:GT:G	donor_loss	1.0000
15:69389782:T:A	donor_loss	1.0000
15:69403666:G:GT	donor_gain	1.0000
15:69299053:CCAG:C	donor_loss	0.9900
15:69299054:CAG:C	donor_loss	0.9900
15:69299057:GT:G	donor_loss	0.9900
15:69299058:T:A	donor_loss	0.9900
15:69331929:A:AG	acceptor_gain	0.9900
15:69331929:AAGTG:A	acceptor_gain	0.9900
15:69337335:TCACA:T	acceptor_loss	0.9900
15:69337336:CACAG:C	acceptor_loss	0.9900
15:69337338:CAGG:C	acceptor_loss	0.9900
15:69337339:A:AC	acceptor_loss	0.9900
15:69337340:G:C	acceptor_loss	0.9900
15:69337499:GTG:G	donor_gain	0.9900
15:69357080:T:TA	acceptor_gain	0.9900
15:69357086:T:A	acceptor_gain	0.9900
15:69359423:G:GG	donor_gain	0.9900
15:69380065:G:GT	donor_gain	0.9900
15:69380095:GGC:G	donor_gain	0.9900
15:69397563:GG:G	donor_gain	0.9900
15:69397564:GG:G	donor_gain	0.9900
15:69399966:A:AG	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000059095 (15:69324874 C>T), RS1000065739 (15:69311457 A>G), RS1000068032 (15:69365398 G>A,T), RS1000105790 (15:69394153 ACCT>A), RS1000165058 (15:69333870 A>G), RS1000180101 (15:69351114 A>C), RS1000227442 (15:69378305 T>G), RS1000234332 (15:69387996 G>A), RS1000237355 (15:69305679 C>T), RS1000238156 (15:69344695 T>C), RS1000250253 (15:69342744 G>T), RS1000265560 (15:69388335 C>A,G), RS1000278946 (15:69386020 C>T), RS1000322928 (15:69342390 G>A,T), RS1000341668 (15:69372229 A>T)

Disease associations

OMIM: gene MIM:607781 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005982_9	Calcium levels	4.000000e-09
GCST007094_150	Diastolic blood pressure	2.000000e-08
GCST007267_146	Systolic blood pressure	5.000000e-08
GCST90002379_69	Basophil count	1.000000e-12
GCST90002380_32	Basophil percentage of white cells	1.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	9
Benzo(a)pyrene	increases expression, increases methylation	4
Air Pollutants	increases expression, increases abundance, decreases expression	3
Cyclosporine	increases expression	3
sodium arsenite	affects methylation, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Calcitriol	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
cupric chloride	increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Azathioprine	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1ZY	Abcam HeLa PAQR5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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