PAQR9

Summary

PAQR9 (progestin and adipoQ receptor family member 9, HGNC:30131) is a protein-coding gene on chromosome 3q23, encoding Membrane progestin receptor epsilon (Q6ZVX9). Plasma membrane progesterone (P4) receptor coupled to G proteins.

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

Source: NCBI Gene 344838 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_198504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30131
Approved symbol	PAQR9
Name	progestin and adipoQ receptor family member 9
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ41938, BLNC1
Ensembl gene	ENSG00000188582
Ensembl biotype	protein_coding
OMIM	614580
Entrez	344838

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000340634, ENST00000492509, ENST00000498470, ENST00000900185, ENST00000900186

RefSeq mRNA: 3 — MANE Select: NM_198504 NM_001375300, NM_001375301, NM_198504

CCDS: CCDS3128

Canonical transcript exons

ENST00000340634 — 1 exons

Exon	Start	End
ENSE00001372540	142954585	142963674

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 89.40.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4717 / max 55.5292, expressed in 197 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44871	0.2003	90
44873	0.1984	89
44872	0.0730	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	89.40	gold quality
liver	UBERON:0002107	79.79	gold quality
right lobe of liver	UBERON:0001114	79.17	gold quality
right testis	UBERON:0004534	78.30	gold quality
left testis	UBERON:0004533	78.16	gold quality
testis	UBERON:0000473	76.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.82	silver quality
pigmented layer of retina	UBERON:0001782	75.14	gold quality
biceps brachii	UBERON:0001507	73.47	gold quality
heart left ventricle	UBERON:0002084	73.13	gold quality
cardiac ventricle	UBERON:0002082	72.90	gold quality
myocardium	UBERON:0002349	72.44	gold quality
trabecular bone tissue	UBERON:0002483	72.40	gold quality
apex of heart	UBERON:0002098	71.32	gold quality
heart right ventricle	UBERON:0002080	70.62	gold quality
adrenal tissue	UBERON:0018303	69.84	gold quality
prefrontal cortex	UBERON:0000451	68.48	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	68.33	silver quality
endothelial cell	CL:0000115	68.30	gold quality
bone marrow	UBERON:0002371	67.62	gold quality
right atrium auricular region	UBERON:0006631	67.49	gold quality
cardiac atrium	UBERON:0002081	67.28	gold quality
heart	UBERON:0000948	66.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.27	gold quality
primary visual cortex	UBERON:0002436	64.14	gold quality
skeletal muscle tissue	UBERON:0001134	63.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	63.44	gold quality
cortical plate	UBERON:0005343	63.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.52	silver quality
bone marrow cell	CL:0002092	62.39	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting PAQR9, 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-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-548C-3P	99.99	74.01	7587
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-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-128-3P	99.95	71.17	2484

Literature-anchored findings (GeneRIF, showing 4)

• PAQR9 is a previously uncharacterized PAQR which is also capable of responding to progesterone. (PMID:18603275)
• The results suggest that PAQR6 and PAQR9 (mPRdelta and mPRepsilon) function as mPRs coupled to G proteins and are potential intermediaries of nonclassical antiapoptotic actions of neurosteroids in the central nervous system. (PMID:23161870)
• the polyubiquitination of MLPs is enhanced by PAQR9 PAQR9 binds to the DUF3538 domain within the proline-rich stretch of BAG6. PAQR9 reduces the binding of MLPs to BAG6 in a DUF3538 domain-dependent manner. Taken together, our results indicate that PAQR9 plays a role in the regulation of protein quality control of MLPs via affecting the interaction of BAG6 with membrane proteins. (PMID:31904842)
• PAQR9 regulates hepatic ketogenesis and fatty acid oxidation during fasting by modulating protein stability of PPARalpha. (PMID:34474167)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	paqr9	ENSDARG00000052059
mus_musculus	Paqr9	ENSMUSG00000064225
rattus_norvegicus	Paqr9	ENSRNOG00000085801

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD (ENSG00000108960), MMD2 (ENSG00000136297), PAQR5 (ENSG00000137819), ADIPOR1 (ENSG00000159346), PAQR6 (ENSG00000160781), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749)

Protein

Protein identifiers

Membrane progestin receptor epsilon — Q6ZVX9 (reviewed: Q6ZVX9)

Alternative names: Membrane progesterone P4 receptor epsilon, Membrane progesterone receptor epsilon, Progesterone and adipoQ receptor family member 9, Progestin and adipoQ receptor family member 9, Progestin and adipoQ receptor family member IX

All UniProt accessions (3): Q6ZVX9, H7C4R3, H7C5S8

UniProt curated annotations — full annotation on UniProt →

Function. Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(s) mediated pathway. May be involved in regulating rapid P4 signaling in the nervous system. Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Tissue specificity. Expression levels vary widely in a range of tissues. Expressed in the brain, at high level in the pituitary gland and also in hypothalamus, limbic system, caudate nucleus accumens, pons and olfactory bulb.

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 (3): NP_001362229, NP_001362230, NP_940906* (*=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, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZVX9-F1	86.63	0.73

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, AREB6_01, FOXO4_01, GTGCCTT_MIR506, HFH4_01, HNF1_01, ACEVEDO_LIVER_CANCER_UP, FOXO4_02, FOX_Q2, TAATTA_CHX10_01, GOMF_STEROID_BINDING, GOMF_LIPID_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3

GO Biological Process (0):

GO Molecular Function (4): steroid binding (GO:0005496), signaling receptor activity (GO:0038023), 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
lipid binding	1
molecular transducer activity	1
binding	1
cation binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAQR9	PAQR6	Q6TCH4	916
PAQR9	PGRMC1	O00264	641
PAQR9	PGRMC2	O15173	607
PAQR9	PAQR4	Q8N4S7	574
PAQR9	ZNF507	Q8TCN5	538
PAQR9	CYB5D2	Q8WUJ1	535
PAQR9	NENF	Q9UMX5	502
PAQR9	PAQR5	Q9NXK6	484
PAQR9	PAQR3	Q6TCH7	467
PAQR9	INTS5	Q6P9B9	445
PAQR9	ZSCAN30	Q86W11	445
PAQR9	DNAJC11	Q9NVH1	440
PAQR9	RNF152	Q8N8N0	433
PAQR9	GET4	Q7L5D6	430
PAQR9	MMD	Q15546	400
PAQR9	GPR152	Q8TDT2	400

IntAct

0 interactions, top by confidence:

BioGRID (14): HUWE1 (Affinity Capture-MS), UBQLN2 (Affinity Capture-MS), UBQLN1 (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS), NPEPPS (Affinity Capture-MS), BAG6 (Affinity Capture-MS), PAQR9 (Affinity Capture-MS), PAQR9 (Affinity Capture-Western), BAG6 (Affinity Capture-Western), CANX (Co-localization), PAQR9 (Affinity Capture-Western), PPARA (Affinity Capture-Western), HUWE1 (Affinity Capture-Western)

ESM2 similar proteins: A2A559, A2V7M9, A7YWP2, A8WFS8, B7F9G7, B9F6Z0, O57328, O70421, P18537, Q08463, Q08464, Q09749, Q0VFE3, Q10LN5, Q10Q65, Q24760, Q5JMH0, Q5N808, Q5Z653, Q651J5, Q652J4, Q657S5, Q67VS5, Q69P80, Q6DC77, Q6ETK9, Q6K991, Q6L8F7, Q6L8F9, Q6TCG2, Q6ZVX9, Q753H5, Q801D8, Q801G2, Q80ZE5, Q84N34, Q865K9, Q86V24, Q8BQS5, Q8IWX5

Diamond homologs: Q6DC77, Q6TCG2, Q6TCG5, Q6TCH4, Q6ZVX9, Q7ZVH1, Q801D8, Q80ZE5, Q865K9, Q8TEZ7, Q9DCU0, Q9NXK6, A8WZU4, B7F9G7, Q09749, Q09910, Q10PI5, Q12442, Q6ETK9, Q6TCG8, Q6TCH7, Q753H5, Q84N34, Q86V24, Q8BQS5, Q8N4S7, Q91VH1, Q93ZH9, Q94177, Q96A54, Q9SVF3, Q9SZG0, Q9VCY8, Q9ZUH8, Q801G2, Q80ZE4, Q865K8, Q86WK9, Q9JJE4, Q07959

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	29
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

40 predictions. Top by Δscore:

Variant	Effect	Δscore
3:142963580:T:TA	donor_gain	0.9600
3:142963597:C:CT	donor_gain	0.8700
3:142963598:T:TT	donor_gain	0.8700
3:142963595:TGC:T	donor_gain	0.7500
3:142963596:G:GC	donor_gain	0.4900
3:142963574:G:C	donor_gain	0.4300
3:142963646:A:AC	donor_gain	0.4300
3:142963647:C:CC	donor_gain	0.4300
3:142963493:CT:C	acceptor_loss	0.4200
3:142963494:T:A	acceptor_loss	0.4200
3:142963488:CGCTC:C	acceptor_gain	0.4100
3:142963493:C:CC	acceptor_gain	0.4100
3:142963592:CCCTG:C	donor_gain	0.4000
3:142963593:CCTGC:C	donor_gain	0.4000
3:142963490:CTC:C	acceptor_gain	0.3800
3:142963602:G:T	donor_gain	0.3800
3:142963504:A:C	acceptor_loss	0.3700
3:142963491:TC:T	acceptor_gain	0.3300
3:142963492:CC:C	acceptor_gain	0.3300
3:142963500:T:C	acceptor_gain	0.3300
3:142963594:CTGC:C	donor_gain	0.3300
3:142963495:A:C	acceptor_loss	0.3200
3:142963601:C:CT	donor_gain	0.3100
3:142963489:GCTC:G	acceptor_gain	0.3000
3:142963490:CTCC:C	acceptor_gain	0.3000
3:142963491:TCCT:T	acceptor_gain	0.3000
3:142963499:A:C	acceptor_gain	0.3000
3:142963500:T:TC	acceptor_gain	0.3000
3:142963581:C:A	donor_gain	0.3000
3:142963589:AGCC:A	donor_gain	0.3000

AlphaMissense

2439 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:142962392:G:C	H315Q	1.000
3:142962392:G:T	H315Q	1.000
3:142962394:G:C	H315D	1.000
3:142962404:G:C	H311Q	1.000
3:142962404:G:T	H311Q	1.000
3:142962406:G:C	H311D	1.000
3:142962408:C:A	S310I	1.000
3:142962414:C:T	G308D	1.000
3:142962423:T:A	D305V	1.000
3:142962450:G:T	P296H	1.000
3:142962851:G:C	S162R	1.000
3:142962851:G:T	S162R	1.000
3:142962853:T:G	S162R	1.000
3:142962866:G:C	D157E	1.000
3:142962866:G:T	D157E	1.000
3:142962867:T:A	D157V	1.000
3:142962867:T:G	D157A	1.000
3:142962868:C:G	D157H	1.000
3:142962917:G:C	H140Q	1.000
3:142962917:G:T	H140Q	1.000
3:142963075:A:G	W88R	1.000
3:142963075:A:T	W88R	1.000
3:142963079:G:C	N86K	1.000
3:142963079:G:T	N86K	1.000
3:142963089:T:A	E83V	1.000
3:142962374:G:C	S321R	0.999
3:142962374:G:T	S321R	0.999
3:142962376:T:G	S321R	0.999
3:142962393:T:C	H315R	0.999
3:142962394:G:A	H315Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000256851 (3:142956368 G>A), RS1000569541 (3:142964025 G>C,T), RS1000636037 (3:142963333 G>A,T), RS1000891850 (3:142949686 G>A,C), RS1000930479 (3:142964412 C>G,T), RS1001161828 (3:142951528 G>A), RS1001258073 (3:142964175 G>A,C,T), RS1002108539 (3:142965014 G>A), RS1002268280 (3:142957504 A>T), RS1002422136 (3:142964847 G>A), RS1002429086 (3:142953015 G>A), RS1002528917 (3:142958866 A>G), RS1002601974 (3:142957241 C>G), RS1002759228 (3:142966007 T>A,C), RS1002794289 (3:142954320 A>G)

Disease associations

OMIM: gene MIM:614580 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001414_18	Phospholipid levels (plasma)	6.000000e-29
GCST008931_1	Phosphatidylinositol levels	3.000000e-08
GCST010173_158	Triglyceride levels	4.000000e-08
GCST010243_117	Apolipoprotein B levels	9.000000e-12
GCST010244_156	Triglyceride levels	2.000000e-11
GCST010245_57	LDL cholesterol levels	2.000000e-11
GCST90002404_60	Red cell distribution width	5.000000e-15
GCST90011898_151	Alanine aminotransferase levels	3.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation, affects cotreatment, decreases expression	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Tetrachlorodibenzodioxin	decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NSC668394	increases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Azathioprine	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Quercetin	decreases expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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