PAQR6

Summary

PAQR6 (progestin and adipoQ receptor family member 6, HGNC:30132) is a protein-coding gene on chromosome 1q22, encoding Membrane progestin receptor delta (Q6TCH4). 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 79957 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_198406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30132
Approved symbol	PAQR6
Name	progestin and adipoQ receptor family member 6
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22672, PRdelta
Ensembl gene	ENSG00000160781
Ensembl biotype	protein_coding
OMIM	614579
Entrez	79957

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000292291, ENST00000335852, ENST00000340183, ENST00000356983, ENST00000368270, ENST00000468632, ENST00000470198, ENST00000475507, ENST00000480773, ENST00000491107, ENST00000492619, ENST00000540423, ENST00000612424, ENST00000613336, ENST00000623241, ENST00000649236, ENST00000649372, ENST00000652405, ENST00000882649, ENST00000882650, ENST00000882651, ENST00000882652, ENST00000882653, ENST00000882654, ENST00000955080

RefSeq mRNA: 12 — MANE Select: NM_198406 NM_001272104, NM_001272105, NM_001272106, NM_001272107, NM_001272108, NM_001272109, NM_001272110, NM_001272111, NM_001272112, NM_001272113, NM_024897, NM_198406

CCDS: CCDS1135, CCDS1136, CCDS60301, CCDS72945, CCDS72946

Canonical transcript exons

ENST00000292291 — 8 exons

Exon	Start	End
ENSE00003487254	156247957	156248056
ENSE00003535355	156246123	156246250
ENSE00003547370	156243320	156244403
ENSE00003568826	156246681	156246756
ENSE00003619400	156245142	156245238
ENSE00003652181	156245535	156245661
ENSE00003716919	156245782	156245987
ENSE00003720666	156244761	156244911

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 99.90.

FANTOM5 (CAGE): breadth broad, TPM avg 22.1139 / max 4070.1317, expressed in 208 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15093	18.7919	156
15091	1.8885	96
15094	0.4908	80
15090	0.4534	81
15088	0.2607	109
201754	0.1474	69
15092	0.0580	39
15095	0.0232	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.90	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.84	gold quality
inferior olivary complex	UBERON:0002127	99.79	gold quality
spinal cord	UBERON:0002240	99.79	gold quality
cranial nerve II	UBERON:0000941	99.49	gold quality
medial globus pallidus	UBERON:0002477	99.43	gold quality
substantia nigra	UBERON:0002038	99.34	gold quality
midbrain	UBERON:0001891	99.24	gold quality
hypothalamus	UBERON:0001898	99.10	gold quality
globus pallidus	UBERON:0001875	99.05	gold quality
inferior vagus X ganglion	UBERON:0005363	99.05	gold quality
amygdala	UBERON:0001876	99.02	gold quality
medulla oblongata	UBERON:0001896	98.80	gold quality
cingulate cortex	UBERON:0003027	98.67	gold quality
anterior cingulate cortex	UBERON:0009835	98.67	gold quality
subthalamic nucleus	UBERON:0001906	98.64	gold quality
putamen	UBERON:0001874	98.57	gold quality
nucleus accumbens	UBERON:0001882	98.53	gold quality
caudate nucleus	UBERON:0001873	98.49	gold quality
right frontal lobe	UBERON:0002810	98.44	gold quality
ventral tegmental area	UBERON:0002691	98.41	gold quality
pons	UBERON:0000988	98.29	gold quality
superior vestibular nucleus	UBERON:0007227	98.13	gold quality
Ammon’s horn	UBERON:0001954	98.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.69	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.65	gold quality
postcentral gyrus	UBERON:0002581	97.48	gold quality
prefrontal cortex	UBERON:0000451	97.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting PAQR6, 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-6508-5P	99.92	70.67	2465
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-3135A	96.41	65.30	494
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-6514-5P	95.07	66.02	655
HSA-MIR-4640-3P	94.58	63.02	263

Literature-anchored findings (GeneRIF, showing 3)

• PAQR6 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)
• PAQR6 Upregulation Is Associated with AR Signaling and Unfavorite Prognosis in Prostate Cancers. (PMID:34572596)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	paqr6	ENSDARG00000041483
mus_musculus	Paqr6	ENSMUSG00000041423
rattus_norvegicus	Paqr6	ENSRNOG00000026059
drosophila_melanogaster	AdipoR	FBGN0038984
caenorhabditis_elegans		WBGENE00016610
caenorhabditis_elegans		WBGENE00019643

Paralogs (10): ADIPOR2 (ENSG00000006831), MMD (ENSG00000108960), MMD2 (ENSG00000136297), PAQR5 (ENSG00000137819), ADIPOR1 (ENSG00000159346), PAQR4 (ENSG00000162073), PAQR3 (ENSG00000163291), PAQR8 (ENSG00000170915), PAQR7 (ENSG00000182749), PAQR9 (ENSG00000188582)

Protein

Protein identifiers

Membrane progestin receptor delta — Q6TCH4 (reviewed: Q6TCH4)

Alternative names: Membrane progesterone P4 receptor delta, Membrane progesterone receptor delta, Progesterone and adipoQ receptor family member 6, Progestin and adipoQ receptor family member 6

All UniProt accessions (8): Q6TCH4, A0A494C0R3, A0A494C1I0, B4DJ42, Q5TCK5, Q5TCK7, Q5TCK8, Q7Z4Q8

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. Involved in neurosteroid inhibition of apoptosis. 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. Brain specific. Highly expressed in the hypothalamus, also expressed in forebrain, amygdala, corpus callosum and spinal cord.

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.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6TCH4-1	1	yes
Q6TCH4-2	2
Q6TCH4-3	3
Q6TCH4-4	4
Q6TCH4-5	5

RefSeq proteins (12): NP_001259033, NP_001259034, NP_001259035, NP_001259036, NP_001259037, NP_001259038, NP_001259039, NP_001259040, NP_001259041, NP_001259042, NP_079173, NP_940798* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004254	AdipoR/HlyIII-related	Family

Pfam: PF03006

UniProt features (25 total): topological domain 8, transmembrane region 7, splice variant 4, sequence conflict 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6TCH4-F1	91.23	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): MYAATNNNNNNNGGC_UNKNOWN, ROZANOV_MMP14_TARGETS_UP, chr1q22, LEIN_CEREBELLUM_MARKERS, WGGAATGY_TEF1_Q6, ZHAN_MULTIPLE_MYELOMA_CD2_DN, GOMF_STEROID_BINDING, GOMF_LIPID_BINDING, EPPERT_LSC_R, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_UP, MTF1_Q4, FORTSCHEGGER_PHF8_TARGETS_DN, PRC2_SUZ12_UP.V1_UP, IL21_UP.V1_UP

GO Biological Process (0):

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

Protein interactions and networks

STRING

644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAQR6	PAQR9	Q6ZVX9	916
PAQR6	PAQR7	Q86WK9	816
PAQR6	PGRMC1	O00264	695
PAQR6	PGRMC2	O15173	670
PAQR6	CYB5D2	Q8WUJ1	605
PAQR6	NENF	Q9UMX5	531
PAQR6	PAQR3	Q6TCH7	437
PAQR6	PAQR4	Q8N4S7	419
PAQR6	PGR	P06401	413
PAQR6	PAQR8	Q8TEZ7	389
PAQR6	CYB5B	O43169	384
PAQR6	CYB5A	P00167	377
PAQR6	ADIPOR1	Q96A54	370
PAQR6	ADIPOR2	Q86V24	365
PAQR6	C2CD4D	B7Z1M9	364

IntAct

19 interactions, top by confidence:

A	B	Type	Score
RNF144A	PAQR6	psi-mi:“MI:0915”(physical association)	0.560
PAQR6	GPX8	psi-mi:“MI:0915”(physical association)	0.560
MUC1	PAQR6	psi-mi:“MI:0915”(physical association)	0.560
PAQR6	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
GLP1R	PAQR6	psi-mi:“MI:0915”(physical association)	0.540
PAQR6	GLP1R	psi-mi:“MI:0915”(physical association)	0.540
PAQR6	GLP1R	psi-mi:“MI:0403”(colocalization)	0.540
PAQR6	CCR8	psi-mi:“MI:0915”(physical association)	0.370
PAQR6	DRD2	psi-mi:“MI:0915”(physical association)	0.370
PAQR6	RNF144A	psi-mi:“MI:0915”(physical association)	0.000
PAQR6	GPX8	psi-mi:“MI:0915”(physical association)	0.000
PAQR6	MUC1	psi-mi:“MI:0915”(physical association)	0.000
PAQR6	CREB3L1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): PAQR6 (Affinity Capture-RNA), PAQR6 (Two-hybrid), PAQR6 (Two-hybrid), GPX8 (Two-hybrid), MUC1 (Two-hybrid), PAQR6 (Two-hybrid), PAQR6 (Two-hybrid), PAQR6 (Protein-peptide), PAQR6 (PCA), PAQR6 (Affinity Capture-Western)

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, 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, Q03419

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1305 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156245239:C:CC	acceptor_gain	1.0000
1:156246248:CAC:C	acceptor_gain	1.0000
1:156246251:CTAG:C	acceptor_loss	1.0000
1:156246252:T:C	acceptor_loss	1.0000
1:156246259:G:C	acceptor_gain	1.0000
1:156247950:T:TA	donor_gain	1.0000
1:156244404:C:CC	acceptor_gain	0.9900
1:156245247:C:CT	acceptor_gain	0.9900
1:156245777:CTCA:C	donor_loss	0.9900
1:156245780:A:AC	donor_gain	0.9900
1:156245780:AC:A	donor_gain	0.9900
1:156245781:C:CA	donor_loss	0.9900
1:156245781:C:CC	donor_gain	0.9900
1:156245781:CC:C	donor_gain	0.9900
1:156246116:C:A	donor_gain	0.9900
1:156246247:ACAC:A	acceptor_gain	0.9900
1:156246248:CACC:C	acceptor_gain	0.9900
1:156246249:AC:A	acceptor_gain	0.9900
1:156246250:CC:C	acceptor_gain	0.9900
1:156246251:C:CC	acceptor_gain	0.9900
1:156246256:G:C	acceptor_gain	0.9900
1:156246256:G:GC	acceptor_gain	0.9900
1:156247955:A:AC	donor_gain	0.9900
1:156247955:AC:A	donor_gain	0.9900
1:156247956:C:CC	donor_gain	0.9900
1:156247956:CC:C	donor_gain	0.9900
1:156244907:CCGAG:C	acceptor_gain	0.9800
1:156244908:CGAGC:C	acceptor_gain	0.9800
1:156245136:CCTTA:C	donor_loss	0.9800
1:156245137:CTT:C	donor_loss	0.9800

AlphaMissense

2214 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156245795:G:C	S124R	0.996
1:156245795:G:T	S124R	0.996
1:156245797:T:G	S124R	0.996
1:156246149:G:C	N51K	0.996
1:156246149:G:T	N51K	0.996
1:156244397:C:A	S256I	0.995
1:156244396:G:C	S256R	0.994
1:156244396:G:T	S256R	0.994
1:156244398:T:G	S256R	0.994
1:156246145:A:G	W53R	0.994
1:156246145:A:T	W53R	0.994
1:156246159:T:A	E48V	0.993
1:156244383:G:C	H261D	0.992
1:156244771:A:C	F250L	0.992
1:156244771:A:T	F250L	0.992
1:156244773:A:G	F250L	0.992
1:156245184:G:C	F189L	0.992
1:156245184:G:T	F189L	0.992
1:156245186:A:G	F189L	0.992
1:156245811:T:A	D119V	0.992
1:156244395:G:C	H257D	0.991
1:156245786:A:C	S127R	0.990
1:156245786:A:T	S127R	0.990
1:156245788:T:G	S127R	0.990
1:156245810:G:C	D119E	0.989
1:156245810:G:T	D119E	0.989
1:156244365:C:G	G267R	0.988
1:156244403:C:T	G254D	0.988
1:156245811:T:G	D119A	0.987
1:156245861:G:C	H102Q	0.987

dbSNP variants (sampled 300 via entrez): RS1001247691 (1:156247687 A>C), RS1001867145 (1:156247908 G>A), RS1002070456 (1:156242923 G>A), RS1002653956 (1:156246626 C>A), RS1003836043 (1:156243788 ACCAGAAACGGAG>A), RS1003864063 (1:156245419 G>A), RS1004119202 (1:156243908 T>A,C), RS1004261591 (1:156249077 T>C), RS1004560416 (1:156244729 C>T), RS1005145681 (1:156248396 AAC>A), RS1005221366 (1:156247381 C>A), RS1005260117 (1:156248166 C>T), RS1005624751 (1:156247183 G>A), RS1006565473 (1:156248015 G>A), RS1007203936 (1:156245996 G>A,C)

Disease associations

OMIM: gene MIM:614579 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000582_7	Mean corpuscular hemoglobin concentration	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004528	mean corpuscular hemoglobin concentration

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
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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