GPR32

Summary

GPR32 (G protein-coupled receptor 32, HGNC:4487) is a protein-coding gene on chromosome 19q13.33, encoding Probable G-protein coupled receptor 32 (O75388). G-protein coupled receptor that binds to several ligands including resolvin D1 (RvD1) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways.

This gene is intronless and encodes a member of the G-protein coupled receptor 1 family. The encoded protein binds to resolvin D1 and lipoxin A4 and has been linked to pulmonary inflammation. A related pseudogene has been identified on chromosome 19.

Source: NCBI Gene 2854 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• MANE Select transcript: NM_001506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4487
Approved symbol	GPR32
Name	G protein-coupled receptor 32
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	RVDR1, DRV1
Ensembl gene	ENSG00000142511
Ensembl biotype	protein_coding
OMIM	603195
Entrez	2854

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000270590

RefSeq mRNA: 1 — MANE Select: NM_001506 NM_001506

CCDS: CCDS12801

Canonical transcript exons

ENST00000270590 — 1 exons

Exon	Start	End
ENSE00000954608	50770464	50771732

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 79.96.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	79.96	gold quality
buccal mucosa cell	CL:0002336	72.20	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	68.77	gold quality
vena cava	UBERON:0004087	68.09	gold quality
cerebellar vermis	UBERON:0004720	64.17	gold quality
pharyngeal mucosa	UBERON:0000355	63.72	gold quality
body of tongue	UBERON:0011876	63.32	gold quality
saphenous vein	UBERON:0007318	62.57	gold quality
pericardium	UBERON:0002407	62.38	gold quality
inferior vagus X ganglion	UBERON:0005363	62.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	62.14	gold quality
nipple	UBERON:0002030	62.05	gold quality
subthalamic nucleus	UBERON:0001906	62.00	gold quality
tongue	UBERON:0001723	61.96	gold quality
cardia of stomach	UBERON:0001162	61.93	gold quality
pons	UBERON:0000988	61.81	gold quality
superior surface of tongue	UBERON:0007371	61.81	gold quality
medulla oblongata	UBERON:0001896	61.79	gold quality
pylorus	UBERON:0001166	61.76	gold quality
trigeminal ganglion	UBERON:0001675	61.76	gold quality
substantia nigra pars compacta	UBERON:0001965	61.75	gold quality
synovial joint	UBERON:0002217	61.74	gold quality
dorsal root ganglion	UBERON:0000044	61.68	gold quality
ventral tegmental area	UBERON:0002691	61.68	gold quality
superior vestibular nucleus	UBERON:0007227	61.59	gold quality
lateral globus pallidus	UBERON:0002476	61.58	gold quality
lateral nuclear group of thalamus	UBERON:0002736	61.46	gold quality
dorsal plus ventral thalamus	UBERON:0001897	61.23	gold quality
penis	UBERON:0000989	61.17	gold quality
renal medulla	UBERON:0000362	60.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.32

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

• results indicate that RvD1 specifically interacts with both ALX and GPR32 on phagocytes. (PMID:20080636)
• Results suggest that resolvin D1 inhibited TGF-beta1-induced EMT via ALX/FPR2 and GPR32 by reducing the expression of ZEB1. (PMID:24120851)
• The effects of diclofenac on the incidence of pancreatitis following endoscopic retrograde cholangiopancreatography via lipoxin A4 and resolvin D1 and E1 levels is reported. (PMID:25030943)
• Resolvin D1 attenuates the viral mimic-induced inflammatory signaling in human airway epithelial cells via TAK1. (PMID:25320283)
• Our findings indicate that chitotriosidase and S10012A are useful in diagnosis and detection of subclinical inflammation and/or assessment of disease activity in FMF patients. (PMID:26339162)
• Data suggest that resolvin D1/RVDR1 signaling (1) promotes epithelial wound repair, (2) inhibits TGFB-induced epithelial-mesenchymal transition in type II alveolar cells, (3) inhibits fibroproliferation and apoptosis, (4) reduces effects of TGFB on primary lung fibroblast collagen production, and (5) inhibits myofibroblast differentiation. (TGFB = transforming growth factor beta) (PMID:29083412)
• SPM Receptor Expression and Localization in Irradiated Salivary Glands. (PMID:34339312)
• The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection. (PMID:34699386)

Cross-species orthologs

0 orthologs

Paralogs (8): C5AR2 (ENSG00000134830), FPR2 (ENSG00000171049), FPR1 (ENSG00000171051), C3AR1 (ENSG00000171860), CMKLR1 (ENSG00000174600), FPR3 (ENSG00000187474), C5AR1 (ENSG00000197405), GPR33 (ENSG00000214943)

Protein

Protein identifiers

Probable G-protein coupled receptor 32 — O75388 (reviewed: O75388)

All UniProt accessions (2): O75388, H9NIL6

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor that binds to several ligands including resolvin D1 (RvD1) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. In macrophages, enhances the RvD1-stimulated phagocytic and clearance functions. Macrophages migrate less toward different chemoattractant stimuli but phagocytose more microbial particles. Prevents the increase in Ca(2+) and activation of ERK1/2 used by histamine and its H1 receptor subtype to induce goblet cell secretion by activating PKC and GRK2 to counter-regulate the histamine receptor.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in resting primary human macrophages.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_001497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000826	Formyl_rcpt-rel	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (22 total): topological domain 8, transmembrane region 7, glycosylation site 2, sequence conflict 2, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75388-F1	81.01	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 114–191

Glycosylation sites (2): 30, 199

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 36 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_PHOSPHOLIPASE_C_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, GOBP_COMPLEMENT_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOMF_COMPLEMENT_RECEPTOR_ACTIVITY, GOMF_N_FORMYL_PEPTIDE_RECEPTOR_ACTIVITY, NOTCH_DN.V1_DN, NFE2L2.V2, GOMF_IMMUNE_RECEPTOR_ACTIVITY

GO Biological Process (6): complement receptor mediated signaling pathway (GO:0002430), inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), signal transduction (GO:0007165)

GO Molecular Function (3): complement receptor activity (GO:0004875), G protein-coupled receptor activity (GO:0004930), N-formyl peptide receptor activity (GO:0004982)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
transmembrane signaling receptor activity	2
immune response-activating cell surface receptor signaling pathway	1
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
regulation of biological quality	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
complement binding	1
complement receptor mediated signaling pathway	1
immune receptor activity	1
G protein-coupled peptide receptor activity	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
GPR32	HSH2D	Q96JZ2	822
GPR32	ALOX15	P16050	720
GPR32	GFER	P55789	675
GPR32	ANXA1	P04083	656
GPR32	GPR37	O15354	603
GPR32	ARRB2	P32121	591
GPR32	LGR6	Q9HBX8	548
GPR32	LTB4R	Q15722	531
GPR32	ALOX5	P09917	507
GPR32	FFAR1	O14842	484
GPR32	RARRES2	Q99969	483
GPR32	CMKLR1	Q99788	473
GPR32	TAS2R9	Q9NYW1	460
GPR32	FPR2	P25090	449
GPR32	GPR101	Q96P66	435

IntAct

8 interactions, top by confidence:

A	B	Type	Score
GPR32	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR32	psi-mi:“MI:0915”(physical association)	0.400
GPR32	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
GPR32	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR32	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	GPR32	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A4FUQ5, B9VR26, O08790, O35786, O70129, O75388, O88416, O88536, O88537, O97664, P0C7U4, P21462, P21730, P25089, P25090, P30992, P30993, P33766, P35343, P35407, P46090, P46091, P79175, P79176, P79177, P79178, P79188, P79189, P79190, P79191, P79234, P79235, P79236, P79237, P79240, P79241, P79242, P79243, P97468, P97520

Diamond homologs: A0A2L0VBG2, E7EM37, E9QJ73, O18821, O18935, O19012, O19014, O19025, O19032, O42329, O62169, O75388, O77700, O77713, O77715, O77721, O77830, O88634, P16395, P30968, P30969, P32236, P32237, P32251, P49651, P49922, P97288, Q01776, Q15722, Q19PY9, Q29003, Q2V2K5, Q6UNA4, Q6XKD3, Q8CH60, Q8JG69, Q8JG70, Q8MJ88, Q8NGA4, Q8SPZ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

189 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50770565:A:AG	donor_gain	0.8500
19:50770501:ATT:A	donor_gain	0.7500
19:50770527:TGACA:T	donor_gain	0.7300
19:50770528:GACAG:G	donor_gain	0.7300
19:50770529:ACAGA:A	donor_gain	0.7300
19:50771417:AACGT:A	acceptor_gain	0.7200
19:50771405:T:TA	acceptor_gain	0.6800
19:50770565:A:G	donor_gain	0.6500
19:50771419:C:G	acceptor_gain	0.6200
19:50771417:A:AG	acceptor_gain	0.6100
19:50771419:C:CA	acceptor_gain	0.6100
19:50771421:T:TA	acceptor_gain	0.5800
19:50771557:T:TA	acceptor_gain	0.5700
19:50771418:ACGT:A	acceptor_gain	0.5600
19:50771441:T:TA	acceptor_gain	0.5500
19:50771417:AAC:A	acceptor_gain	0.5200
19:50771412:C:CA	acceptor_gain	0.5000
19:50771499:C:T	donor_gain	0.4900
19:50771548:C:G	acceptor_gain	0.4900
19:50770502:T:G	donor_gain	0.4800
19:50771448:G:A	acceptor_gain	0.4800
19:50771010:T:TA	acceptor_gain	0.4700
19:50771463:A:T	donor_gain	0.4700
19:50771418:A:G	acceptor_gain	0.4600
19:50771379:TGCTG:T	donor_loss	0.4500
19:50771381:CTGGT:C	donor_loss	0.4500
19:50771382:TGGT:T	donor_loss	0.4500
19:50771383:GG:G	donor_loss	0.4500
19:50771384:G:GC	donor_loss	0.4500
19:50771385:T:G	donor_loss	0.4500

AlphaMissense

2304 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50771273:T:C	F225L	0.974
19:50771275:C:A	F225L	0.974
19:50771275:C:G	F225L	0.974
19:50770921:G:C	W107C	0.971
19:50770921:G:T	W107C	0.971
19:50771501:A:C	S301R	0.970
19:50771503:C:A	S301R	0.970
19:50771503:C:G	S301R	0.970
19:50771393:T:C	F265L	0.968
19:50771395:C:A	F265L	0.968
19:50771395:C:G	F265L	0.968
19:50770919:T:A	W107R	0.960
19:50770919:T:C	W107R	0.960
19:50771096:T:A	W166R	0.959
19:50771096:T:C	W166R	0.959
19:50771528:A:C	S310R	0.954
19:50771530:C:A	S310R	0.954
19:50771530:C:G	S310R	0.954
19:50771525:A:C	S309R	0.942
19:50771527:C:A	S309R	0.942
19:50771527:C:G	S309R	0.942
19:50771504:T:C	F302L	0.941
19:50771506:T:A	F302L	0.941
19:50771506:T:G	F302L	0.941
19:50771171:T:A	C191S	0.939
19:50771172:G:C	C191S	0.939
19:50770982:A:C	S128R	0.935
19:50770984:T:A	S128R	0.935
19:50770984:T:G	S128R	0.935
19:50771135:T:C	F179L	0.932

dbSNP variants (sampled 300 via entrez): RS1001239877 (19:50772028 T>C), RS1001269522 (19:50768606 T>C), RS1001272378 (19:50771658 C>G,T), RS1002290958 (19:50770168 G>T), RS1003018761 (19:50768889 A>C), RS1003265650 (19:50771100 T>G), RS1004544664 (19:50769402 T>C), RS1004577314 (19:50769221 T>G), RS1005579709 (19:50770621 G>T), RS1005719079 (19:50769526 A>G), RS1006753971 (19:50771052 A>T), RS1007134018 (19:50770812 G>A), RS1007706663 (19:50772230 G>A,C,T), RS1009615752 (19:50768881 G>A), RS1010572315 (19:50770471 C>T)

Disease associations

OMIM: gene MIM:603195 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010536_5	Carotid plaque maximum area	5.000000e-06
GCST010538_6	Sum of carotid plaque area	2.000000e-07
GCST010539_7	Sum of stenosis	3.000000e-06
GCST011039_8	Parkinson’s disease progression (composite)	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006501	carotid plaque build
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523863 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Class A Orphans with emerging pharmacology

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
RvD1-ME	Full agonist	11.34	pEC50
resolvin D1	Full agonist	11.06	pEC50
[3H]resolvin D1	Agonist	9.7	pKd
LXA4	Full agonist	9.7	pEC50

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, affects cotreatment, decreases expression	2
kojic acid	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arbutin	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Carmustine	decreases expression	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dust	increases secretion	1
Indomethacin	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883446	Binding	PRESTO-Tango GPCRome screening (GPR32)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX58	PathHunter CHO-K1 GPR32 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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