GPR83

Summary

GPR83 (G protein-coupled receptor 83, HGNC:4523) is a protein-coding gene on chromosome 11q21, encoding G-protein coupled receptor 83 (Q9NYM4). G-protein coupled receptor for PEN, a neuropeptide produced from the precursor protein, proSAAS (encoded by PCSK1N).

Predicted to enable neuropeptide receptor activity. Predicted to be involved in neuropeptide signaling pathway and phospholipase C-activating G protein-coupled receptor signaling pathway. Predicted to act upstream of or within response to glucocorticoid. Located in cilium.

Source: NCBI Gene 10888 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 87 total
• Druggable target: yes
• MANE Select transcript: NM_016540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4523
Approved symbol	GPR83
Name	G protein-coupled receptor 83
Location	11q21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123901
Ensembl biotype	protein_coding
OMIM	605569
Entrez	10888

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000243673, ENST00000539203

RefSeq mRNA: 2 — MANE Select: NM_016540 NM_001330345, NM_016540

CCDS: CCDS81616, CCDS8297

Canonical transcript exons

ENST00000243673 — 4 exons

Exon	Start	End
ENSE00000842832	94377316	94380773
ENSE00000915746	94396399	94396524
ENSE00000915747	94393485	94393618
ENSE00000989384	94400861	94401419

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 86.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5472 / max 87.3981, expressed in 152 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121843	0.4425	143
121844	0.0496	25
121841	0.0349	23
121842	0.0202	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	86.76	gold quality
cerebellum	UBERON:0002037	80.74	gold quality
middle temporal gyrus	UBERON:0002771	80.33	gold quality
cerebellar cortex	UBERON:0002129	80.32	gold quality
cerebellar hemisphere	UBERON:0002245	80.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.17	gold quality
Brodmann (1909) area 23	UBERON:0013554	72.96	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.79	gold quality
superior frontal gyrus	UBERON:0002661	71.70	gold quality
pancreatic ductal cell	CL:0002079	70.91	silver quality
dorsal root ganglion	UBERON:0000044	69.96	gold quality
prefrontal cortex	UBERON:0000451	69.46	gold quality
entorhinal cortex	UBERON:0002728	69.30	gold quality
postcentral gyrus	UBERON:0002581	69.29	gold quality
secondary oocyte	CL:0000655	69.11	silver quality
frontal cortex	UBERON:0001870	69.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	68.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.60	gold quality
right frontal lobe	UBERON:0002810	68.10	gold quality
neocortex	UBERON:0001950	68.04	gold quality
Ammon’s horn	UBERON:0001954	67.88	gold quality
anterior cingulate cortex	UBERON:0009835	67.87	gold quality
cerebral cortex	UBERON:0000956	67.76	gold quality
hypothalamus	UBERON:0001898	67.60	gold quality
Brodmann (1909) area 46	UBERON:0006483	67.57	silver quality
primary visual cortex	UBERON:0002436	67.50	gold quality
parietal lobe	UBERON:0001872	67.06	gold quality
caudate nucleus	UBERON:0001873	64.72	gold quality
brain	UBERON:0000955	64.55	gold quality
putamen	UBERON:0001874	63.81	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.25
E-MTAB-9543	no	1.22
E-MTAB-4850	no	0.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting GPR83, 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-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 3)

• GPR83 is 2- to 7-fold up-regulated in all indvidual human CD4+CD25+ T regulatory cell populations analyzed and is directly linked to Foxp3 expression. (PMID:16785516)
• results suggest that the 20 additional aminoacids within GPR83 isoform-4 are involved in Treg induction during inflammatory immune responses (PMID:20200545)
• A Pilot Screen of a Novel Peptide Hormone Library Identified Candidate GPR83 Ligands. (PMID:32713278)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr83	ENSDARG00000058120
mus_musculus	Gpr83	ENSMUSG00000031932
rattus_norvegicus	Gpr83	ENSRNOG00000030318
caenorhabditis_elegans		WBGENE00006428

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MTNR1B (ENSG00000134640), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), NPY5R (ENSG00000164129), MTNR1A (ENSG00000168412), PROKR1 (ENSG00000169618), TACR3 (ENSG00000169836), OR9G1 (ENSG00000174914), OR11H4 (ENSG00000176198), OR11H6 (ENSG00000176219), OR9A2 (ENSG00000179468), GPR88 (ENSG00000181656), GPR19 (ENSG00000183150), NPY2R (ENSG00000185149), OR11G2 (ENSG00000196832), NPY4R (ENSG00000204174), OR11A1 (ENSG00000204694), OR9A1P (ENSG00000237621), OR11H12 (ENSG00000257115), OR9A4 (ENSG00000258083), OR11H2 (ENSG00000258453), OR11H7 (ENSG00000258806), NPY4R2 (ENSG00000264717), OR10X1 (ENSG00000279111), OR51F1 (ENSG00000280021)

Protein

Protein identifiers

G-protein coupled receptor 83 — Q9NYM4 (reviewed: Q9NYM4)

Alternative names: G-protein coupled receptor 72

All UniProt accessions (1): Q9NYM4

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for PEN, a neuropeptide produced from the precursor protein, proSAAS (encoded by PCSK1N). Acts through a G(i)- and G(q)-alpha-mediated pathway in response to PEN. Plays a role in food intake and body weight regulation. May contribute to the regulation of anxiety-related behaviors.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in the brain and spinal cord, and found in lower concentrations in the thymus and other tissues.

Miscellaneous. NPY has been reported to be a ligand for GPR83 (in vitro). However, a more recent study found that radiolabeled PEN binding to GPR83 is not affected by NPY concentrations below 1 mM, only very high, non-physiological concentrations causes a partial, displacement of PEN binding.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NYM4-1	1	yes
Q9NYM4-2	2

RefSeq proteins (2): NP_001317274, NP_057624* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000611	NPY_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (26 total): topological domain 8, transmembrane region 7, glycosylation site 3, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYM4-F1	76.29	0.42

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): 144–224

Glycosylation sites (3): 37, 46, 134

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 141 (showing top): GOBP_BEHAVIOR, GOBP_RESPONSE_TO_CORTICOSTEROID, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CTAGGAA_MIR384, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_PHOSPHOLIPASE_C_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GAVIN_FOXP3_TARGETS_CLUSTER_T7, GAVIN_FOXP3_TARGETS_CLUSTER_P4, GAVIN_IL2_RESPONSIVE_FOXP3_TARGETS_UP, GOBP_FEEDING_BEHAVIOR, GOCC_CILIUM

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), neuropeptide signaling pathway (GO:0007218), feeding behavior (GO:0007631), response to glucocorticoid (GO:0051384), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), neuropeptide Y receptor activity (GO:0004983), neuropeptide receptor activity (GO:0008188)

GO Cellular Component (4): plasma membrane (GO:0005886), cilium (GO:0005929), non-motile cilium (GO:0097730), 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	3
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
behavior	1
response to corticosteroid	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
neuropeptide receptor activity	1
neuropeptide signaling pathway	1
G protein-coupled peptide receptor activity	1
neuropeptide binding	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
cellular anatomical structure	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR83	GPR171	O14626	727
GPR83	NPY	P01303	717
GPR83	ADCY3	O60266	714
GPR83	PROK1	P58294	698
GPR83	PCSK1N	Q9UHG2	694
GPR83	PROK2	Q9HC23	657
GPR83	ALDH18A1	P54886	609
GPR83	FOXP3	Q9BZS1	595
GPR83	ADCY8	P40145	552
GPR83	QRFP	P83859	534
GPR83	RARRES2	Q99969	515
GPR83	GPR157	Q5UAW9	498
GPR83	GPR150	Q8NGU9	485
GPR83	CMKLR2	P46091	466
GPR83	GPR139	Q6DWJ6	453

IntAct

2 interactions, top by confidence:

A	B	Type	Score
GPR83	ACVR1B	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): DDR1 (Affinity Capture-MS), ACVR1B (Affinity Capture-MS)

ESM2 similar proteins: A5A4K9, A5A4L1, B2ZI34, O08725, O08786, O42329, O43193, O54799, O97772, P11616, P21729, P24053, P25099, P26684, P28088, P28190, P28336, P28646, P30542, P30550, P30551, P30731, P30872, P30873, P32238, P33534, P34970, P34975, P35342, P41145, P47745, P47751, P52500, P60893, P60894, P60895, Q2KIP6, Q49LX5, Q5D0K2, Q5RBG7

Diamond homologs: G4WMX4, O02813, O02835, O02836, O18935, O19012, O19032, O19091, O42179, O43614, O62809, O77408, O77700, O77713, O77721, O97512, P05363, P08909, P14416, P14600, P16177, P16610, P18089, P18825, P19328, P20288, P21452, P22086, P24628, P25103, P25931, P29371, P30098, P30545, P30547, P30549, P30731, P30938, P30974, P30975

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

325 predictions. Top by Δscore:

Variant	Effect	Δscore
11:94380787:G:C	acceptor_gain	1.0000
11:94380787:G:GC	acceptor_gain	1.0000
11:94393479:TCTCA:T	donor_loss	1.0000
11:94393480:CTCAC:C	donor_loss	1.0000
11:94393481:TCACC:T	donor_loss	1.0000
11:94393482:CA:C	donor_loss	1.0000
11:94393615:TGAC:T	acceptor_gain	1.0000
11:94393618:CCTGG:C	acceptor_loss	1.0000
11:94393619:C:A	acceptor_loss	1.0000
11:94393619:C:CC	acceptor_gain	1.0000
11:94393620:T:G	acceptor_loss	1.0000
11:94400857:TTACC:T	donor_loss	1.0000
11:94400858:TACC:T	donor_loss	1.0000
11:94380769:CCTCA:C	acceptor_gain	0.9900
11:94380770:CTCAC:C	acceptor_gain	0.9900
11:94380771:TCA:T	acceptor_gain	0.9900
11:94380771:TCACT:T	acceptor_gain	0.9900
11:94380772:CA:C	acceptor_gain	0.9900
11:94380772:CAC:C	acceptor_gain	0.9900
11:94380774:C:CA	acceptor_loss	0.9900
11:94380774:C:CC	acceptor_gain	0.9900
11:94380781:C:CT	acceptor_gain	0.9900
11:94380782:A:T	acceptor_gain	0.9900
11:94393541:AG:A	donor_gain	0.9900
11:94393542:G:C	donor_gain	0.9900
11:94393616:GAC:G	acceptor_gain	0.9900
11:94400855:CCTTA:C	donor_loss	0.9900
11:94400856:CTTAC:C	donor_loss	0.9900
11:94400859:A:AC	donor_gain	0.9900
11:94400860:C:CC	donor_gain	0.9900

AlphaMissense

2784 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:94380413:G:C	S336R	0.999
11:94380413:G:T	S336R	0.999
11:94380415:T:G	S336R	0.999
11:94380518:A:C	F301L	0.998
11:94380518:A:T	F301L	0.998
11:94380520:A:G	F301L	0.998
11:94380750:C:G	C224S	0.998
11:94380751:A:T	C224S	0.998
11:94393552:A:G	W194R	0.998
11:94393552:A:T	W194R	0.998
11:94396471:G:C	S147R	0.998
11:94396471:G:T	S147R	0.998
11:94396473:T:G	S147R	0.998
11:94396481:C:G	C144S	0.998
11:94396482:A:T	C144S	0.998
11:94396501:C:A	W137C	0.998
11:94396501:C:G	W137C	0.998
11:94396503:A:G	W137R	0.998
11:94396503:A:T	W137R	0.998
11:94400912:G:C	N112K	0.998
11:94400912:G:T	N112K	0.998
11:94380410:G:C	S337R	0.997
11:94380410:G:T	S337R	0.997
11:94380412:T:G	S337R	0.997
11:94380420:G:T	A334D	0.997
11:94380751:A:G	C224R	0.997
11:94396480:G:C	C144W	0.997
11:94396481:C:T	C144Y	0.997
11:94396482:A:G	C144R	0.997
11:94380427:A:G	W332R	0.996

dbSNP variants (sampled 300 via entrez): RS1000255824 (11:94397030 T>C), RS1000340762 (11:94387082 G>A,T), RS1000369209 (11:94385433 G>T), RS1000371783 (11:94387234 T>C), RS1000384596 (11:94392612 A>C,G), RS1000482109 (11:94391244 ATGT>A), RS1000523371 (11:94403104 C>A,T), RS1000545316 (11:94381735 C>T), RS1000924589 (11:94383178 A>C), RS1001022015 (11:94385629 G>A), RS1001120211 (11:94402424 A>G), RS1001129723 (11:94401856 G>A,C,T), RS1001477676 (11:94402099 A>T), RS1001509135 (11:94401597 C>T), RS1001514379 (11:94393131 A>C)

Disease associations

OMIM: gene MIM:605569 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001518_5	Response to angiotensin II receptor blocker therapy (opposite direction w/ diuretic therapy)	2.000000e-06
GCST003674_2	Obstructive sleep apnea trait (apnea hypopnea index)	2.000000e-08
GCST009391_1885	Metabolite levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007817	sleep apnea measurement
EFO:0010414	triacylglycerol 52:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523924 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3758785	Efficacy	3	hydrochlorothiazide	Essential hypertension
rs3758785	Efficacy	3	candesartan	Essential hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3758785	GPR83	3	0.00	2	hydrochlorothiazide;candesartan

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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
PEN	Agonist	10.74	pEC50
PEN	Agonist	8.1	pKd
Zn2+	Full agonist	5.0	pEC50

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression, decreases expression	4
Resveratrol	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
quercitrin	increases expression	1
terbufos	increases methylation	1
perfluorooctanoic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	affects expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Cytarabine	decreases expression	1
Fonofos	increases methylation	1
Hydralazine	affects cotreatment, increases expression	1
Parathion	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Medroxyprogesterone Acetate	decreases 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
CHEMBL4883470	Binding	PRESTO-Tango GPCRome screening (GPR83)	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_KX74	PathHunter CHO-K1 GPR83 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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