GPR63

Summary

GPR63 (G protein-coupled receptor 63, HGNC:13302) is a protein-coding gene on chromosome 6q16.1, encoding Probable G-protein coupled receptor 63 (Q9BZJ6). Orphan receptor.

Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cytosol; nucleoplasm; and plasma membrane. Part of receptor complex.

Source: NCBI Gene 81491 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• Druggable target: yes
• MANE Select transcript: NM_030784

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13302
Approved symbol	GPR63
Name	G protein-coupled receptor 63
Location	6q16.1
Locus type	gene with protein product
Status	Approved
Aliases	PSP24(beta), PSP24B
Ensembl gene	ENSG00000112218
Ensembl biotype	protein_coding
OMIM	606915
Entrez	81491

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000229955, ENST00000857872, ENST00000857873, ENST00000857874, ENST00000857875, ENST00000857876, ENST00000917063, ENST00000917064

RefSeq mRNA: 2 — MANE Select: NM_030784 NM_001143957, NM_030784

CCDS: CCDS5036

Canonical transcript exons

ENST00000229955 — 2 exons

Exon	Start	End
ENSE00003547771	96794125	96799881
ENSE00003695172	96837268	96837477

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 81.49.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9666 / max 57.8082, expressed in 698 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74772	1.5375	627
74773	0.2213	117
74774	0.2079	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.99	gold quality
cortical plate	UBERON:0005343	76.21	gold quality
ventricular zone	UBERON:0003053	72.32	gold quality
ganglionic eminence	UBERON:0004023	70.83	gold quality
popliteal artery	UBERON:0002250	70.65	gold quality
tibial artery	UBERON:0007610	70.61	gold quality
prefrontal cortex	UBERON:0000451	67.38	gold quality
right coronary artery	UBERON:0001625	66.79	gold quality
rectum	UBERON:0001052	66.76	gold quality
aorta	UBERON:0000947	66.38	gold quality
embryo	UBERON:0000922	65.10	gold quality
left coronary artery	UBERON:0001626	64.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.06	gold quality
body of pancreas	UBERON:0001150	63.70	gold quality
buccal mucosa cell	CL:0002336	63.58	silver quality
coronary artery	UBERON:0001621	63.40	gold quality
secondary oocyte	CL:0000655	63.31	silver quality
colonic epithelium	UBERON:0000397	63.17	silver quality
islet of Langerhans	UBERON:0000006	63.15	gold quality
mucosa of transverse colon	UBERON:0004991	62.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.73	gold quality
pancreas	UBERON:0001264	62.66	gold quality
descending thoracic aorta	UBERON:0002345	62.63	gold quality
right adrenal gland cortex	UBERON:0035827	62.37	gold quality
right adrenal gland	UBERON:0001233	62.25	gold quality
anterior cingulate cortex	UBERON:0009835	61.98	gold quality
cingulate cortex	UBERON:0003027	61.94	gold quality
frontal cortex	UBERON:0001870	61.86	gold quality
neocortex	UBERON:0001950	61.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

243 targeting GPR63, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 1)

• Endothelial cell-derived S1P promotes migration and stemness by binding with GPR63 in colorectal cancer. (PMID:36371997)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr63	ENSDARG00000074540
mus_musculus	Gpr63	ENSMUSG00000040372
rattus_norvegicus	Gpr63	ENSRNOG00000007675

Paralogs (3): GPR45 (ENSG00000135973), GPR26 (ENSG00000154478), GPR78 (ENSG00000155269)

Protein

Protein identifiers

Probable G-protein coupled receptor 63 — Q9BZJ6 (reviewed: Q9BZJ6)

Alternative names: PSP24-2, PSP24-beta

All UniProt accessions (2): Q9BZJ6, A8K1C4

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor. May play a role in brain function.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in brain; detected in the frontal cortex, with lower levels in the thalamus, caudate, hypothalamus and midbrain.

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

RefSeq proteins (2): NP_001137429, NP_110411* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR051880	GPC_Orphan_Receptors	Family

Pfam: PF00001

UniProt features (20 total): topological domain 8, transmembrane region 7, glycosylation site 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZJ6-F1	75.52	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.

Glycosylation sites (3): 16, 28, 62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, FOXO1_01, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, ZHAN_MULTIPLE_MYELOMA_CD1_UP, TGCTGAY_UNKNOWN, AACTTT_UNKNOWN, ZHAN_MULTIPLE_MYELOMA_CD1_VS_CD2_UP, LEIN_CEREBELLUM_MARKERS, GOCC_RECEPTOR_COMPLEX, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, ROVERSI_GLIOMA_COPY_NUMBER_DN, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, CCTNTMAGA_UNKNOWN

GO Biological Process (2): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

GO Molecular Function (1): G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
protein-containing complex	1

Protein interactions and networks

STRING

654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR63	KLHL32	Q96NJ5	668
GPR63	GPR88	Q9GZN0	589
GPR63	COXFA4	O00483	519
GPR63	GPR150	Q8NGU9	501
GPR63	GPR52	Q9Y2T5	491
GPR63	GPR22	Q99680	483
GPR63	ZNF222	Q9UK12	474
GPR63	GPR27	Q9NS67	470
GPR63	MMS22L	Q6ZRQ5	462
GPR63	GPR87	Q9BY21	455
GPR63	GPR61	Q9BZJ8	454
GPR63	GPR3	P46089	453
GPR63	NDUFAF4	Q9P032	451
GPR63	GPR6	P46095	438
GPR63	GPRC5C	Q9NQ84	429

IntAct

5 interactions, top by confidence:

A	B	Type	Score
GPR63	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
FYN	GPR63	psi-mi:“MI:0915”(physical association)	0.400
GPR63	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR63	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): GPR63 (Protein-peptide)

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B3DM66, B4XF06, D4A3U0, O02777, O43194, O46635, P08909, P08911, P0C0W8, P14842, P18599, P20272, P21554, P28223, P28335, P32240, P34311, P34968, P35363, P47746, P50128, P50129, P56971, P70259, Q09502, Q333S9, Q5IS53, Q5IS66, Q5IS73, Q5IS98, Q5R4Q6, Q5U431, Q60F97, Q6DWJ6, Q71SP5, Q75Z89, Q801M1, Q80UC8

Diamond homologs: A0A2L0VBG2, O18821, O42329, O77808, O88721, P30518, P30560, P30968, P30969, P32236, P32237, P32307, P37288, P48044, P49922, P70536, P97266, Q00788, Q01776, Q18775, Q19PY9, Q24563, Q25188, Q2V2K5, Q5QD12, Q5QD21, Q63384, Q8CH60, Q8IS44, Q8SPZ1, Q90252, Q90334, Q923X8, Q923Y2, Q93126, Q95JG1, Q95MG6, Q95MH6, Q96P88, Q9BZJ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

659 predictions. Top by Δscore:

Variant	Effect	Δscore
6:96799883:T:A	acceptor_loss	1.0000
6:96837345:T:A	donor_gain	1.0000
6:96799877:TTTGC:T	acceptor_gain	0.9900
6:96799878:TTGC:T	acceptor_gain	0.9900
6:96799879:TGC:T	acceptor_gain	0.9900
6:96799880:GC:G	acceptor_gain	0.9900
6:96799881:CC:C	acceptor_gain	0.9900
6:96799882:C:CC	acceptor_gain	0.9900
6:96799888:A:AC	acceptor_gain	0.9900
6:96837263:CTCA:C	donor_loss	0.9900
6:96837264:TCAC:T	donor_loss	0.9900
6:96837266:ACC:A	donor_loss	0.9900
6:96837267:C:CG	donor_loss	0.9900
6:96799888:A:C	acceptor_gain	0.9800
6:96799895:C:CT	acceptor_gain	0.9800
6:96801931:ACCCT:A	acceptor_gain	0.9800
6:96837360:T:TA	donor_gain	0.9800
6:96801932:CCCT:C	acceptor_gain	0.9600
6:96799882:C:T	acceptor_gain	0.9500
6:96799896:A:T	acceptor_gain	0.9500
6:96837268:C:G	donor_loss	0.9400
6:96837364:T:A	donor_gain	0.9400
6:96829409:TAGG:T	donor_gain	0.9300
6:96829410:AGGA:A	donor_gain	0.9300
6:96799895:C:T	acceptor_gain	0.9200
6:96798442:A:AC	donor_gain	0.9100
6:96829411:G:C	donor_gain	0.9100
6:96837262:CCTCA:C	donor_gain	0.9100
6:96799878:TTGCC:T	acceptor_gain	0.9000
6:96799879:TGCCT:T	acceptor_gain	0.9000

AlphaMissense

2778 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:96799196:C:A	R179M	0.999
6:96799204:G:C	S176R	0.999
6:96799204:G:T	S176R	0.999
6:96799206:T:G	S176R	0.999
6:96799291:C:A	W147C	0.999
6:96799291:C:G	W147C	0.999
6:96799366:G:C	S122R	0.999
6:96799366:G:T	S122R	0.999
6:96799368:T:G	S122R	0.999
6:96798598:G:C	F378L	0.998
6:96798598:G:T	F378L	0.998
6:96798600:A:G	F378L	0.998
6:96798805:T:A	K309N	0.998
6:96798805:T:G	K309N	0.998
6:96799046:C:G	C229S	0.998
6:96799047:A:G	C229R	0.998
6:96799047:A:T	C229S	0.998
6:96799125:A:G	W203R	0.998
6:96799125:A:T	W203R	0.998
6:96799271:C:G	C154S	0.998
6:96799271:C:T	C154Y	0.998
6:96799272:A:T	C154S	0.998
6:96799293:A:G	W147R	0.998
6:96799293:A:T	W147R	0.998
6:96799373:A:T	L120H	0.998
6:96799381:G:C	N117K	0.998
6:96799381:G:T	N117K	0.998
6:96798599:A:G	F378S	0.997
6:96798629:G:T	P368Q	0.997
6:96799195:C:A	R179S	0.997

dbSNP variants (sampled 300 via entrez): RS1000129843 (6:96794533 T>C), RS1000173413 (6:96801731 T>G), RS1000213945 (6:96821859 T>C), RS1000225906 (6:96802006 T>C), RS1000435712 (6:96821098 G>A,C), RS1000493276 (6:96828514 T>C,G), RS1000507849 (6:96803379 T>C), RS1000569770 (6:96803774 T>C,G), RS1000733417 (6:96807199 C>G), RS1000738784 (6:96828227 T>C), RS1000797980 (6:96810910 A>G), RS1000862238 (6:96809447 T>C), RS1000914741 (6:96799544 C>A), RS1001068133 (6:96796265 C>A), RS1001097000 (6:96839100 A>G,T)

Disease associations

OMIM: gene MIM:606915 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005342_1	Plasma kynurenine levels in major depressive disorder	7.000000e-06
GCST010989_107	Body size at age 10	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008529	kynurenine measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523916 (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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
dioleoylphosphatidic acid	Full agonist	6.3	pEC50
sphingosine 1-phosphate	Full agonist	6.18	pEC50
dihydrosphingosine 1-phosphate	Full agonist	6.17	pEC50

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
quercitrin	increases expression	1
arsenite	decreases methylation	1
sodium arsenite	affects methylation	1
potassium chromate(VI)	increases expression	1
ferrous chloride	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Naphthoquinones	increases expression	1
Valproic Acid	decreases expression	1
Vincristine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1
Particulate Matter	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
CHEMBL4883462	Binding	PRESTO-Tango GPCRome screening (GPR63)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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