GPR87

Summary

GPR87 (G protein-coupled receptor 87, HGNC:4538) is a protein-coding gene on chromosome 3q25.1, encoding G-protein coupled receptor 87 (Q9BY21). Receptor for lysophosphatidic acid (LPA).

This gene encodes a G protein-coupled receptor and is located in a cluster of G protein-couple receptor genes on chromosome 3. The encoded protein has been shown to be overexpressed in lung squamous cell carcinoma (PMID:18057535) and regulated by p53 (PMID:19602589).

Source: NCBI Gene 53836 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 59 total
• Druggable target: yes
• MANE Select transcript: NM_023915

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4538
Approved symbol	GPR87
Name	G protein-coupled receptor 87
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138271
Ensembl biotype	protein_coding
OMIM	606379
Entrez	53836

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000260843, ENST00000629077

RefSeq mRNA: 1 — MANE Select: NM_023915 NM_023915

CCDS: CCDS3157

Canonical transcript exons

ENST00000260843 — 3 exons

Exon	Start	End
ENSE00001006050	151316586	151316820
ENSE00001076949	151300067	151300198
ENSE00001208967	151294086	151295211

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 96.87.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7494 / max 344.0583, expressed in 342 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45143	3.4337	333
45141	0.1136	43
45142	0.1019	60
45147	0.0325	7
45144	0.0268	6
45146	0.0221	5
45145	0.0189	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	96.87	gold quality
hair follicle	UBERON:0002073	95.82	gold quality
upper arm skin	UBERON:0004263	94.47	gold quality
lower esophagus mucosa	UBERON:0035834	94.23	gold quality
gingival epithelium	UBERON:0001949	93.77	gold quality
gingiva	UBERON:0001828	93.59	gold quality
esophagus mucosa	UBERON:0002469	92.86	gold quality
oral cavity	UBERON:0000167	92.08	gold quality
upper leg skin	UBERON:0004262	92.00	gold quality
skin of abdomen	UBERON:0001416	91.68	gold quality
cervix epithelium	UBERON:0004801	91.65	gold quality
mammalian vulva	UBERON:0000997	91.63	gold quality
zone of skin	UBERON:0000014	91.19	gold quality
skin of leg	UBERON:0001511	91.18	gold quality
squamous epithelium	UBERON:0006914	91.08	gold quality
esophagus squamous epithelium	UBERON:0006920	90.48	gold quality
amniotic fluid	UBERON:0000173	90.15	gold quality
epithelium of esophagus	UBERON:0001976	89.98	gold quality
epithelium of nasopharynx	UBERON:0001951	89.90	gold quality
nasopharynx	UBERON:0001728	89.88	gold quality
penis	UBERON:0000989	88.93	gold quality
palpebral conjunctiva	UBERON:0001812	88.90	gold quality
pharyngeal mucosa	UBERON:0000355	88.37	gold quality
skin of hip	UBERON:0001554	87.60	gold quality
cervix squamous epithelium	UBERON:0006922	86.18	gold quality
nasal cavity epithelium	UBERON:0005384	85.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.30	gold quality
cartilage tissue	UBERON:0002418	85.27	gold quality
mucosa of urinary bladder	UBERON:0001259	83.49	gold quality
mouth mucosa	UBERON:0003729	83.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

Literature-anchored findings (GeneRIF, showing 11)

• Results suggest that the GPR87 is a LPA receptor which evolved from a common ancestor of P2Y receptors. (PMID:17905198)
• G-protein coupled receptor(GPR87) stands out as a candidate for further target validation due to its marked overexpression and correlation on a mutation-based level to squamous cell carcinoma (PMID:18057535)
• Human GPR87 mRNA transcript was preferentially overexpressed in squamous cell carcinomas. Up-regulation of both, transcript and protein, was detected in samples of SCC of the lung, cervix, skin and head and neck (pharynx, larynx and epiglottis). (PMID:18183596)
• GPR87 knockdown sensitized cancer cells to DNA damage-induced growth suppression via enhanced p53 stabilization and activation. (PMID:19602589)
• GPR87 promotes the growth and metastasis of CD133(+) cancer stem-like cells, and our findings may reveal new targets for HCC prevention or therapy (PMID:23593389)
• This study aimed to clarify the role of GPR87 in urothelial carcinoma of the bladder. (PMID:23752273)
• knockdown of GPR87 led to a p53-dependent signal transduction and caused apoptosis in the bladder cancer cells. (PMID:26473854)
• the basal activity of GPR87 was investigated. (PMID:27865873)
• we reported that GPR87 expression was significantly upregulated in pancreatic cancer, and higher GPR87 correlated with shorter overall survival of patients with pancreatic cancer. (PMID:28288630)
• Engineering of siRNA loaded PLGA Nano-Particles for highly efficient silencing of GPR87 gene as a target for pancreatic cancer treatment. (PMID:32188321)
• Single-cell RNA sequencing identifies G-protein coupled receptor 87 as a basal cell marker expressed in distal honeycomb cysts in idiopathic pulmonary fibrosis. (PMID:35604813)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gpr87	ENSMUSG00000051431
rattus_norvegicus	Gpr87	ENSRNOG00000013894

Paralogs (6): P2RY12 (ENSG00000169313), PTAFR (ENSG00000169403), GPR34 (ENSG00000171659), P2RY14 (ENSG00000174944), GPR171 (ENSG00000174946), P2RY13 (ENSG00000181631)

Protein

Protein identifiers

G-protein coupled receptor 87 — Q9BY21 (reviewed: Q9BY21)

Alternative names: G-protein coupled receptor 95

All UniProt accessions (1): Q9BY21

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for lysophosphatidic acid (LPA). Necessary for p53/TP53-dependent survival in response to DNA damage. Promotes the Hippo-YAP signaling pathway and thereby modulates glycolysis and oxidative stress production by the regulation of hexokinase-2/HK2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in placenta and prostate. Weaker expression in thymus. Not expressed in thalamus, hippocampus, pons or cerebellum. Overexpressed in squamous cell carcinoma of the lung.

Induction. By expression of p53/TP53 and by DNA damage in a TP53-dependent manner.

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

RefSeq proteins (1): NP_076404* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR008109	P2Y13_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (23 total): topological domain 8, transmembrane region 7, glycosylation site 3, sequence variant 2, chain 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY21-F1	81.93	0.51

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): 114–192

Glycosylation sites (3): 4, 25, 33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): GOBP_G_PROTEIN_COUPLED_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, JAEGER_METASTASIS_DN, WANG_LMO4_TARGETS_DN, TGANTCA_AP1_C, GOBP_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, RYTTCCTG_ETS2_B, FUJII_YBX1_TARGETS_UP, GRADE_COLON_AND_RECTAL_CANCER_DN, NAGASHIMA_NRG1_SIGNALING_DN, GNF2_CDH3, JI_CARCINOGENESIS_BY_KRAS_AND_STK11_UP, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, CDC5_01, LIU_PROSTATE_CANCER_DN

GO Biological Process (6): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165), negative regulation of adenylate cyclase activity (GO:0007194), hippo signaling (GO:0035329), G protein-coupled purinergic nucleotide receptor signaling pathway (GO:0035589), canonical glycolysis (GO:0061621)

GO Molecular Function (2): G protein-coupled purinergic nucleotide receptor activity (GO:0045028), G protein-coupled receptor activity (GO:0004930)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor activity	2
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase activity	1
negative regulation of catalytic activity	1
regulation of adenylate cyclase activity	1
intracellular signal transduction	1
purinergic nucleotide receptor signaling pathway	1
glucokinase activity	1
glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity	1
glucose catabolic process	1
glycolytic process through glucose-6-phosphate	1
purinergic nucleotide receptor activity	1
G protein-coupled purinergic nucleotide receptor signaling pathway	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR87	ALDH18A1	P54886	728
GPR87	LPAR2	Q9HBW0	678
GPR87	LPAR3	Q9UBY5	671
GPR87	LPAR1	P78351	659
GPR87	OR56B4	Q8NH76	524
GPR87	ENPP2	Q13822	519
GPR87	GPR45	Q9Y5Y3	513
GPR87	WFDC5	Q8TCV5	508
GPR87	OR52W1	Q6IF63	498
GPR87	MED12L	Q86YW9	485
GPR87	GPR62	Q9BZJ7	473
GPR87	LMNTD1	Q8N9Z9	468
GPR87	OR56A3	Q8NH54	459
GPR87	GPR63	Q9BZJ6	455
GPR87	GPR3	P46089	454

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ERBIN	GPR87	psi-mi:“MI:0915”(physical association)	0.400
GPR87	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
GPR87	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR87	psi-mi:“MI:0915”(physical association)	0.400
GPR87	E6	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): GPR87 (PCA), GPR87 (PCA), GPR87 (PCA)

ESM2 similar proteins: B5X337, D4A4Q2, D4A7K7, O00398, O14626, O35881, P21556, P25105, P32249, P43657, P60019, Q15391, Q1RMI1, Q2NNR5, Q3SAG9, Q3SX17, Q3U507, Q3U6B2, Q3UJF0, Q3ZBK9, Q4G072, Q5ZI82, Q6XCF2, Q80Z39, Q8BFU7, Q8BG55, Q8BLG2, Q8BMC0, Q920A1, Q924T8, Q924T9, Q95KC3, Q95N02, Q95N03, Q99677, Q99JA4, Q99MT7, Q9BXC1, Q9BY21, Q9CPV9

Diamond homologs: D4A4Q2, O14626, O35881, P30992, P32250, Q15391, Q3SX17, Q3ZBK9, Q6GUG4, Q8BG55, Q95KC3, Q99MT7, Q9BE53, Q9BPV8, Q9BY21, Q9CPV9, Q9D8I2, Q9EPX4, Q9ESG6, Q9H244, O00254, P25105, Q28553, P60019, Q05394, Q3SAG9, Q6XCF2, Q9R1K6, Q9UPC5, B0UXR0, C8YUV0, E9QJ73, O02213, O08786, O09047, O16020, O42179, O55197, O57422, O70129

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

538 predictions. Top by Δscore:

Variant	Effect	Δscore
3:151295210:ATCT:A	acceptor_loss	1.0000
3:151295211:TC:T	acceptor_loss	1.0000
3:151295212:C:CC	acceptor_gain	1.0000
3:151295212:C:CG	acceptor_loss	1.0000
3:151300065:A:AC	donor_gain	1.0000
3:151300066:C:CC	donor_gain	1.0000
3:151294509:C:CA	acceptor_gain	0.9900
3:151295209:TAT:T	acceptor_gain	0.9900
3:151295213:T:G	acceptor_loss	0.9900
3:151300056:CGA:C	donor_gain	0.9900
3:151300055:A:AC	donor_gain	0.9800
3:151300056:C:CC	donor_gain	0.9800
3:151315461:T:A	donor_gain	0.9800
3:151316591:ATTGT:A	acceptor_gain	0.9800
3:151316595:T:TA	acceptor_gain	0.9800
3:151295207:GTTAT:G	acceptor_gain	0.9700
3:151295208:TTAT:T	acceptor_gain	0.9700
3:151295210:AT:A	acceptor_gain	0.9700
3:151316762:ACC:A	donor_gain	0.9700
3:151316763:CCC:C	donor_gain	0.9700
3:151300196:TTT:T	acceptor_gain	0.9600
3:151300199:C:CC	acceptor_gain	0.9600
3:151315392:G:C	donor_gain	0.9600
3:151294510:G:A	acceptor_gain	0.9500
3:151300059:CGGCT:C	donor_loss	0.9500
3:151300060:GGCTT:G	donor_loss	0.9500
3:151300061:GCTTA:G	donor_loss	0.9500
3:151300062:CT:C	donor_loss	0.9500
3:151300063:TTAC:T	donor_loss	0.9500
3:151300064:T:TG	donor_loss	0.9500

AlphaMissense

2374 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:151294838:G:C	S136R	0.999
3:151294838:G:T	S136R	0.999
3:151294840:T:G	S136R	0.999
3:151295078:G:C	S56R	0.999
3:151295078:G:T	S56R	0.999
3:151295080:T:G	S56R	0.999
3:151294314:G:T	P311Q	0.998
3:151294446:G:C	P267R	0.998
3:151294451:A:C	F265L	0.998
3:151294451:A:T	F265L	0.998
3:151294453:A:G	F265L	0.998
3:151294750:A:G	W166R	0.998
3:151294750:A:T	W166R	0.998
3:151294830:C:G	R139P	0.998
3:151294314:G:C	P311R	0.997
3:151294324:A:G	C308R	0.997
3:151294446:G:T	P267Q	0.997
3:151294849:C:G	G133R	0.997
3:151294849:C:T	G133R	0.997
3:151295007:A:G	L80P	0.997
3:151294316:A:C	D310E	0.996
3:151294316:A:T	D310E	0.996
3:151294456:A:G	C264R	0.996
3:151294463:A:C	F261L	0.996
3:151294463:A:T	F261L	0.996
3:151294465:A:G	F261L	0.996
3:151294639:A:G	W203R	0.996
3:151294639:A:T	W203R	0.996
3:151294648:C:A	G200W	0.996
3:151294986:T:G	D87A	0.996

dbSNP variants (sampled 300 via entrez): RS1000156578 (3:151310394 T>C), RS1000223751 (3:151311996 C>A,T), RS1000237872 (3:151299151 A>G), RS1000474755 (3:151317237 A>T), RS1000938900 (3:151309750 T>G), RS1000981797 (3:151304391 T>C), RS1001029511 (3:151316010 A>G), RS1001241605 (3:151316920 A>G,T), RS1001252904 (3:151316629 C>T), RS1001306796 (3:151302964 A>C,T), RS1001307234 (3:151310049 T>C), RS1001577445 (3:151314854 G>T), RS1001585326 (3:151305170 C>G,T), RS1001961336 (3:151313710 C>G,T), RS1002173034 (3:151310982 C>T)

Disease associations

OMIM: gene MIM:606379 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523915 (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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
LPA	Agonist	7.44	pEC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation, affects expression, increases expression	4
(+)-JQ1 compound	decreases expression, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression	3
sodium arsenite	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Cisplatin	increases expression, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression, increases expression	2
Cadmium Chloride	increases expression, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
chloroacetaldehyde	affects expression	1
methyleugenol	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
hydroxyhydroquinone	increases expression	1
potassium bromate	increases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
brequinar	increases expression	1
adefovir dipivoxil	increases expression	1
bazedoxifene	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
trametinib	decreases expression, affects cotreatment	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
CHEMBL4883473	Binding	PRESTO-Tango GPCRome screening (GPR87)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ZK36	Tango GPR87-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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