GPR34

Summary

GPR34 (G protein-coupled receptor 34, HGNC:4490) is a protein-coding gene on chromosome Xp11.4, encoding Probable G-protein coupled receptor 34 (Q9UPC5). G-protein-coupled receptor of lysophosphatidylserine (LysoPS) that plays different roles in immune response.

G protein-coupled receptors (GPCRs), such as GPR34, are integral membrane proteins containing 7 putative transmembrane domains (TMs). These proteins mediate signals to the interior of the cell via activation of heterotrimeric G proteins that in turn activate various effector proteins, ultimately resulting in a physiologic response.

Source: NCBI Gene 2857 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001097579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4490
Approved symbol	GPR34
Name	G protein-coupled receptor 34
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	LPS1
Ensembl gene	ENSG00000171659
Ensembl biotype	protein_coding
OMIM	300241
Entrez	2857

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000378138, ENST00000378142, ENST00000649219, ENST00000884189, ENST00000956400, ENST00000956401

RefSeq mRNA: 2 — MANE Select: NM_001097579 NM_001097579, NM_005300

CCDS: CCDS14258

Canonical transcript exons

ENST00000378142 — 3 exons

Exon	Start	End
ENSE00001129048	41689743	41689835
ENSE00001476410	41695555	41697275
ENSE00001476414	41688973	41689084

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 90.79.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3217 / max 408.2957, expressed in 396 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196044	4.0344	377
196043	2.2055	278
196045	0.0818	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	90.79	gold quality
smooth muscle tissue	UBERON:0001135	88.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.72	gold quality
placenta	UBERON:0001987	87.49	gold quality
ileal mucosa	UBERON:0000331	86.36	gold quality
right coronary artery	UBERON:0001625	85.91	gold quality
vermiform appendix	UBERON:0001154	85.83	gold quality
gall bladder	UBERON:0002110	85.28	gold quality
rectum	UBERON:0001052	84.31	gold quality
monocyte	CL:0000576	83.19	gold quality
leukocyte	CL:0000738	82.91	gold quality
adipose tissue	UBERON:0001013	82.71	gold quality
descending thoracic aorta	UBERON:0002345	82.06	gold quality
left coronary artery	UBERON:0001626	82.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.74	gold quality
decidua	UBERON:0002450	81.47	gold quality
spinal cord	UBERON:0002240	81.45	gold quality
spleen	UBERON:0002106	81.37	gold quality
layer of synovial tissue	UBERON:0007616	80.81	gold quality
lymph node	UBERON:0000029	80.75	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.46	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.45	gold quality
coronary artery	UBERON:0001621	80.41	gold quality
right adrenal gland cortex	UBERON:0035827	80.28	gold quality
synovial joint	UBERON:0002217	80.22	gold quality
omental fat pad	UBERON:0010414	80.13	gold quality
peritoneum	UBERON:0002358	80.03	gold quality
left adrenal gland	UBERON:0001234	79.89	gold quality
left adrenal gland cortex	UBERON:0035825	79.86	gold quality
right adrenal gland	UBERON:0001233	79.68	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	51.49
E-HCAD-10	yes	41.20
E-GEOD-134144	yes	25.48
E-CURD-112	yes	14.44
E-ANND-3	yes	12.38
E-MTAB-6678	yes	11.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting GPR34, 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-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620

Literature-anchored findings (GeneRIF, showing 15)

• data show that multiple translation initiation starts and alternative splicing contribute to the supragenomic diversification of GPR34 (PMID:16338117)
• The present studies confirm that GPR34 is a cellular receptor for LysoPS, especially with a fatty acid at the sn-2 position. (PMID:22343749)
• these results are the first to identify a role for a GPR34 in lymphoma cell growth, provide insight into GPR34-mediated signaling, identify a genetically unique subset of MZLs that express high levels of GPR34. (PMID:22966169)
• up-regulation of GPR34 expression in human gastric carcinoma may play a critical role in tumor progression and in determining patient prognosis (PMID:23836308)
• GPR34 knockdown impairs the proliferation and migration of HGC-27 gastric cancer cells in vitro and provides a potential implication for therapy of gastric cancer. (PMID:25673461)
• By monitoring fused FLAG-tag and conformation-sensitive native epitope during expression of GPR34 mutants, a tri-basic motif in the first intracellular loop was identified as key topogenic signal that dictates the orientation of transmembrane domain-1. (PMID:27086875)
• Membrane Phospholipid Analogues as Molecular Rulers to Probe the Position of the Hydrophobic Contact Point of Lysophospholipid Ligands on the Surface of G-Protein-Coupled Receptor during Membrane Approach. (PMID:32124599)
• MicroRNA-381 targets G protein-Coupled receptor 34 (GPR34) to regulate the growth, migration and invasion of human cervical cancer cells. (PMID:33086148)
• GPR34 activation potentially bridges lymphoepithelial lesions to genesis of salivary gland MALT lymphoma. (PMID:34086889)
• G-protein coupled receptor 34 regulates the proliferation and growth of LS174T cells through differential expression of PI3K subunits and PTEN. (PMID:34997428)
• G-protein Coupled Receptor 34 Promotes Gliomagenesis by Inducing Proliferation and Malignant Phenotype via TGF-Beta/Smad Signaling Pathway. (PMID:35770303)
• Cryo-EM structures of human GPR34 enable the identification of selective antagonists. (PMID:37733739)
• Structural basis for ligand recognition and signaling of the lysophosphatidylserine receptors GPR34 and GPR174. (PMID:38048360)
• Structural basis for lysophosphatidylserine recognition by GPR34. (PMID:38326347)
• GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunity. (PMID:39358444)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr34b	ENSDARG00000002959
		ENSDARG00000098490
mus_musculus	Gpr34	ENSMUSG00000040229
rattus_norvegicus	Gpr34	ENSRNOG00000039759

Paralogs (6): GPR87 (ENSG00000138271), P2RY12 (ENSG00000169313), PTAFR (ENSG00000169403), P2RY14 (ENSG00000174944), GPR171 (ENSG00000174946), P2RY13 (ENSG00000181631)

Protein

Protein identifiers

Probable G-protein coupled receptor 34 — Q9UPC5 (reviewed: Q9UPC5)

All UniProt accessions (2): Q9UPC5, Q5VT14

UniProt curated annotations — full annotation on UniProt →

Function. G-protein-coupled receptor of lysophosphatidylserine (LysoPS) that plays different roles in immune response. Acts a damage-sensing receptor that triggers tissue repair upon recognition of dying neutrophils. Mechanistically, apoptotic neutrophils release lysophosphatydilserine that are recognized by type 3 innate lymphoid cells (ILC3s) via GPR34, which activates downstream PI3K-AKT and RAS-ERK signaling pathways leading to STAT3 activation and IL-22 production. Plays an important role in microglial function, controlling morphology and phagocytosis.

Subcellular location. Cell membrane.

Tissue specificity. Broadly expressed. Highly expressed on mast cells.

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

RefSeq proteins (2): NP_001091048, NP_005291 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR048057	GPR34_7tmA	Domain

Pfam: PF00001

UniProt features (48 total): helix 14, topological domain 8, turn 8, transmembrane region 7, glycosylation site 5, strand 3, chain 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8K4N	ELECTRON MICROSCOPY	2.83
8XBH	ELECTRON MICROSCOPY	2.83
8WRB	ELECTRON MICROSCOPY	2.91
8IZ4	ELECTRON MICROSCOPY	2.93
8XBI	ELECTRON MICROSCOPY	3.06
8SAI	ELECTRON MICROSCOPY	3.27
8IYX	ELECTRON MICROSCOPY	3.34
8XBE	ELECTRON MICROSCOPY	3.4
8XBG	ELECTRON MICROSCOPY	3.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPC5-F1	77.74	0.47

Antibody-complex structures (SAbDab): 6 — 8IZ4, 8K4N, 8SAI, 8WRB, 8XBE, 8XBH

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): 127–204

Glycosylation sites (5): 28, 36, 42, 200, 295

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GOBP_G_PROTEIN_COUPLED_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, CAGCTG_AP4_Q5, RYTAAWNNNTGAY_UNKNOWN, GOBP_PURINERGIC_NUCLEOTIDE_RECEPTOR_SIGNALING_PATHWAY, GAVIN_FOXP3_TARGETS_CLUSTER_P3, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, MATSUDA_NATURAL_KILLER_DIFFERENTIATION, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_DN, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, LI_INDUCED_T_TO_NATURAL_KILLER_UP, chrXp11, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOMF_NUCLEOTIDE_RECEPTOR_ACTIVITY, STK33_SKM_UP, STK33_UP

GO Biological Process (3): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165), G protein-coupled purinergic nucleotide receptor signaling pathway (GO:0035589)

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

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
purinergic nucleotide receptor signaling pathway	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
purinergic nucleotide receptor activity	1
G protein-coupled purinergic nucleotide receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR34	EFHC2	Q5JST6	846
GPR34	TMEM119	Q4V9L6	732
GPR34	OLFML3	Q9NRN5	678
GPR34	TREM2	Q9NZC2	619
GPR34	C1QA	P02745	519
GPR34	SALL1	Q9NSC2	515
GPR34	UBA1	P22314	509
GPR34	PROS1	P07225	485
GPR34	MERTK	Q12866	479
GPR34	CSF1R	P07333	468
GPR34	AIF1	P55008	449
GPR34	ADORA3	P0DMS8	422
GPR34	SLC2A5	P22732	414
GPR34	GAS6	Q14393	397
GPR34	TYROBP	O43914	392

IntAct

11 interactions, top by confidence:

A	B	Type	Score
RAMP2	GPR34	psi-mi:“MI:0915”(physical association)	0.400
GPR34	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR34	psi-mi:“MI:0915”(physical association)	0.400
GPR34	COX7A2L	psi-mi:“MI:0914”(association)	0.350
GPR34	NDUFC2	psi-mi:“MI:0914”(association)	0.350
GPR34		psi-mi:“MI:0915”(physical association)	0.000
GPR34	aspC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): NDUFB1 (Affinity Capture-MS), TNFRSF10D (Affinity Capture-MS), COX7A2L (Affinity Capture-MS), XPO4 (Affinity Capture-MS), TMED8 (Affinity Capture-MS), NDUFC2 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NDUFB5 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), ND5 (Affinity Capture-MS), NDUFB3 (Affinity Capture-MS), NDUFS4 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), GPR34 (Negative Genetic)

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: A0A287A2K5, A5A4K9, A5A4L1, C8YUV0, O08725, O88634, P25024, P25025, P30552, P30553, P30796, P46627, P49683, P55919, P55920, P56481, P60019, P70310, P70612, P79266, Q15077, Q28422, Q28519, Q28807, Q2AC31, Q2YEG0, Q3SAG9, Q4EW11, Q5NUL3, Q5QD06, Q5QD07, Q61H86, Q6XCF2, Q7TMA4, Q810W6, Q91ZZ5, Q920E0, Q923X9, Q92847, Q95254

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
GPR34	“up-regulates activity”	GNAI1	binding
GPR34	“up-regulates activity”	GNAI3	binding
GPR34	“up-regulates activity”	GNAO1	binding
“lysophosphatidylserine 14:0(1-)”	“up-regulates activity”	GPR34	“chemical activation”
hsa-miR-381-5p	“down-regulates quantity by repression”	GPR34	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3245351	NC_000023.10:g.(?41437573)(41712500_?)dup	Likely pathogenic

SpliceAI

562 predictions. Top by Δscore:

Variant	Effect	Δscore
X:41689080:GAACT:G	donor_gain	1.0000
X:41689082:ACT:A	donor_gain	1.0000
X:41689083:CT:C	donor_gain	1.0000
X:41689085:G:GG	donor_gain	1.0000
X:41689742:GCA:G	acceptor_gain	1.0000
X:41689041:G:T	donor_gain	0.9900
X:41689081:AACT:A	donor_gain	0.9900
X:41689086:TGAG:T	donor_loss	0.9900
X:41689087:GAGTA:G	donor_loss	0.9900
X:41689738:T:G	acceptor_gain	0.9900
X:41689741:A:AG	acceptor_gain	0.9900
X:41689742:G:GG	acceptor_gain	0.9900
X:41689742:GC:G	acceptor_gain	0.9900
X:41691234:TCTAG:T	donor_gain	0.9900
X:41689737:A:AG	acceptor_gain	0.9800
X:41689739:A:AG	acceptor_gain	0.9800
X:41689740:C:G	acceptor_gain	0.9800
X:41689742:GCAGT:G	acceptor_gain	0.9800
X:41689088:A:AG	donor_gain	0.9700
X:41689089:G:GG	donor_gain	0.9700
X:41689738:TACAG:T	acceptor_loss	0.9700
X:41689739:ACAG:A	acceptor_loss	0.9700
X:41689740:CA:C	acceptor_loss	0.9700
X:41689742:G:A	acceptor_loss	0.9700
X:41689835:GGTA:G	donor_loss	0.9700
X:41689836:GT:G	donor_loss	0.9700
X:41689837:TATG:T	donor_loss	0.9700
X:41689041:G:GT	donor_gain	0.9600
X:41689838:AT:A	donor_loss	0.9600
X:41691265:T:TA	donor_gain	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000756087 (X:41688382 T>C), RS1000860910 (X:41696087 C>T), RS1000910282 (X:41695460 C>T), RS1001195484 (X:41693411 C>G,T), RS1001246537 (X:41693084 C>T), RS1001752975 (X:41696977 C>T), RS1002762726 (X:41693714 G>A), RS1002815410 (X:41693289 A>G), RS1002867635 (X:41691447 G>T), RS1003204793 (X:41689458 T>C), RS1003260319 (X:41688818 G>A,C), RS1003737495 (X:41693830 A>C,G), RS1004677277 (X:41689821 A>G), RS1004884980 (X:41687060 A>C), RS1005039977 (X:41697230 T>C)

Disease associations

OMIM: gene MIM:300241 | 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): CHEMBL3562165 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
YL-365	Antagonist	7.77	pIC50
lysophosphatidylserine	Full agonist	6.89	pEC50

ChEMBL bioactivities

61 potent at pChembl≥5 of 64 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.12	EC50	0.75	nM	CHEMBL4753103
9.12	EC50	0.7586	nM	CHEMBL4753103
7.87	EC50	13.49	nM	CHEMBL4758243
7.85	EC50	14	nM	CHEMBL4758243
7.83	EC50	14.79	nM	CHEMBL4095241
7.82	EC50	15	nM	CHEMBL4095241
7.57	EC50	27	nM	CHEMBL4096239
7.57	EC50	26.92	nM	CHEMBL4096239
7.39	EC50	41	nM	CHEMBL4098603
7.39	EC50	40.74	nM	CHEMBL4098603
7.23	IC50	59	nM	CHEMBL5597460
7.11	EC50	78	nM	CHEMBL4090880
7.11	EC50	77.62	nM	CHEMBL4090880
7.05	EC50	90	nM	CHEMBL4072692
7.02	EC50	95.5	nM	CHEMBL4072692
6.82	EC50	150	nM	CHEMBL3814092
6.82	EC50	151.4	nM	CHEMBL3814092
6.80	EC50	160	nM	CHEMBL3577175
6.80	EC50	158.5	nM	CHEMBL3577175
6.75	EC50	180	nM	CHEMBL4084094
6.74	EC50	182	nM	CHEMBL4084094
6.64	EC50	230	nM	CHEMBL4068969
6.64	EC50	229.1	nM	CHEMBL4068969
6.63	EC50	234.4	nM	CHEMBL3577174
6.62	EC50	240	nM	CHEMBL3577174
6.61	EC50	245.5	nM	CHEMBL1742484
6.60	EC50	250	nM	CHEMBL1742484
6.54	EC50	290	nM	CHEMBL3577145
6.54	EC50	288.4	nM	CHEMBL3577145
6.53	EC50	295.1	nM	CHEMBL4089962
6.52	EC50	300	nM	CHEMBL4089962
6.50	EC50	320	nM	CHEMBL3577140
6.50	EC50	316.2	nM	CHEMBL3577140
6.39	EC50	410	nM	CHEMBL3577138
6.38	EC50	416.9	nM	CHEMBL3577138
6.34	EC50	460	nM	CHEMBL3577171
6.34	EC50	457.1	nM	CHEMBL3577171
6.26	EC50	550	nM	CHEMBL1742484
6.26	EC50	549.5	nM	CHEMBL1742484
6.17	IC50	680	nM	CHEMBL5597460
6.16	EC50	700	nM	CHEMBL3577151
6.15	EC50	708	nM	CHEMBL3577151
6.08	EC50	840	nM	CHEMBL3577147
6.08	EC50	831.8	nM	CHEMBL3577147
6.03	EC50	930	nM	CHEMBL3577170
6.03	EC50	940	nM	CHEMBL3577182
6.03	EC50	933.2	nM	CHEMBL3577170
6.03	EC50	933.2	nM	CHEMBL3577182
6.01	IC50	968	nM	CHEMBL5590919
5.89	IC50	1282	nM	CHEMBL5596866

PubChem BioAssay actives

62 with measured affinity, of 145 total; 32 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-amino-3-[hydroxy-[(3R,4R)-4-[3-(2-undecoxyphenyl)propanoyloxy]oxan-3-yl]oxyphosphoryl]oxypropanoic acid	1723463: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis	ec50	0.0008	uM
(2S)-2-amino-3-[[(2R)-1-ethoxy-3-[3-[2-[(3-phenoxyphenyl)methoxy]phenyl]propanoyloxy]propan-2-yl]oxy-hydroxyphosphoryl]oxypropanoic acid	1723463: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis	ec50	0.0135	uM
(2S)-2-amino-3-[3-[3-[2-[[3-[4-(3-tert-butylphenyl)phenoxy]phenyl]methoxy]phenyl]propanoyloxy]propoxy-hydroxyphosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.0148	uM
(2S)-2-amino-3-[hydroxy-[3-[3-[2-[[3-(4-methylphenoxy)phenyl]methoxy]phenyl]propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.0269	uM
(2S)-2-amino-3-[hydroxy-[3-[3-[2-[[3-[4-(4-phenylphenyl)phenoxy]phenyl]methoxy]phenyl]propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.0407	uM
(2S)-2-[[2-[4-(3-chlorophenyl)phenoxy]acetyl]amino]-3-(4-phenylmethoxyphenyl)propanoic acid	2118860: Antagonist activity at GPR34 (unknown origin) by Tango assay	ic50	0.0590	uM
(2S)-2-amino-3-[hydroxy-[3-[3-[2-[[3-(4-phenylphenoxy)phenyl]methoxy]phenyl]propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.0776	uM
(2S)-2-amino-3-[hydroxy-[3-[3-[2-[(3-phenoxyphenyl)methoxy]phenyl]propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.0900	uM
(2S)-2-amino-3-[hydroxy-[(2R,3R)-2-[3-[2-[(3-phenoxyphenyl)methoxy]phenyl]propanoyloxymethyl]oxan-3-yl]oxyphosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.1500	uM
(2S)-2-amino-3-[hydroxy-[(2R)-2-hydroxy-3-[3-(3-pentadecoxyphenyl)propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.1585	uM
(2S)-2-amino-3-[hydroxy-[3-[3-[2-[[3-(2-methylphenoxy)phenyl]methoxy]phenyl]propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.1800	uM
(2S)-2-amino-3-[hydroxy-[3-[3-[2-[[3-(3-methylphenoxy)phenyl]methoxy]phenyl]propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.2291	uM
(2S)-2-amino-3-[hydroxy-[(2R)-2-hydroxy-3-[3-(2-pentadecoxyphenyl)propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.2344	uM
(2S)-2-amino-3-[hydroxy-[(2R)-2-hydroxy-3-[(Z)-octadec-9-enoyl]oxypropoxy]phosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.2455	uM
(2S)-2-amino-3-[[(2R)-3-hexadecanoyloxy-2-hydroxypropoxy]-hydroxyphosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.2884	uM
(2S)-2-amino-3-[3-[3-[2-[[3-(4-tert-butylphenoxy)phenyl]methoxy]phenyl]propanoyloxy]propoxy-hydroxyphosphoryl]oxypropanoic acid	1446542: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr	ec50	0.2951	uM
(2S)-2-amino-3-[[2,2-dimethyl-3-[(Z)-octadec-9-enoyl]oxypropoxy]-hydroxyphosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.3162	uM
(2S)-2-amino-3-[hydroxy-[(2S)-2-hydroxy-3-[(Z)-octadec-9-enoyl]oxypropoxy]phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.4100	uM
(2S)-2-amino-3-[hydroxy-[(2R)-2-hydroxy-3-[3-(2-undecoxyphenyl)propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.4571	uM
(2S)-2-amino-3-[hydroxy(3-tetradecanoyloxypropoxy)phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.7000	uM
(2S)-2-amino-3-[[(2R)-3-dodecanoyloxy-2-hydroxypropoxy]-hydroxyphosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.8318	uM
(2S)-2-amino-3-[hydroxy-[(2R)-2-hydroxy-3-[3-(2-nonoxyphenyl)propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.9300	uM
(2S)-2-amino-3-[[(2R)-2-fluoro-3-[3-(2-undecoxyphenyl)propanoyloxy]propoxy]-hydroxyphosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	0.9333	uM
(2S)-2-[[2-[4-(4-fluorophenyl)phenoxy]acetyl]amino]-3-(4-phenylmethoxyphenyl)propanoic acid	2118859: Antagonist activity at GPR34 (unknown origin) by Glosensor cAMP assay	ic50	0.9680	uM
(2S)-2-[[2-[4-(3-fluorophenyl)phenoxy]acetyl]amino]-3-(4-phenylmethoxyphenyl)propanoic acid	2118859: Antagonist activity at GPR34 (unknown origin) by Glosensor cAMP assay	ic50	1.2820	uM
(2S)-3-(4-phenylmethoxyphenyl)-2-[[2-[4-[3-(trifluoromethyl)phenyl]phenoxy]acetyl]amino]propanoic acid	2118859: Antagonist activity at GPR34 (unknown origin) by Glosensor cAMP assay	ic50	1.3060	uM
(2S)-2-amino-3-[[(2R)-3-[(Z)-hexadec-9-enoyl]oxy-2-hydroxypropoxy]-hydroxyphosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	1.3490	uM
(2S)-2-[[2-[4-(4-chlorophenyl)phenoxy]acetyl]amino]-3-(4-phenylmethoxyphenyl)propanoic acid	2118859: Antagonist activity at GPR34 (unknown origin) by Glosensor cAMP assay	ic50	1.5680	uM
(2S)-2-amino-3-[hydroxy(3-octadecanoyloxypropoxy)phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	1.6596	uM
(2S)-2-amino-3-[hydroxy-[3-[3-(2-nonoxyphenyl)propanoyloxy]propoxy]phosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	1.8000	uM
(2R)-2-[[2-[4-(3-chlorophenyl)phenoxy]acetyl]amino]-3-(4-phenylmethoxyphenyl)propanoic acid	2118859: Antagonist activity at GPR34 (unknown origin) by Glosensor cAMP assay	ic50	2.9750	uM
(2S)-2-amino-3-[3-[(Z)-hexadec-9-enoyl]oxypropoxy-hydroxyphosphoryl]oxypropanoic acid	1226967: Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	ec50	3.1000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	2
Benzo(a)pyrene	decreases methylation, decreases expression	2
GSK-J4	decreases expression	1
bisphenol A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
Decitabine	affects expression	1
Air Pollutants	affects expression, increases abundance	1
Hydrogen Peroxide	increases expression	1
Iron	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Ozone	increases abundance, affects expression	1
Tretinoin	increases expression	1
Medroxyprogesterone Acetate	increases expression	1

ChEMBL screening assays

13 unique, capped per target: 8 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3579719	Binding	Agonist activity at GPR34 (unknown origin) transfected in HEK293A cells after 1 hr by TGFalpha shedding assay	Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174. — J Med Chem
CHEMBL3721014	Functional	Antagonist activity against human lung GPR34 expressed in CHO cells co-expressing Galpha116 assessed as inhibition of lysophosphatidyl serine-induced increase in intracellular calcium level pre-incubated before lysophosphatidyl serine addit	Regulating agent of GPR34 receptor function

Clinical trials (associated diseases)

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