GPR39

Summary

GPR39 (G protein-coupled receptor 39, HGNC:4496) is a protein-coding gene on chromosome 2q21.2, encoding G-protein coupled receptor 39 (O43194). Zinc-sensing receptor that can sense changes in extracellular Zn(2+), mediate Zn(2+) signal transmission, and participates in the regulation of numerous physiological processes including glucose homeostasis regulation, gastrointestinal mobility, hormone secretion and cell death.

This gene is a member of the ghrelin receptor family and encodes a rhodopsin-type G-protein-coupled receptor (GPCR). The encoded protein is involved in zinc-dependent signaling in epithelial tissue in intestines, prostate and salivary glands. The protein may also be involved in the pathophysiology of depression.

Source: NCBI Gene 2863 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 100 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001508

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4496
Approved symbol	GPR39
Name	G protein-coupled receptor 39
Location	2q21.2
Locus type	gene with protein product
Status	Approved
Aliases	ZnR
Ensembl gene	ENSG00000183840
Ensembl biotype	protein_coding
OMIM	602886
Entrez	2863

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000329321, ENST00000470071

RefSeq mRNA: 1 — MANE Select: NM_001508 NM_001508

CCDS: CCDS2170

Canonical transcript exons

ENST00000329321 — 2 exons

Exon	Start	End
ENSE00001292865	132645101	132646582
ENSE00001315513	132416805	132417898

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 98.16.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2303 / max 73.6702, expressed in 734 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22567	1.8303	642
22565	0.2786	138
22566	0.1213	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.16	gold quality
secondary oocyte	CL:0000655	97.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.95	gold quality
sperm	CL:0000019	84.51	gold quality
ganglionic eminence	UBERON:0004023	84.23	gold quality
ventricular zone	UBERON:0003053	84.04	gold quality
right uterine tube	UBERON:0001302	81.74	gold quality
male germ cell	CL:0000015	81.60	gold quality
mucosa of transverse colon	UBERON:0004991	80.73	gold quality
adult organism	UBERON:0007023	79.87	gold quality
medial globus pallidus	UBERON:0002477	79.85	gold quality
colonic mucosa	UBERON:0000317	78.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.90	gold quality
nucleus accumbens	UBERON:0001882	77.71	gold quality
globus pallidus	UBERON:0001875	77.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	76.97	gold quality
gingival epithelium	UBERON:0001949	76.93	gold quality
lower lobe of lung	UBERON:0008949	76.74	silver quality
islet of Langerhans	UBERON:0000006	75.87	gold quality
rectum	UBERON:0001052	75.55	gold quality
bronchial epithelial cell	CL:0002328	75.07	gold quality
caudate nucleus	UBERON:0001873	74.80	gold quality
gingiva	UBERON:0001828	74.47	gold quality
jejunal mucosa	UBERON:0000399	74.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.93	gold quality
parotid gland	UBERON:0001831	73.92	gold quality
putamen	UBERON:0001874	73.30	gold quality
esophagus squamous epithelium	UBERON:0006920	73.20	silver quality
amygdala	UBERON:0001876	72.80	gold quality
mammary duct	UBERON:0001765	72.14	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.36
E-MTAB-9543	no	1.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, HNF4A, SP1

miRNA regulators (miRDB)

57 targeting GPR39, 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-513A-5P	100.00	69.77	2465
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-5001-3P	98.91	67.28	1394

Literature-anchored findings (GeneRIF, showing 39)

• ghrelin receptor, neurotensin receptor 2 and GPR39 display an unusually high degree of constitutive activity, determined by an aromatic cluster on the inner face of the extracellular ends of TMs VI and VII (PMID:15383539)
• GPR39 is probably not the obestatin receptor (PMID:16959833)
• could activate GPR39 by high concentrations of Zn(2+), demonstrating cell surface expression of a functional receptor that could elicit a Ca(2+) response. (PMID:17054911)
• GPR39 functions as a Gq-coupled Zn2+-sensing receptor (PMID:17885920)
• GPR39 protects from cell death by increasing secretion of pigment epithelium-derived growth factor (PMID:18180304)
• It is proposed that Zn2+ acts as an agonist for GPR39, not in the classical manner by directly stabilizing an active conformation of the transmembrane domain, but instead by binding to His17 and His19 in the extracellular domain. (PMID:18588883)
• Data show that Phe-V:13 can serve as an aromatic lock for the proposed active conformation of the Trp-VI:13 rotameric switch, being involved in the global movement of TM-V and TM-VI in 7TM receptor activation. (PMID:19920139)
• extracellular Zn(2+), either applied or released following injury, activates ZnR/GPR39 to promote signaling leading to epithelial repair (PMID:20522546)
• GPR39 plays an important tumorigenic role in the development and progression of esophageal squamous cell carcinoma. (PMID:21352519)
• GPR39 activation increased the expression of the anti-apoptotic protein clusterin in butyrate-treated cells. GPR39 mediates Zn2+-dependent cell growth. (PMID:22545109)
• ZnR/GPR39 is tuned to sense physiologically relevant changes in extracellular pH that regulate ZnR-dependent signaling and ion transport activity (PMID:22879599)
• GPR39 was present in thyroid autoimmune disease, non-toxic nodular goiter and toxic nodular goiter at band p51(kDa). (PMID:23485550)
• Zn(2+) -dependent activation of ZnR/GPR39 also enhances the expression of the Ca(2+) -binding protein S100A4 that is linked to invasion of prostate cancer cells. (PMID:24264723)
• Data suggests alterations (down-regulation) of the GPR39 receptor and involvement of CREB-BDNF pathway, possibly triggered by GPR39, as a new pathomechanism of depression (PMID:24333148)
• Taken together, our results provided a novel regulatory mechanism for GPR39-1b in NTRS1 signaling. (PMID:24512471)
• ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. (PMID:24967969)
• Chronic administration of many antidepressants induces GPR39 up-regulation, which suggests that the Zn(2+)-sensing receptor may be considered as a new target for drug development in the field of depression. (PMID:25490458)
• obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer. (PMID:26716511)
• data indicate that Zn(2+) acting via ZnR/GPR39 has a direct role in controlling Cl(-) absorption via upregulation of basolateral KCC1 in the colon. Moreover, colonocytic ZnR/GPR39 and KCC1 reduce water loss during diarrhea and may therefore serve as effective drug targets. (PMID:28093242)
• This study demonstrated that zinc upregulates PKCzeta by activating GPR39 to enhance the abundance of ZO-1, thereby improving epithelial integrity in S. typhimurium-infected Caco-2 cells. (PMID:28515165)
• Data suggest that expression of GPR39 undergoes Rho kinase-dependent desensitization following activation by zinc. (PMID:28619258)
• G protein-coupled receptor 39 (ZnR/GPR39) was shown to regulate the activity of ion transport mechanisms that are essential for the physiological function of epithelial and neuronal cells [Review]. (PMID:29389900)
• Enhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth (PMID:29802348)
• microRNA-1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39-mediated PI3K/AKT/mTOR pathway in HCC. (PMID:31576658)
• Zn(2+) stimulates salivary secretions via metabotropic zinc receptor ZnR/GPR39 in human salivary gland cells. (PMID:31776425)
• GPR39 Overexpression in OSCC Promotes YAP-Sustained Malignant Progression. (PMID:32325008)
• GPR39 protects against corticosterone-induced neuronal injury in hippocampal cells through the CREB-BDNF signaling pathway. (PMID:32553391)
• Orchestration of Intracellular Circuits by G Protein-Coupled Receptor 39 for Hepatitis B Virus Proliferation. (PMID:32784555)
• ZnR/GPR39 controls cell migration by orchestrating recruitment of KCC3 into protrusions, re-organization of actin and activation of MMP. (PMID:33465674)
• GPR39 promotes cardiac hypertrophy by regulating the AMPK-mTOR pathway and protein synthesis. (PMID:33554444)
• Interaction between Zinc, GPR39, BDNF and Neuropeptides in Depression. (PMID:33632103)
• Selective release of gastrointestinal hormones induced by an orally active GPR39 agonist. (PMID:33711555)
• The expression and clinical significance of GPR39 in colon cancer. (PMID:34586565)
• G protein-coupled receptor 39 alleviates mitochondrial dysfunction and hepatocyte lipid accumulation via SIRT1/Nrf2 signaling. (PMID:36525212)
• Inhibition of GPR39 restores defects in endothelial cell-mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis. (PMID:36574661)
• Signaling pathway mechanisms of neurological diseases induced by G protein-coupled receptor 39. (PMID:36942516)
• Zinc-sensing receptor activation induces endothelium-dependent hyperpolarization-mediated vasorelaxation of arterioles. (PMID:38049010)
• GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain. (PMID:38306424)
• [Expressions of zinc homeostasis proteins, GPR39 and ANO1 mRNA in the sperm of asthenozoospermia patients and their clinical significance]. (PMID:39046409)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr39	ENSDARG00000102888
mus_musculus	Gpr39	ENSMUSG00000026343
rattus_norvegicus	Gpr39	ENSRNOG00000021586

Paralogs (15): NTSR1 (ENSG00000101188), BRS3 (ENSG00000102239), MLNR (ENSG00000102539), GHSR (ENSG00000121853), GRPR (ENSG00000126010), NMUR2 (ENSG00000132911), NMBR (ENSG00000135577), EDNRB (ENSG00000136160), EDNRA (ENSG00000151617), NTSR2 (ENSG00000169006), GPR37L1 (ENSG00000170075), GPR37 (ENSG00000170775), NMUR1 (ENSG00000171596), GPR148 (ENSG00000173302), TRHR (ENSG00000174417)

Protein

Protein identifiers

G-protein coupled receptor 39 — O43194 (reviewed: O43194)

All UniProt accessions (1): O43194

UniProt curated annotations — full annotation on UniProt →

Function. Zinc-sensing receptor that can sense changes in extracellular Zn(2+), mediate Zn(2+) signal transmission, and participates in the regulation of numerous physiological processes including glucose homeostasis regulation, gastrointestinal mobility, hormone secretion and cell death. Activation by Zn(2+) in keratinocytes increases the intracellular concentration of Ca(2+) and activates the ERK/MAPK and PI3K/AKT signaling pathways leading to epithelial repair. Plays an essential role in normal wound healing by inducing the production of cytokines including the major inflammatory cytokine IL6 via the PKC/MAPK/CEBPB pathway. Regulates adipose tissue metabolism, especially lipolysis, and regulates the function of lipases, such as hormone-sensitive lipase and adipose triglyceride lipase. Plays a role in the inhibition of cell death and protects against oxidative, endoplasmic reticulum and mitochondrial stress by inducing secretion of the cytoprotective pigment epithelium-derived growth factor (PEDF) and probably other protective transcripts in a GNA13/RHOA/SRE-dependent manner. Forms dynamic heteroreceptor complexes with HTR1A and GALR1 depending on cell type or specific physiological states, resulting in signaling diversity: HTR1A-GPR39 shows additive increase in signaling along the serum response element (SRE) and NF-kappa-B pathways while GALR1 acts as an antagonist blocking SRE.

Subunit / interactions. Interacts with HTR1A. Interacts with GALR1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in many tissues, including the stomach, intestine and hypothalamus.

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

RefSeq proteins (1): NP_001499* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR052676	Zinc-sensing_GPCR	Family

Pfam: PF00001

UniProt features (33 total): topological domain 8, transmembrane region 7, mutagenesis site 4, glycosylation site 3, region of interest 2, binding site 2, disulfide bond 2, sequence variant 2, chain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43194-F1	76.53	0.52

Functional residue map

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

Ligand- & substrate-binding residues (2): 17; 19

Post-translational modifications (1): 396

Disulfide bonds (2): 11–191, 108–210

Glycosylation sites (3): 192, 206, 212

Mutagenesis-validated functional residues (4):

Position	Phenotype
17	decreases activation by zn(2+). abolishes activation by zn(2+); when associated with a-19.
19	decreases activation by zn(2+). abolishes activation by zn(2+); when associated with a-17.
312	not affect constitutive or zn(2+)-induced activation.
313	induces very high constitutive activity and eliminates zn(2+)-induced activation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-416476	G alpha (q) signalling events
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 74 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MODULE_64, MODULE_289, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, MODULE_99, RICKMAN_HEAD_AND_NECK_CANCER_C, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_UP, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, MODULE_375, KIM_BIPOLAR_DISORDER_OLIGODENDROCYTE_DENSITY_CORR_DN, FIGUEROA_AML_METHYLATION_CLUSTER_6_DN

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

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), metal ion binding (GO:0046872), protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	2
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
cation binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR39	GHRL	Q9UBU3	983
GPR39	LYPD1	Q8N2G4	890
GPR39	MLN	P12872	832
GPR39	MBOAT4	Q96T53	804
GPR39	SLC30A3	Q99726	648
GPR39	NTS	P30990	619
GPR39	PTPRN2	Q92932	588
GPR39	GHRH	P01286	559
GPR39	CPT1A	P50416	557
GPR39	GHSR	Q92847	546
GPR39	AGRP	O00253	486
GPR39	GAST	P01350	479
GPR39	SLC12A5	Q9H2X9	474
GPR39	NPY	P01303	466
GPR39	GPR139	Q6DWJ6	459

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GPR39	HTR1A	psi-mi:“MI:0403”(colocalization)	0.570
GPR39	HTR1A	psi-mi:“MI:2364”(proximity)	0.570
GPR39	HTR1A	psi-mi:“MI:0915”(physical association)	0.570
HTR1A	GPR39	psi-mi:“MI:0914”(association)	0.570
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
GSK3B	GPR39	psi-mi:“MI:0915”(physical association)	0.370
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNB1	CLGN	psi-mi:“MI:0914”(association)	0.350
HEATR3	PLD2	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
SCN3B	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC39A12	GPR39	psi-mi:“MI:0914”(association)	0.350
SLC39A4	GPR39	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): GPR39 (Affinity Capture-MS), GPR39 (Affinity Capture-MS), GPR39 (Proximity Label-MS), GPR39 (Proximity Label-MS), GPR39 (Two-hybrid)

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: A6NND4, B2ZHY2, B4XF06, E7EM37, O02664, O08858, O43194, O88319, P0C0L6, P20789, P20905, P21917, P30989, P32250, P35404, P35406, P41595, P42291, P51582, Q4G072, Q5U431, Q61H86, Q6IF99, Q6RYS9, Q6XXX8, Q8BMC0, Q8BZP8, Q8HZ64, Q8UUG8, Q923Y1, Q923Y4, O00254, O15974, P07700, P79250, Q28422, Q56H79, Q58D85, Q93126, Q96R48

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1558 predictions. Top by Δscore:

Variant	Effect	Δscore
2:132417899:G:GG	donor_gain	1.0000
2:132645084:T:TA	acceptor_gain	1.0000
2:132646127:C:A	donor_gain	1.0000
2:132417843:G:GT	donor_gain	0.9900
2:132417876:G:GT	donor_gain	0.9900
2:132417897:GA:G	donor_gain	0.9900
2:132441496:G:GT	donor_gain	0.9900
2:132490614:GCAT:G	donor_gain	0.9900
2:132490617:T:G	donor_gain	0.9900
2:132645071:T:TA	acceptor_gain	0.9900
2:132645084:T:A	acceptor_loss	0.9900
2:132645088:C:CA	acceptor_gain	0.9900
2:132645090:T:TA	acceptor_gain	0.9900
2:132645094:T:TA	acceptor_gain	0.9900
2:132645099:A:AC	acceptor_loss	0.9900
2:132645099:A:AG	acceptor_gain	0.9900
2:132645099:AG:A	acceptor_gain	0.9900
2:132645099:AGG:A	acceptor_gain	0.9900
2:132645100:G:GG	acceptor_gain	0.9900
2:132645100:GG:G	acceptor_gain	0.9900
2:132645100:GGG:G	acceptor_gain	0.9900
2:132645100:GGGC:G	acceptor_gain	0.9900
2:132645100:GGGCT:G	acceptor_gain	0.9900
2:132646126:T:TA	donor_gain	0.9900
2:132646198:C:A	donor_gain	0.9900
2:132490617:T:TG	donor_gain	0.9800
2:132644992:G:GG	donor_gain	0.9800
2:132645973:A:AC	donor_gain	0.9800
2:132645974:C:CC	donor_gain	0.9800
2:132417896:TGA:T	donor_gain	0.9600

AlphaMissense

2973 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:132417262:A:C	S74R	0.999
2:132417264:T:A	S74R	0.999
2:132417264:T:G	S74R	0.999
2:132417430:A:C	S130R	0.998
2:132417432:C:A	S130R	0.998
2:132417432:C:G	S130R	0.998
2:132645186:G:C	W314C	0.993
2:132645186:G:T	W314C	0.993
2:132645295:T:C	F351L	0.993
2:132645297:T:A	F351L	0.993
2:132645297:T:G	F351L	0.993
2:132417520:T:A	W160R	0.992
2:132417520:T:C	W160R	0.992
2:132417440:G:C	R133P	0.991
2:132645137:C:G	P298R	0.991
2:132645250:A:C	S336R	0.991
2:132645252:C:A	S336R	0.991
2:132645252:C:G	S336R	0.991
2:132645137:C:A	P298H	0.990
2:132417172:G:C	G44R	0.989
2:132417269:C:A	A76D	0.989
2:132417449:C:A	A136D	0.989
2:132417397:A:C	S119R	0.988
2:132417399:C:A	S119R	0.988
2:132417399:C:G	S119R	0.988
2:132645266:C:A	P341Q	0.988
2:132417275:C:G	S78W	0.986
2:132645127:T:C	C295R	0.986
2:132645184:T:A	W314R	0.986
2:132645184:T:C	W314R	0.986

dbSNP variants (sampled 300 via entrez): RS1000033159 (2:132493877 C>G,T), RS1000054641 (2:132620197 A>C,G), RS1000054963 (2:132617446 G>A), RS1000056405 (2:132587175 A>G), RS1000061617 (2:132459718 G>A), RS1000071876 (2:132490224 A>T), RS1000079498 (2:132580976 A>C), RS1000100825 (2:132464864 C>T), RS1000133214 (2:132625838 T>C), RS1000139011 (2:132481631 T>C), RS1000140434 (2:132443376 C>T), RS1000151695 (2:132462501 C>A,G), RS1000156125 (2:132561427 G>A,T), RS1000161846 (2:132570699 C>T), RS1000175413 (2:132434921 T>C)

Disease associations

OMIM: gene MIM:602886 | 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
GCST002911_4	Calcium levels	1.000000e-06
GCST006309_4	Post bronchodilator percent predicted FEV1 in smoking	6.000000e-06
GCST006310_2	Post bronchodilator FEV1/FVC ratio in smoking	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3091266 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 411,454 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1200679	ZINC CHLORIDE	4	411,454

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
compound 15 [PMID: 25313322]	Full agonist	9.1	pEC50
compound 1 [PMID: 24900608]	Full agonist	7.2	pEC50

ChEMBL bioactivities

127 potent at pChembl≥5 of 129 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	EC50	0.06	nM	CHEMBL3342358
9.74	EC50	0.18	nM	CHEMBL3342376
9.46	EC50	0.35	nM	CHEMBL3342379
9.26	EC50	0.55	nM	CHEMBL3342377
9.10	EC50	0.8	nM	CHEMBL3342370
9.10	EC50	0.8	nM	CHEMBL3342358
9.00	EC50	1	nM	CHEMBL3342379
9.00	EC50	1	nM	CHEMBL4072160
8.82	EC50	1.5	nM	CHEMBL4100119
8.70	EC50	2	nM	CHEMBL4083614
8.70	EC50	2	nM	CHEMBL4089047
8.70	EC50	2	nM	CHEMBL4104345
8.52	EC50	3	nM	CHEMBL3342376
8.52	EC50	3	nM	CHEMBL4099134
8.52	EC50	3	nM	CHEMBL4101617
8.52	EC50	3	nM	CHEMBL4062704
8.52	EC50	3	nM	CHEMBL4098394
8.52	EC50	3	nM	CHEMBL4071347
8.52	EC50	3	nM	CHEMBL5207240
8.44	EC50	3.6	nM	ZINC CHLORIDE
8.40	EC50	4	nM	CHEMBL4063554
8.40	EC50	4	nM	CHEMBL4091396
8.40	EC50	4	nM	CHEMBL4067834
8.40	EC50	4	nM	CHEMBL4082109
8.40	EC50	4	nM	CHEMBL4059978
8.40	EC50	4	nM	CHEMBL4080106
8.30	EC50	5	nM	CHEMBL3342377
8.30	EC50	5	nM	CHEMBL4081167
8.30	EC50	5	nM	CHEMBL4105417
8.30	EC50	5	nM	CHEMBL4090669
8.30	EC50	5	nM	CHEMBL4081885
8.22	EC50	6	nM	CHEMBL4060772
8.15	EC50	7	nM	CHEMBL4075137
8.10	EC50	8	nM	CHEMBL4104470
8.10	EC50	8	nM	CHEMBL4087979
8.05	EC50	9	nM	CHEMBL4077818
8.00	EC50	10	nM	CHEMBL4086570
8.00	EC50	10	nM	CHEMBL4068635
7.96	EC50	11	nM	CHEMBL3342366
7.96	EC50	11	nM	CHEMBL3341764
7.92	EC50	12	nM	CHEMBL4100119
7.89	EC50	13	nM	CHEMBL3342374
7.82	EC50	15	nM	CHEMBL3342367
7.82	EC50	15	nM	CHEMBL3342358
7.82	EC50	15	nM	CHEMBL5182651
7.80	EC50	16	nM	CHEMBL4096749
7.80	EC50	16	nM	CHEMBL4078723
7.80	EC50	16	nM	CHEMBL5195894
7.77	EC50	17	nM	CHEMBL4077818
7.77	EC50	17	nM	CHEMBL5177479

PubChem BioAssay actives

127 with measured affinity, of 217 total; 50 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
N-[3-chloro-4-[[[2-(methylamino)-6-pyridin-2-ylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide	1169001: Agonist activity at human GPR39 expressed in HEK293 cells by cAMP assay	ec50	0.0001	uM
N-[4-[[[2-(methylamino)-6-pyridin-2-ylpyrimidin-4-yl]amino]methyl]phenyl]methanesulfonamide	1169001: Agonist activity at human GPR39 expressed in HEK293 cells by cAMP assay	ec50	0.0002	uM
N-[3-fluoro-4-[[[2-(methylamino)-6-pyridin-2-ylpyrimidin-4-yl]amino]methyl]phenyl]acetamide	1169001: Agonist activity at human GPR39 expressed in HEK293 cells by cAMP assay	ec50	0.0003	uM
N-[4-[[[2-(methylamino)-6-pyridin-2-ylpyrimidin-4-yl]amino]methyl]phenyl]acetamide	1169001: Agonist activity at human GPR39 expressed in HEK293 cells by cAMP assay	ec50	0.0006	uM
4-N-[(2,4-dichlorophenyl)methyl]-2-N-methyl-6-pyridin-2-ylpyrimidine-2,4-diamine	1168998: Agonist activity at human GPR39 expressed in HEK293 cells by IP1 assay	ec50	0.0008	uM
4-[(4-fluorophenyl)methoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0010	uM
4-[(6-fluoro-4H-1,3-benzodioxin-8-yl)methoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0015	uM
4-[2-(4-methoxyphenyl)ethoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0020	uM
4-[(2-chlorophenyl)methoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0020	uM
4-cyclopentyloxy-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0020	uM
4-N-[(2-chlorophenyl)methyl]-2-N-methyl-6-pyridin-2-ylpyrimidine-2,4-diamine	1879220: Agonist activity at human GPR39 receptor expressed in CHO cells assessed as increase in ca2+ flux	ec50	0.0030	uM
N-[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl]benzamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0030	uM
N-[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl]-2-thiophen-2-ylacetamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0030	uM
4-[2-(4-fluorophenyl)-2-oxoethoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0030	uM
3-methyl-4-(2-phenylethoxy)-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0030	uM
N-[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl]-2-phenylacetamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0030	uM
zinc dichloride	1169001: Agonist activity at human GPR39 expressed in HEK293 cells by cAMP assay	ec50	0.0036	uM
4-[[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl]oxymethyl]benzonitrile	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0040	uM
[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl] 4-fluorobenzoate	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0040	uM
N-[(4-fluorophenyl)methyl]-3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridine-4-carboxamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0040	uM
3-methyl-4-(2-methylpropoxy)-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0040	uM
4-[(2-fluorophenyl)methoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0040	uM
4-[(2,4-dichlorophenyl)methoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0040	uM
N-[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl]-2-phenylbutanamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0050	uM
N-benzyl-3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridine-4-carboxamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0050	uM
3-methyl-4-[(4-propan-2-ylphenyl)methoxy]-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0050	uM
4-[(3,5-dimethyl-1,2-oxazol-4-yl)methoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0050	uM
[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl] 2-phenylacetate	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0060	uM
N-(1,3-benzodioxol-5-ylmethyl)-3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridine-4-carboxamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0070	uM
3-methyl-4-octoxy-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0080	uM
2-[[3-methyl-6-oxo-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-4-yl]oxymethyl]benzonitrile	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0080	uM
4-(2-chloro-4-fluorophenyl)-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0090	uM
3-methyl-6-oxo-N-phenyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridine-4-carboxamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0100	uM
3-methyl-4-[2-(5-methylpyrazol-1-yl)ethoxy]-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0100	uM
N-[[4-[[[2-(cyclopropylamino)-6-pyridin-2-ylpyrimidin-4-yl]amino]methyl]cyclohexyl]methyl]-3-fluorobenzenesulfonamide	1168993: Agonist activity at human GPR39 by IP1 assay	ec50	0.0110	uM
4-N-(cyclohexylmethyl)-2-N-methyl-6-pyridin-2-ylpyrimidine-2,4-diamine	1168998: Agonist activity at human GPR39 expressed in HEK293 cells by IP1 assay	ec50	0.0110	uM
2-N-methyl-6-pyridin-2-yl-4-N-[[4-(trifluoromethoxy)phenyl]methyl]pyrimidine-2,4-diamine	1168998: Agonist activity at human GPR39 expressed in HEK293 cells by IP1 assay	ec50	0.0130	uM
4-N-[(4-chlorophenyl)methyl]-2-N-methyl-6-pyridin-2-ylpyrimidine-2,4-diamine	1168998: Agonist activity at human GPR39 expressed in HEK293 cells by IP1 assay	ec50	0.0150	uM
N-[(4-fluorophenyl)methyl]-5-methyl-3-pyridin-2-ylpyrazolo[1,5-a]pyrimidin-7-amine	1879220: Agonist activity at human GPR39 receptor expressed in CHO cells assessed as increase in ca2+ flux	ec50	0.0150	uM
4-[2-(3,5-dimethylpyrazol-1-yl)ethoxy]-3-methyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0160	uM
3-methyl-1-(7H-purin-6-yl)-4-(2-pyrazol-1-ylethoxy)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0160	uM
4-N-cyclohexyl-2-N-methyl-6-pyridin-2-ylpyrimidine-2,4-diamine	1879220: Agonist activity at human GPR39 receptor expressed in CHO cells assessed as increase in ca2+ flux	ec50	0.0160	uM
N-[1-(4-fluorophenyl)ethyl]-5-methyl-3-pyridin-2-ylpyrazolo[1,5-a]pyrimidin-7-amine	1879220: Agonist activity at human GPR39 receptor expressed in CHO cells assessed as increase in ca2+ flux	ec50	0.0170	uM
5-methyl-7-(2-phenylpyrrolidin-1-yl)-3-pyridin-2-ylpyrazolo[1,5-a]pyrimidine	1879220: Agonist activity at human GPR39 receptor expressed in CHO cells assessed as increase in ca2+ flux	ec50	0.0170	uM
3-methyl-4-(4-propan-2-yloxyphenyl)-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridin-6-one	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0180	uM
N,3-dimethyl-6-oxo-1-(7H-purin-6-yl)-N-(1,3-thiazol-2-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridine-4-carboxamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0180	uM
N-methyl-4-phenoxy-6-pyridin-2-ylpyrimidin-2-amine	1879222: Positive allosteric activity at human GPR39 receptor expressed in CHO cells assessed as increase in zn2+ induced ca2+ flux	ec50	0.0230	uM
4-N-[1-(4-chlorophenyl)cyclobutyl]-2-N-methyl-6-pyridin-2-ylpyrimidine-2,4-diamine	1168998: Agonist activity at human GPR39 expressed in HEK293 cells by IP1 assay	ec50	0.0250	uM
N-methyl-4-[[[2-(methylamino)-6-pyridin-2-ylpyrimidin-4-yl]amino]methyl]benzamide	1168998: Agonist activity at human GPR39 expressed in HEK293 cells by IP1 assay	ec50	0.0300	uM
N,3-dimethyl-6-oxo-N-phenyl-1-(7H-purin-6-yl)-5,7-dihydro-4H-pyrazolo[5,4-b]pyridine-4-carboxamide	1428546: Agonist activity at human GPR39 expressed in HEK293 cells co-expressing Galphaq assessed as myo-[2-3H]inositol phosphate accumulation in presence of 10 uM Zn2+ measured after 75 mins by scintillation proximity assay	ec50	0.0320	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
sodium arsenite	decreases expression, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
sotorasib	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
candoxin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Calcitriol	decreases expression	1
Nickel	increases expression	1
Pesticides	decreases methylation	1
Rotenone	decreases expression	1
Thiram	decreases expression	1

ChEMBL screening assays

32 unique, capped per target: 23 functional, 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3096567	Functional	Agonist activity at GPR39 in human HT-29 cells assessed as cAMP accumulation up to 30 uM	Chemical Probe Identification Platform for Orphan GPCRs Using Focused Compound Screening: GPR39 as a Case Example. — ACS Med Chem Lett
CHEMBL3096571	Binding	Agonist activity at GPR39 in human islets assessed as 11.2 mM glucose-stimulated insulin secretion up to 10 uM after 1 hr	Chemical Probe Identification Platform for Orphan GPCRs Using Focused Compound Screening: GPR39 as a Case Example. — ACS Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7QW	Ubigene A-549 GPR39 KO	Cancer cell line	Male
CVCL_F1U1	HyCyte THP-1 KO-hGPR39	Cancer cell line	Male
CVCL_KU67	U2OS GPR39 Gq	Cancer cell line	Female
CVCL_KX62	PathHunter CHO-K1 GPR39 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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