GPR35

Summary

GPR35 (G protein-coupled receptor 35, HGNC:4492) is a protein-coding gene on chromosome 2q37.3, encoding G-protein coupled receptor 35 (Q9HC97). G-protein coupled receptor that binds to several ligands including the tryptophan metabolite kynurenic acid (KYNA), lysophosphatidic acid (LPA) or 5-hydroxyindoleacetic acid (5-HIAA) with high affinity, leading to rapid and transient activation of numerous intracellular signalin….

Enables C-X-C chemokine receptor activity. Involved in chemokine-mediated signaling pathway; negative regulation of voltage-gated calcium channel activity; and positive regulation of cytosolic calcium ion concentration. Located in plasma membrane.

Source: NCBI Gene 2859 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 97 total
• Phenotypes (HPO): 55
• Druggable target: yes — 30 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005301

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4492
Approved symbol	GPR35
Name	G protein-coupled receptor 35
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178623
Ensembl biotype	protein_coding
OMIM	602646
Entrez	2859

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000319838, ENST00000403859, ENST00000407714, ENST00000430267, ENST00000438013, ENST00000896970, ENST00000954246, ENST00000954247, ENST00000954248, ENST00000954249, ENST00000954250, ENST00000954251

RefSeq mRNA: 4 — MANE Select: NM_005301 NM_001195381, NM_001195382, NM_001394730, NM_005301

CCDS: CCDS2541, CCDS56174

Canonical transcript exons

ENST00000407714 — 2 exons

Exon	Start	End
ENSE00001553009	240625480	240625568
ENSE00002253848	240629949	240633159

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 95.04.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7686 / max 257.2801, expressed in 400 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26440	2.6249	290
26434	1.2263	73
26438	0.5128	171
26435	0.1741	35
26441	0.1003	54
26439	0.0794	34
26433	0.0509	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.04	gold quality
ileal mucosa	UBERON:0000331	91.33	gold quality
duodenum	UBERON:0002114	88.48	gold quality
transverse colon	UBERON:0001157	88.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.86	gold quality
small intestine	UBERON:0002108	86.50	gold quality
jejunal mucosa	UBERON:0000399	86.13	gold quality
type B pancreatic cell	CL:0000169	85.84	gold quality
olfactory bulb	UBERON:0002264	85.45	gold quality
granulocyte	CL:0000094	84.96	gold quality
right uterine tube	UBERON:0001302	84.56	gold quality
monocyte	CL:0000576	84.37	gold quality
mononuclear cell	CL:0000842	84.35	gold quality
leukocyte	CL:0000738	84.24	gold quality
rectum	UBERON:0001052	84.17	gold quality
intestine	UBERON:0000160	82.37	gold quality
colonic mucosa	UBERON:0000317	81.71	gold quality
colon	UBERON:0001155	81.42	gold quality
large intestine	UBERON:0000059	81.35	gold quality
pancreatic ductal cell	CL:0002079	80.34	silver quality
body of stomach	UBERON:0001161	80.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.93	gold quality
spleen	UBERON:0002106	77.49	gold quality
jejunum	UBERON:0002115	77.42	gold quality
stomach	UBERON:0000945	77.10	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.64	gold quality
blood	UBERON:0000178	76.61	gold quality
sigmoid colon	UBERON:0001159	76.01	gold quality
mucosa of stomach	UBERON:0001199	76.01	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.65
E-MTAB-6075	no	117.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

18 targeting GPR35, 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-4487	99.96	64.58	1252
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-301A-5P	96.88	68.07	931
HSA-MIR-301B-5P	96.88	67.75	946
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-3174	94.63	63.64	577

Literature-anchored findings (GeneRIF, showing 27)

• The results of the study demonstrate the coupling of GPR35 to endogenous G proteins that modulate neuronal Ca2+ channel and thereby provide evidence for a potential role of GPR35 in regulating neuronal excitability and synaptic transmission (PMID:17940199)
• These results strongly suggest that 2-acyl lysophosphatidic acid is an endogenous ligand for GPR35. (PMID:20361937)
• human iNKT cells express GPR35 functionally active in reducing IL-4 release. (PMID:20599711)
• screening assays used to identification of small MW agonists; some compounds are species-specific agonists; agonists/ligands include zaprinast, cromolyn & dicumarol (PMID:20919992)
• This review presents a summary of what is known about the G-protein coupled receptors GPR35 and GPR55 and their potential characterization as lysophospholipid or cannabinoid receptors, respectively–{REVIEW} (PMID:22820167)
• GPR35 shows associations in both ulcerative colitis (UC) and primary sclerosing cholangitis (PSC), whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis. (PMID:22821403)
• results clearly show that R4.60, R(164), R(167), and R6.58 play crucial roles in the agonist initiated activation of GPR35. (PMID:24347166)
• This article shows that GPR35 is the receptor of CXCL17. (PMID:25411203)
• Single-nucleotide polymorphism in GPR35 gene is associated with Crohn’s disease. (PMID:25489960)
• Small molecules that stimulate or block GPR35 activity can modulate vascular proliferation and migration. (PMID:27064272)
• We performed a label-free kinome short hairpin RNA screen and identified a putative signaling network of GPR35 in HT-29 cells, some of which was validated using gene expression, biochemical and cellular assays. The results showed that GPR35 induced hypoxia-inducible factor 1alpha, and was involved in synaptic transmission, sensory perception, the immune system, and morphogenetic processes. (PMID:28425521)
• GPR35 interacts with CXCL17 in breast cancer cells. (PMID:28943434)
• Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients (PMID:28961156)
• The histology of colon sections from GPR35(-/-) mice with dextran sulfate sodium-induced colitis showed extensive pathological changes including submucosal edema, diffuse ulcerations, and evidence of complete loss of crypts compared to wild-type mice with DSS-induced colitis. (PMID:30043283)
• Immunoreactivity for GPR35 was detected in normal corneas, keratoconus and Fuchs’ dystrophy, mainly in the corneal epithelium and endothelium. In corneas with Fuchs’ dystrophy, less intensive immunoreactivity for GPR35 in endothelium was revealed. (PMID:30445046)
• high level expression of G protein-coupled receptor 35 V2/3 mRNA in regional lymph nodes of colon cancer patients is a sign of poor prognosis. (PMID:31250711)
• Activation of the G-protein coupled receptor GPR35 by human milk oligosaccharides through different pathways. (PMID:32999316)
• Inflammatory bowel disease susceptible gene GPR35 promotes bowel inflammation in mice. (PMID:33724219)
• GPR35 regulates osteogenesis via the Wnt/GSK3beta/beta-catenin signaling pathway. (PMID:33839412)
• GPR35 in Intestinal Diseases: From Risk Gene to Function. (PMID:34790192)
• Expression and clinical significance of CXCL17 and GPR35 in endometrial carcinoma. (PMID:35276691)
• The GPR35 expression pattern is associated with overall survival in male patients with colorectal cancer. (PMID:35622222)
• Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists. (PMID:35926043)
• Involvement of CXCL17 and GPR35 in Gastric Cancer Initiation and Progression. (PMID:36614059)
• Increased GPR35 expression in human colorectal and pancreatic cancer samples: A preliminary clinical validation of a new biomarker. (PMID:36637186)
• Recent advances in GPR35 pharmacology; 5-HIAA serotonin metabolite becomes a ligand. (PMID:37227682)
• GPR35 acts a dual role and therapeutic target in inflammation. (PMID:38035084)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr35.1	ENSDARG00000074633
danio_rerio		ENSDARG00000113303
mus_musculus	Gpr35	ENSMUSG00000026271
rattus_norvegicus	Gpr35	ENSRNOG00000062887

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

G-protein coupled receptor 35 — Q9HC97 (reviewed: Q9HC97)

Alternative names: Kynurenic acid receptor

All UniProt accessions (1): Q9HC97

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor that binds to several ligands including the tryptophan metabolite kynurenic acid (KYNA), lysophosphatidic acid (LPA) or 5-hydroxyindoleacetic acid (5-HIAA) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. GPR35 can couple with G(i)/G(o)- or G(12)/G(13) classes of G alpha proteins depending on the context, mediating the inhibition of adenylate cyclase or activation Rho small GTPases, respectively. KYNA-binding promotes monocyte adhesion to vascular endothelium under flow conditions, leading to G(i)/GNAI1 activation and inhibition of adenylate cyclase. Involved in cardioprotection during ischemia by promoting mitochondrial remodeling: following KYNA-binding and G(i)/GNAI1 activation, GPR35 is internalized to the outer mitochondrial membrane, where it inhibits mitochondrial adenylate cyclase (ADCY10), allowing ATPIF1 to repress ATP synthase activity. Stimulates lipid metabolism, thermogenic and anti-inflammatory gene expression in adipose tissue once activated by KYNA. Plays a role in neutrophil recruitment to sites of inflammation and bacterial clearance through the major serotonin metabolite 5-HIAA that acts as a physiological ligand. In macrophages, activation by lysophosphatidic acid promotes GPR35-induced signaling with a distinct transcriptional profile characterized by TNF production associated with ERK and NF-kappa-B activation. In turn, induces chemotaxis of macrophages.

Subunit / interactions. Interacts with ARRB2.

Subcellular location. Cell membrane. Mitochondrion outer membrane.

Tissue specificity. Predominantly expressed in immune and gastrointestinal tissues.

Post-translational modifications. Multiply phosphorylated in clusters of serines and threonines in the C-terminal tail. Phosphorylation of Ser-300 and Ser-303 is mediated by GRK5 and/or GRK6.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HC97-1	1	yes
Q9HC97-2	2

RefSeq proteins (4): NP_001182310, NP_001182311, NP_001381659, NP_005292* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR044734	GPR35_7tmA	Domain

Pfam: PF00001

UniProt features (62 total): mutagenesis site 12, helix 11, topological domain 8, transmembrane region 7, sequence variant 7, modified residue 5, turn 5, sequence conflict 2, chain 1, glycosylation site 1, disulfide bond 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8H8J	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC97-F1	84.62	0.51

Antibody-complex structures (SAbDab): 1 — 8H8J

Functional residue map

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

Post-translational modifications (5): 287, 294, 300, 303, 307

Disulfide bonds (1): 89–162

Glycosylation sites (1): 2

Mutagenesis-validated functional residues (12):

Position	Phenotype
20	does not affect g-protein coupled receptor signaling in response to ligand-binding.
81	does not affect g-protein coupled receptor signaling in response to ligand-binding.
100	impaired g-protein coupled receptor signaling in response to ligand-binding.
151	impaired g-protein coupled receptor signaling in response to ligand-binding.
164	impaired g-protein coupled receptor signaling in response to ligand-binding.
167	impaired g-protein coupled receptor signaling in response to ligand-binding.
240	impaired g-protein coupled receptor signaling in response to ligand-binding.
263	does not affect g-protein coupled receptor signaling in response to ligand-binding.
287	about 40% loss of arrb2 recruitment.
300	about 50% loss of arrb2 recruitment.
303	almost complete loss of arrb2 recruitment.
307	about 75% loss of arrb2 recruitment.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)

MSigDB gene sets: 359 (showing top): MORF_RAGE, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_VOLTAGE_GATED_CALCIUM_CHANNEL_ACTIVITY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_CELL_CELL_ADHESION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_TAXIS

GO Biological Process (12): monocyte chemotaxis (GO:0002548), response to ischemia (GO:0002931), cytoskeleton organization (GO:0007010), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), positive regulation of cytosolic calcium ion concentration (GO:0007204), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), neutrophil chemotaxis (GO:0030593), leukocyte adhesion to vascular endothelial cell (GO:0061756), chemokine-mediated signaling pathway (GO:0070098), negative regulation of voltage-gated calcium channel activity (GO:1901386), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), chemokine receptor activity (GO:0004950), C-X-C chemokine receptor activity (GO:0016494)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
response to stress	1
organelle organization	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
regulation of biological quality	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
granulocyte chemotaxis	1
neutrophil migration	1
leukocyte cell-cell adhesion	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
voltage-gated calcium channel activity	1
negative regulation of calcium ion transmembrane transporter activity	1
regulation of voltage-gated calcium channel activity	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 chemoattractant receptor activity	1
cytokine receptor activity	1
chemokine binding	1
chemokine-mediated signaling pathway	1
chemokine receptor activity	1
C-X-C chemokine binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR35	CXCL17	Q6UXB2	962
GPR35	CAPN10	Q9HC96	837
GPR35	AADAT	Q8N5Z0	662
GPR35	GPR142	Q7Z601	649
GPR35	KYAT1	Q16773	627
GPR35	KMO	O15229	585
GPR35	TDO2	P48775	575
GPR35	HDAC4	P56524	555
GPR35	KYAT3	Q6YP21	553
GPR35	IDO2	Q6ZQW0	544
GPR35	RNPEPL1	Q9HAU8	537
GPR35	KYNU	Q16719	534
GPR35	FFAR4	Q5NUL3	525
GPR35	IDO1	P14902	511
GPR35	CASR	P41180	507

IntAct

63 interactions, top by confidence:

A	B	Type	Score
AUP1	GPR35	psi-mi:“MI:0915”(physical association)	0.550
RTN3	GPR35	psi-mi:“MI:0915”(physical association)	0.550
MSMO1	GPR35	psi-mi:“MI:0915”(physical association)	0.550
SYNGR2	GPR35	psi-mi:“MI:0915”(physical association)	0.550
TMEM161A	GPR35	psi-mi:“MI:0915”(physical association)	0.550
YIF1B	GPR35	psi-mi:“MI:0915”(physical association)	0.550
GPR35	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
GPR35	LGALS3	psi-mi:“MI:0914”(association)	0.530
ABHD14A	GPR35	psi-mi:“MI:0915”(physical association)	0.370
AIG1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
APH1A	GPR35	psi-mi:“MI:0915”(physical association)	0.370
ATP2C1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
ATP1A1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
BNIP1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
B3GAT3	GPR35	psi-mi:“MI:0915”(physical association)	0.370
ADGRB1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
CANX	GPR35	psi-mi:“MI:0915”(physical association)	0.370
CD81	GPR35	psi-mi:“MI:0915”(physical association)	0.370
CH25H	GPR35	psi-mi:“MI:0915”(physical association)	0.370
CMTM3	GPR35	psi-mi:“MI:0915”(physical association)	0.370
CRHR2	GPR35	psi-mi:“MI:0915”(physical association)	0.370
OSTC	GPR35	psi-mi:“MI:0915”(physical association)	0.370
ERGIC3	GPR35	psi-mi:“MI:0915”(physical association)	0.370
FTH1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
FLRT1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
GPR146	GPR35	psi-mi:“MI:0915”(physical association)	0.370
GPR161	GPR35	psi-mi:“MI:0915”(physical association)	0.370
GJC2	GPR35	psi-mi:“MI:0915”(physical association)	0.370
GHITM	GPR35	psi-mi:“MI:0915”(physical association)	0.370
KDELR1	GPR35	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (146): POTEE (Affinity Capture-MS), YES1 (Affinity Capture-MS), KTI12 (Affinity Capture-MS), GNAO1 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), POTEE (Affinity Capture-MS), ATPIF1 (Affinity Capture-MS), KTI12 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ABHD14A (Two-hybrid), AUP1 (Two-hybrid), AIG1 (Two-hybrid), APH1A (Two-hybrid), ATP2C1 (Two-hybrid)

ESM2 similar proteins: A7YY44, B0UXR0, B2GV46, E7FEL0, F8VQN3, O00398, O00590, O08707, O09027, O14843, O15529, O15552, O46685, P21556, P25105, P46002, P46093, P46094, P50132, P56484, Q00991, Q09QM4, Q13304, Q15743, Q1JQB3, Q3U507, Q3UFD7, Q3UJF0, Q4KLH9, Q6NS65, Q76EI6, Q86VZ1, Q8BFQ3, Q8BFU7, Q8BUD0, Q8BYC4, Q8C131, Q8TDS4, Q8TDS5, Q8VCK6

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, B2GV46, B5X337, D4A7K7, E7FEL0, E9QJ73, F8VQN3, O00270, O08726, O08858, O14842, O14843, O15529, O42179, O43603, O46685, O60755, O77408, O88410, O88626, O88634, O88853, P21109, P23944, P25024, P25025, P35344, P35383, P35414, P41231, P41232, P46092, P46093, P49652, P49682, P49683, P50132, P51675, P51679

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
GPR35	“up-regulates activity”	GNAI1	binding
GPR35	“up-regulates activity”	GNAI3	binding
GPR35	“up-regulates activity”	GNAO1	binding
GPR35	“up-regulates activity”	GNAZ	binding
GPR35	“up-regulates activity”	GNA12	binding
GPR35	“up-regulates activity”	GNA13	binding
5-(2-propoxyphenyl)-2,3-dihydrotriazolo[4,5-d]pyrimidin-7-one	“up-regulates activity”	GPR35	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	13
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1418 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240605568:GGG:G	donor_gain	1.0000
2:240605569:GGG:G	donor_gain	1.0000
2:240605571:G:GG	donor_gain	1.0000
2:240605569:GG:G	donor_gain	0.9900
2:240605570:GG:G	donor_gain	0.9900
2:240605572:T:A	donor_loss	0.9900
2:240618886:A:G	acceptor_gain	0.9900
2:240629938:T:TA	acceptor_gain	0.9900
2:240629941:T:TA	acceptor_gain	0.9900
2:240629946:CA:C	acceptor_loss	0.9900
2:240629947:A:AG	acceptor_gain	0.9900
2:240629948:G:GG	acceptor_gain	0.9900
2:240629948:GGA:G	acceptor_gain	0.9900
2:240629948:GGACC:G	acceptor_gain	0.9900
2:240618826:A:G	acceptor_gain	0.9800
2:240627175:C:G	donor_gain	0.9800
2:240627221:G:GG	donor_gain	0.9800
2:240629947:AG:A	acceptor_gain	0.9800
2:240629948:GG:G	acceptor_gain	0.9800
2:240605567:TGGG:T	donor_gain	0.9700
2:240605568:GGGG:G	donor_gain	0.9700
2:240616384:CTAG:C	acceptor_loss	0.9700
2:240616385:TAGGT:T	acceptor_loss	0.9700
2:240616386:A:AC	acceptor_loss	0.9700
2:240616387:G:GA	acceptor_loss	0.9700
2:240629936:T:TA	acceptor_gain	0.9700
2:240629948:GGAC:G	acceptor_gain	0.9700
2:240618825:A:AG	acceptor_gain	0.9600
2:240605566:CTGGG:C	donor_gain	0.9500
2:240612780:G:GT	donor_gain	0.9500

AlphaMissense

1968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240630640:T:C	F230L	0.996
2:240630642:C:A	F230L	0.996
2:240630642:C:G	F230L	0.996
2:240630490:T:C	F180L	0.994
2:240630492:C:A	F180L	0.994
2:240630492:C:G	F180L	0.994
2:240630135:C:A	N61K	0.990
2:240630135:C:G	N61K	0.990
2:240630150:C:A	D66E	0.990
2:240630150:C:G	D66E	0.990
2:240630259:A:C	S103R	0.989
2:240630261:C:A	S103R	0.989
2:240630261:C:G	S103R	0.989
2:240630628:T:C	F226L	0.989
2:240630630:C:A	F226L	0.989
2:240630630:C:G	F226L	0.989
2:240630768:C:A	D272E	0.988
2:240630768:C:G	D272E	0.988
2:240630265:A:C	S105R	0.987
2:240630267:C:A	S105R	0.987
2:240630267:C:G	S105R	0.987
2:240630647:C:G	P232R	0.987
2:240630052:G:C	G34R	0.985
2:240630647:C:A	P232H	0.985
2:240630756:C:A	N268K	0.985
2:240630756:C:G	N268K	0.985
2:240630149:A:C	D66A	0.984
2:240630373:T:A	W141R	0.984
2:240630373:T:C	W141R	0.984
2:240630149:A:T	D66V	0.983

dbSNP variants (sampled 300 via entrez): RS1000001290 (2:240615618 G>A), RS1000081291 (2:240633551 G>A), RS1000238975 (2:240628882 G>A,T), RS1000384083 (2:240605328 C>T), RS1000420757 (2:240613243 C>G), RS1000585791 (2:240616340 G>A), RS1000605282 (2:240614628 C>T), RS1000800408 (2:240623349 G>A,C), RS1000969778 (2:240604187 G>A), RS1001071223 (2:240621983 C>T), RS1001141441 (2:240632472 C>A,T), RS1001189034 (2:240627439 C>T), RS1001241517 (2:240627765 G>A,T), RS1001282858 (2:240625612 G>A), RS1001409991 (2:240620877 C>G)

Disease associations

OMIM: gene MIM:602646 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000083	Renal insufficiency
HP:0000554	Uveitis
HP:0000716	Depression
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000989	Pruritus
HP:0001081	Cholelithiasis
HP:0001298	Encephalopathy
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001541	Ascites
HP:0001635	Congestive heart failure
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001879	Abnormal eosinophil morphology
HP:0001945	Fever
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002240	Hepatomegaly
HP:0002608	Celiac disease
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002960	Autoimmunity
HP:0003073	Hypoalbuminemia
HP:0003459	Polyclonal elevation of IgM

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000964_31	Ulcerative colitis	8.000000e-11
GCST001615_2	Sclerosing cholangitis and ulcerative colitis (combined)	2.000000e-09
GCST001725_75	Inflammatory bowel disease	3.000000e-21
GCST003097_8	Pediatric autoimmune diseases	2.000000e-07
GCST004131_50	Inflammatory bowel disease	8.000000e-15
GCST004133_14	Ulcerative colitis	1.000000e-17
GCST004608_67	Granulocyte percentage of myeloid white cells	8.000000e-09
GCST004609_105	Monocyte percentage of white cells	8.000000e-10
GCST004625_61	Monocyte count	6.000000e-13
GCST005529_47	Ankylosing spondylitis	1.000000e-08
GCST005529_54	Ankylosing spondylitis	2.000000e-07
GCST005537_8	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-25
GCST005537_9	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	6.000000e-10
GCST008485_1	Crohn’s disease	6.000000e-11
GCST90002393_396	Monocyte count	1.000000e-34
GCST90002394_226	Monocyte percentage of white cells	7.000000e-33

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293267 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

30 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 528,725 (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
CHEMBL1096	AMLEXANOX	4	4,195
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4	5,428
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4	1,220
CHEMBL1201082	FLUOXETINE HYDROCHLORIDE	4	18,871
CHEMBL1201266	LODOXAMIDE	4	3,857
CHEMBL1324	TOLCAPONE	4	13,819
CHEMBL1466	DICUMAROL	4	12,198
CHEMBL1471	APREPITANT	4	901
CHEMBL1707	LOPERAMIDE HYDROCHLORIDE	4	59,532
CHEMBL2111101	PIMAVANSERIN	4	1,357
CHEMBL35	FUROSEMIDE	4	224,045
CHEMBL428880	CROMOLYN	4	14,789
CHEMBL493982	VORAPAXAR	4	1,021
CHEMBL50588	EMETINE	4	22,457
CHEMBL567	PERPHENAZINE	4	21,883
CHEMBL74	CROMOLYN SODIUM	4	28,575
CHEMBL953	ENTACAPONE	4	16,791
CHEMBL50	QUERCETIN	3	74,559
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL150764	BUFROLIN	2	131
CHEMBL151	LUTEOLIN	2
CHEMBL167055	NITECAPONE	2
CHEMBL232656	BX 471 FREE BASE	2
CHEMBL273386	2,4-DINITROPHENOL	2
CHEMBL28079	ZAPRINAST	2
CHEMBL405355	NIGULDIPINE	2
CHEMBL6246	ELLAGIC ACID	2
CHEMBL63323	NIFLUMIC ACID	2
CHEMBL8260	BAICALEIN	2
CHEMBL299155	TRANSTORINE	1

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12468485	GPR35		0.00	0

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 (9 total), top 9:

Ligand	Action	Affinity	Parameter
compound 83 [PMID: 23888932]	Agonist	9.23	pKi
lodoxamide	Agonist	9.0	pEC50
2-oleoyl-LPA	Agonist	7.52	pEC50
pamoic acid	Agonist	7.29	pEC50
zaprinast	Agonist	6.1	pEC50
furosemide	Agonist	5.63	pEC50
bumetanide	Agonist	5.54	pEC50
CID2745687	Antagonist	4.98	pIC50
kynurenic acid	Agonist	4.41	pEC50

Binding affinities (BindingDB)

114 measured of 234 human assays (265 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
7-[(E)-but-2-enyl]-3-methyl-8-(3-phenylpropylsulfanyl)purine-2,6-dione	EC50	0.00868 nM
(5Z)-3-[2-(1H-indol-3-yl)ethyl]-2-(4-methoxyphenyl)imino-5-[(5-morpholin-4-ylfuran-2-yl)methylidene]-1,3-thiazolidin-4-one	EC50	26.9 nM
SMR000198068	EC50	90.5 nM
cid_9581015	IC50	211 nM
MLS-0437442.0001	IC50	307 nM
methyl 5-[(E)-[(4-chlorophenyl)carbamothioylhydrazinylidene]methyl]-1-phenylpyrazole-4-carboxylate	IC50	319 nM
5-[(E)-[[anilino(sulfanylidene)methyl]hydrazinylidene]methyl]-1-(2,4-difluorophenyl)-4-pyrazolecarboxylic acid methyl ester	IC50	379 nM
MLS000563840	IC50	500 nM
(E)-1-[4-[4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]phenyl]-3-(dimethylamino)prop-2-en-1-one	IC50	530 nM
2-[(5-dec-9-enyl-1H-1,2,4-triazol-3-yl)sulfanyl]acetic acid	IC50	553 nM
4-[[4-oxo-2-[2-oxo-2-(4-propan-2-ylanilino)ethyl]sulfanylthieno[3,2-d]pyrimidin-3-yl]methyl]benzoic acid	IC50	561 nM
cid_24789825	IC50	626 nM
(5Z)-5-[[4-(dimethylamino)phenyl]methylidene]-3-(phenylmethyl)-2-sulfanylidene-imidazolidin-4-one	IC50	651 nM
MLS001212597	IC50	701 nM
SMR000523991	IC50	720 nM
6-nitro-3-(2-pyridinyl)-1H-indol-2-amine	IC50	787 nM
(5Z)-5-(dimethylaminomethylidene)-3-(4-propan-2-ylphenyl)-2-sulfanylidene-4-thiazolidinone	IC50	835 nM
MLS001151090	IC50	929 nM
3-methyl-7-pentyl-8-(2-phenylethylsulfanyl)purine-2,6-dione	IC50	935 nM
6-azanyl-2-methyl-8-thiophen-3-yl-1,3,8,8a-tetrahydroisoquinoline-5,7,7-tricarbonitrile	IC50	991 nM
MLS001205154	IC50	1000 nM
methyl 1-phenyl-5-[(E)-(phenylcarbamothioylhydrazinylidene)methyl]pyrazole-4-carboxylate	IC50	1010 nM
SMR000461567	IC50	1110 nM
N-(1,3-benzothiazol-2-yl)-3-nitro-4-piperidin-1-ylbenzamide	IC50	1120 nM
1-[(4-chlorophenyl)methyl]-4-[4-(2-methylphenyl)-1-piperazinyl]pyrazolo[3,4-d]pyrimidine	EC50	1140 nM
cid_6506792	IC50	1160 nM
4-[4-[(5E)-2,4-dioxo-5-[(E)-3-phenylprop-2-enylidene]-1,3-thiazolidin-3-yl]butanoylamino]benzoic acid	IC50	1170 nM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2,5-dimethyl-4-(4-methyl-1-piperidinyl)-6-thieno[2,3-d]pyrimidinecarboxamide	IC50	1200 nM
cid_814607	IC50	1220 nM
cid_9581013	IC50	1250 nM
MLS000948015	IC50	1260 nM
SMR000526932	IC50	1330 nM
methyl 1-[2,4-bis(fluoranyl)phenyl]-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]pyrazole-4-carboxylate	IC50	1390 nM
SMR000354546	IC50	1440 nM
SMR000639494	IC50	1460 nM
MLS000375336	EC50	1480 nM
2-hydroxy-4-({4-[5-(2-methyl-3-phenyl-2-propen-1-ylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]butanoyl}amino)benzoic acid	IC50	1560 nM
3-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)-6-(2-thienyl)-4-(trifluoromethyl)thieno[2,3-b]pyridine-2-carboxamide	IC50	1570 nM
cid_24761158	IC50	1620 nM
2-(4-pyridyl)-N-[4-(thiazol-2-ylsulfamoyl)phenyl]cinchoninamide	IC50	1640 nM
3-Bromo-4-chloro-7-diethylamino-chromen-2-one	IC50	1680 nM
methyl 1-[2,4-bis(fluoranyl)phenyl]-5-[(E)-[(4-chlorophenyl)carbamothioylhydrazinylidene]methyl]pyrazole-4-carboxylate	IC50	1690 nM
cid_1231538	EC50	1740 nM
cid_15945506	IC50	1780 nM
MLS001233767	IC50	1960 nM
N-[(4-ethoxyphenyl)methylideneamino]-2-[2-[3-(trifluoromethyl)anilino]-4-thiazolyl]acetamide	IC50	2100 nM
[4-(3-chlorophenyl)piperazin-1-yl]-(6-methoxyfuro[2,3-b]quinolin-2-yl)methanone	IC50	2140 nM
2-[4-[(E)-3-(4-cyclohexylphenyl)-3-oxidanylidene-prop-1-enyl]phenoxy]ethanoic acid	IC50	2160 nM
cid_720233	IC50	2160 nM
MLS-0004183.0001	IC50	2180 nM

ChEMBL bioactivities

764 potent at pChembl≥5 of 907 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.51	EC50	0.31	nM	CHEMBL4857772
9.33	IC50	0.47	nM	CHEMBL4857772
9.23	Ki	0.589	nM	CHEMBL2425821
9.15	EC50	0.71	nM	ZAPRINAST
9.13	IC50	0.74	nM	CHEMBL3306990
9.03	Ki	0.938	nM	CHEMBL2392171
8.97	EC50	1.08	nM	CHEMBL3306990
8.95	Ki	1.12	nM	CHEMBL2392179
8.86	Ki	1.37	nM	CHEMBL2425819
8.79	Ki	1.64	nM	CHEMBL2425820
8.72	Ki	1.92	nM	CHEMBL2425824
8.70	EC50	2	nM	PAMOIC ACID
8.70	IC50	2	nM	CHEMBL4870213
8.70	IC50	2	nM	CHEMBL3306990
8.68	EC50	2.1	nM	PAMOIC ACID
8.66	Ki	2.18	nM	CHEMBL2392172
8.61	IC50	2.45	nM	CHEMBL4856506
8.52	IC50	3	nM	CHEMBL4859764
8.52	EC50	3	nM	CHEMBL4100677
8.52	EC50	3	nM	PAMOIC ACID
8.49	EC50	3.2	nM	CHEMBL2392141
8.45	IC50	3.52	nM	CHEMBL4876009
8.41	Kd	3.9	nM	CHEMBL5281778
8.40	Ki	4	nM	CHEMBL1384502
8.38	Ki	4.12	nM	CHEMBL2392160
8.36	EC50	4.37	nM	CHEMBL2425820
8.35	EC50	4.45	nM	CHEMBL2425819
8.32	Ki	4.79	nM	CHEMBL2392170
8.29	Ki	5.18	nM	CHEMBL2392174
8.29	EC50	5.08	nM	CHEMBL4876009
8.28	Kd	5.27	nM	CHEMBL2425818
8.26	EC50	5.54	nM	CHEMBL2425821
8.26	Ki	5.5	nM	CHEMBL2392167
8.25	Kd	5.65	nM	CHEMBL2425818
8.25	IC50	5.6	nM	CHEMBL5285029
8.24	EC50	5.8	nM	CHEMBL4100677
8.24	EC50	5.781	nM	CHEMBL4100677
8.23	Kd	5.92	nM	CHEMBL2425818
8.22	EC50	6.06	nM	CHEMBL2425824
8.22	EC50	6	nM	CHEMBL3347474
8.22	IC50	6	nM	CHEMBL4861414
8.22	IC50	6	nM	CHEMBL4869539
8.22	Ki	6	nM	CHEMBL3306990
8.21	IC50	6.11	nM	CHEMBL4852667
8.16	EC50	6.93	nM	CHEMBL4856506
8.15	IC50	7	nM	CHEMBL4856506
8.13	Kd	7.4	nM	CHEMBL5289040
8.11	IC50	7.8	nM	CHEMBL5288015
8.10	EC50	8	nM	CHEMBL3306990
8.10	IC50	8	nM	CHEMBL4848109

PubChem BioAssay actives

594 with measured affinity, of 1243 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
4,17-dioxo-3,18-dioxatetracyclo[12.4.0.02,7.08,13]octadeca-1(14),2(7),5,8,10,12,15-heptaene-5,16-dicarboxylic acid	1775484: Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as dynamic mass redistribution response by DMR assay	ec50	0.0003	uM
6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0006	uM
5-(2-propoxyphenyl)-2,6-dihydrotriazolo[4,5-d]pyrimidin-7-one	1955635: Agonist activity at GPR-35 in human HT-29 cells by DMR assay	ec50	0.0007	uM
10-methyl-4,6-dioxo-1,9-dihydropyrido[3,2-g]quinoline-2,8-dicarboxylic acid	1775485: Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0007	uM
6-bromo-8-[(2,4-dichlorobenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0009	uM
6-bromo-8-[(2-chloro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0011	uM
6-bromo-8-[(2-fluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0014	uM
6-bromo-8-[(3-fluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0016	uM
6-chloro-8-[(2-fluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0019	uM
10-(4-methoxyphenyl)-2,8-dioxopyrano[3,2-g]chromene-3,7-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0020	uM
4-[(3-carboxy-2-hydroxynaphthalen-1-yl)methyl]-3-hydroxynaphthalene-2-carboxylic acid	1460079: Agonist activity at human GPR35 expressed in CHO-K1 cells by DMR assay	ec50	0.0020	uM
6-bromo-8-[(3,4-dichlorobenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0022	uM
6-(4-methoxyphenyl)-2,8-dioxopyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775485: Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0024	uM
6-bromo-7-hydroxy-8-nitro-3-(2H-tetrazol-5-yl)chromen-2-one	1955642: Agonist activity at GPR-35 in human HT-29 cells incubated for 1 hr by DMR assay	ec50	0.0030	uM
6-(3-methoxyphenyl)-2,8-dioxopyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0030	uM
4-[(Z)-[2-(2-fluorophenyl)imino-4-oxo-1,3-thiazolidin-5-ylidene]methyl]benzoic acid	769740: Agonist activity at human GPR35 by Ca+2 release assay	ec50	0.0032	uM
4,6-dichloro-10-methylpyrido[3,2-g]quinoline-2,8-dicarboxylic acid	1775485: Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0035	uM
4-[4-[1-[2-[4-(2,2-difluoro-5,10,12-trimethyl-1,6-diaza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-8-yl)phenoxy]ethyl]triazol-4-yl]butoxy]-10-methyl-6-oxo-9H-pyrido[3,2-g]quinoline-2,8-dicarboxylic acid	1955639: Binding affinity to Nluc-fused human GPR35 expressed in CHO-K1 cells using furimazine as substrate incubated for 30 mins in presence of zaprinast followed by substrate addition by BERT-based equilibrium binding assay	kd	0.0039	uM
2-hydroxy-4-[4-[(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoylamino]benzoic acid	1955641: Competitive binding affinity to Nluc-fused human GPR35 expressed in CHO-K1 cells assessed as inhibition constant using furimazine as substrate incubated for 30 mins followed by substrate addition by in presence of 10-(4-(2-(4-(4-((2,8-dicarboxy-6-hydroxy-10-methylpyrido[3,2-g]quinolin-4-yl)oxy)butyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-5,5-difluoro-2,7,9-trimethyl-5H-imidazo[1,2-c]pyrrolo[2,1-f][1,3,2]diazaborinin-6-ium-5-uide	ki	0.0040	uM
2-[2-chloro-5-cyano-3-(oxaloamino)anilino]-2-oxoacetic acid	1978210: Agonist activity at human GPR35 by beta-arrestin recruitment assay	ec50	0.0040	uM
8-[(2,4-dichlorobenzoyl)amino]-6-fluoro-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0041	uM
6-bromo-8-[(4-chlorobenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0048	uM
6-bromo-8-[(4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0052	uM
6-bromo-4-oxo-8-[[4-(tritritiomethoxy)benzoyl]amino]chromene-2-carboxylic acid	769733: Binding affinity to human recombinant GPR35 expressed in CHO cells after 150 mins by liquid scintillation counting analysis	kd	0.0053	uM
6-chloro-8-[(4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0055	uM
4-[5-[1-[2-[4-(2,2-difluoro-5,10,12-trimethyl-1,6-diaza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-8-yl)phenoxy]ethyl]triazol-4-yl]pentoxy]-10-methyl-6-oxo-9H-pyrido[3,2-g]quinoline-2,8-dicarboxylic acid	1955636: Agonist activity at GPR-35 in human HT-29 cells assessed as desensitization of zaprinast induced DMR response incubated for 1 hr followed by zaprinast stimulation	ic50	0.0056	uM
6-(3-fluorophenyl)-2,8-dioxopyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0060	uM
6-(2-fluorophenyl)-2,8-dioxopyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0060	uM
4,6-dimethoxy-10-methylpyrido[3,2-g]quinoline-2,8-dicarboxylic acid	1775485: Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0061	uM
4-[3-[1-[2-[4-(2,2-difluoro-5,10,12-trimethyl-1,6-diaza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-8-yl)phenoxy]ethyl]triazol-4-yl]propoxy]-10-methyl-6-oxo-9H-pyrido[3,2-g]quinoline-2,8-dicarboxylic acid	1955639: Binding affinity to Nluc-fused human GPR35 expressed in CHO-K1 cells using furimazine as substrate incubated for 30 mins in presence of zaprinast followed by substrate addition by BERT-based equilibrium binding assay	kd	0.0074	uM
4-[2-[2-[1-[2-[4-(2,2-difluoro-5,10,12-trimethyl-1,6-diaza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-8-yl)phenoxy]ethyl]triazol-4-yl]ethoxy]ethoxy]-10-methyl-6-oxo-9H-pyrido[3,2-g]quinoline-2,8-dicarboxylic acid	1955636: Agonist activity at GPR-35 in human HT-29 cells assessed as desensitization of zaprinast induced DMR response incubated for 1 hr followed by zaprinast stimulation	ic50	0.0078	uM
2,8-dioxo-6-(4-propan-2-ylphenyl)pyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0080	uM
10-bromo-2,8-dioxopyrano[3,2-g]chromene-3,7-dicarboxylic acid	1775485: Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0093	uM
N-[5-bromo-2-(2H-tetrazol-5-yl)phenyl]-4-methoxybenzamide	1955641: Competitive binding affinity to Nluc-fused human GPR35 expressed in CHO-K1 cells assessed as inhibition constant using furimazine as substrate incubated for 30 mins followed by substrate addition by in presence of 10-(4-(2-(4-(4-((2,8-dicarboxy-6-hydroxy-10-methylpyrido[3,2-g]quinolin-4-yl)oxy)butyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-5,5-difluoro-2,7,9-trimethyl-5H-imidazo[1,2-c]pyrrolo[2,1-f][1,3,2]diazaborinin-6-ium-5-uide	ki	0.0100	uM
8-[(3,4-dichlorobenzoyl)amino]-6-fluoro-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0115	uM
4,10-dioxo-1,7-dihydro-1,7-phenanthroline-2,8-dicarboxylic acid	1460080: Agonist activity at human GPR35 expressed in CHO-K1 cells after 90 mins by beta-arrestin 2 recruitment assay	ec50	0.0130	uM
7-hydroxy-6,8-dinitro-3-(2H-tetrazol-5-yl)chromen-2-one	1460082: Agonist activity at GPR35 in human HT-29 cells assessed as induction of cell desensitization to 1 uM zaprinast preincubated for 1 hr followed by zaprinast stimulation measured after 8 minutes by DMR assay	ic50	0.0130	uM
6-butyl-4,10-dioxo-1,7-dihydro-1,7-phenanthroline-2,8-dicarboxylic acid	1775491: Agonist activity at human GPR35 receptor expressed in HEK293T cells co-expressing beta-arrestin2 assessed as induction of beta-arrestin2 recruitment by BRET assay	ec50	0.0130	uM
N-[5-bromo-2-(2H-tetrazol-5-yl)phenyl]-2-fluoro-4-methoxybenzamide	1354829: Desensitization of GPR35 in human HT-29 cells assessed as inhibition of zaprinast-induced dynamic mass redistribution pretreated for 1 hr followed by zaprinast stimulation	ic50	0.0140	uM
2,8-dioxo-6-thiophen-2-ylpyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0150	uM
8-(1,3-benzodioxole-5-carbonylamino)-6-bromo-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0150	uM
6-bromo-2,8-dioxo-3-(2H-tetrazol-5-yl)pyrano[2,3-f]chromene-9-carboxylic acid	1775485: Agonist activity at human GPR35 receptor expressed in CHO-K1 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0159	uM
2,8-dioxo-6-phenylpyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0160	uM
5,6-dibromo-3-hydroxythieno[3,2-b]thiophene-2-carboxylic acid	665256: Agonist activity at GPR35 in human HT-29 cells by dynamic mass redistribution assay	ec50	0.0160	uM
3,7,11-trithiatricyclo[6.3.0.02,6]undeca-1(8),2(6),4,9-tetraene-4,10-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0200	uM
6-methoxy-8-[(4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0205	uM
6-(2-methoxyphenyl)-2,8-dioxopyrano[2,3-f]chromene-3,9-dicarboxylic acid	1775482: Agonist activity at human GPR35 receptor expressed in HT-29 cells assessed as desensitization of zaprinast-induced DMR response preincubated for 1 hr followed by zaprinast stimulation by DMR desensitization assay	ic50	0.0220	uM
6,8-dibromo-7-hydroxy-3-(2H-tetrazol-5-yl)chromen-2-one	1460082: Agonist activity at GPR35 in human HT-29 cells assessed as induction of cell desensitization to 1 uM zaprinast preincubated for 1 hr followed by zaprinast stimulation measured after 8 minutes by DMR assay	ic50	0.0230	uM
6-fluoro-8-[(4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid	769725: Displacement of [3H]PSB-13253 from human recombinant GPR35 exprssed in CHO cells by liquid scintillation counting analysis	ki	0.0254	uM
2-methylpropyl 4-chloro-3,5-bis[(2-ethoxy-2-oxoacetyl)amino]benzoate	1978185: Agonist activity at human GPR35 expressed in HEK293 cells co-expressing Galpha16 assessed as increase in calcium mobilization by Fluo-4 AM dye based fluorescence assay	ec50	0.0255	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
zaprinast	increases activity, affects localization, decreases reaction, affects binding	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
pamoic acid	affects localization, decreases reaction, affects binding, increases activity, increases reaction	3
oxantel pamoate	affects binding, increases activity	2
Cromolyn Sodium	decreases reaction, affects binding, increases activity, affects localization	2
Quercetin	increases activity, increases expression, affects binding	2
aristolochic acid I	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
3-hydroxy-2-naphthoic acid	affects binding, increases activity	1
1,4-dihydroxy-2-naphthoic acid	affects binding, increases activity	1
pyrvinium	affects binding, increases activity	1
aflatoxin B2	increases methylation	1
5-nitro-2-(3-phenylpropylamino)benzoic acid	affects binding, increases activity	1
2-(3-cyano-5-(3,4-dichlorophenyl)-4,5-dimethylfuran-2(5H)-ylidene)malononitrile	affects binding, increases activity	1
6-bromo-3-methylthieno(3,2-b)thiophene-2-carboxylic acid	affects binding, increases activity	1
methyl 5-((tert-butylcarbamothioylhydrazinylidene)methyl)-1-(2,4-difluorophenyl)pyrazole-4-carboxylate	affects localization, decreases reaction, affects binding, increases activity	1
2-hydroxy-4-(4-(5-(2-methyl-3-phenylprop-2-enylidene)-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl)butanoylamino)benzoic acid	decreases reaction, affects binding, increases activity, affects localization	1
Allergens	increases expression	1
Dicumarol	affects binding, increases activity	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Fluorouracil	increases expression, affects response to substance	1
Kynurenic Acid	affects binding, increases activity	1
Niflumic Acid	affects binding, increases activity	1
Pyrantel Pamoate	increases activity, affects binding	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Vanadium	increases abundance, increases methylation	1
Cyclosporine	decreases methylation	1
Paclitaxel	decreases response to substance	1

ChEMBL screening assays

162 unique, capped per target: 84 binding, 78 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613835	Functional	PUBCHEM_BIOASSAY: Image-Based HTS for Selective Antagonists of GPR35. High content imaging assay of the inhibition of receptor-mediated beta-arrestin GFP translocation to cytosolic compartments Secondary Screen (Class of assay: confirmatory	PubChem BioAssay data set
CHEMBL2039375	Binding	Desensitization of GPR35 receptor in human HT-29 cells assessed as inhibition of zaprinast-induced dynamic mass redistribution after 10 mins	Discovery of Natural Phenols as G Protein-Coupled Receptor-35 (GPR35) Agonists. — ACS Med Chem Lett

Cellosaurus cell lines

4 cell lines: 2 spontaneously immortalized cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV29	cAMP Hunter CHO-K1 GPR35 Gi	Spontaneously immortalized cell line	Female
CVCL_KX59	PathHunter CHO-K1 GPR35 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA43	PathHunter U2OS GPR35 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZL10	Tango GPR35-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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