CMKLR1

Summary

CMKLR1 (chemerin chemokine-like receptor 1, HGNC:2121) is a protein-coding gene on chromosome 12q23.3, encoding Chemerin-like receptor 1 (Q99788). Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1.

Enables adipokinetic hormone binding activity and adipokinetic hormone receptor activity. Involved in several processes, including negative regulation of NF-kappaB transcription factor activity; positive regulation of macrophage chemotaxis; and regulation of calcium-mediated signaling. Located in plasma membrane.

Source: NCBI Gene 1240 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 62 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001142343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2121
Approved symbol	CMKLR1
Name	chemerin chemokine-like receptor 1
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	RVER1, ERV1, ChemR23
Ensembl gene	ENSG00000174600
Ensembl biotype	protein_coding
OMIM	602351
Entrez	1240

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000312143, ENST00000412676, ENST00000549466, ENST00000550402, ENST00000550573, ENST00000552995, ENST00000881053, ENST00000881054, ENST00000881055, ENST00000916364, ENST00000971700, ENST00000971701, ENST00000971702, ENST00000971703, ENST00000971704

RefSeq mRNA: 4 — MANE Select: NM_001142343 NM_001142343, NM_001142344, NM_001142345, NM_004072

CCDS: CCDS41829, CCDS44965

Canonical transcript exons

ENST00000550402 — 4 exons

Exon	Start	End
ENSE00002324937	108329995	108330207
ENSE00002355908	108339027	108339311
ENSE00002427280	108288046	108292959
ENSE00003462153	108293589	108293664

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 90.65.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8469 / max 344.5200, expressed in 641 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133111	4.5785	623
133106	0.2349	86
133110	0.0336	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	90.65	gold quality
descending thoracic aorta	UBERON:0002345	89.58	gold quality
calcaneal tendon	UBERON:0003701	88.99	gold quality
tendon of biceps brachii	UBERON:0008188	88.84	gold quality
tendon	UBERON:0000043	87.67	gold quality
thoracic aorta	UBERON:0001515	87.19	gold quality
ascending aorta	UBERON:0001496	87.16	gold quality
granulocyte	CL:0000094	86.64	gold quality
spleen	UBERON:0002106	85.93	gold quality
coronary artery	UBERON:0001621	84.98	gold quality
left coronary artery	UBERON:0001626	84.88	gold quality
aorta	UBERON:0000947	84.53	gold quality
monocyte	CL:0000576	83.22	gold quality
leukocyte	CL:0000738	83.02	gold quality
tibial artery	UBERON:0007610	82.68	gold quality
popliteal artery	UBERON:0002250	82.66	gold quality
mononuclear cell	CL:0000842	82.65	gold quality
layer of synovial tissue	UBERON:0007616	81.97	gold quality
smooth muscle tissue	UBERON:0001135	81.96	gold quality
lymph node	UBERON:0000029	81.84	gold quality
saphenous vein	UBERON:0007318	80.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.74	gold quality
rectum	UBERON:0001052	78.47	gold quality
upper lobe of left lung	UBERON:0008952	78.33	gold quality
synovial joint	UBERON:0002217	77.67	gold quality
secondary oocyte	CL:0000655	77.54	silver quality
upper lobe of lung	UBERON:0008948	77.35	gold quality
right lung	UBERON:0002167	77.26	gold quality
apex of heart	UBERON:0002098	77.17	gold quality
omental fat pad	UBERON:0010414	76.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF15, PPARA

miRNA regulators (miRDB)

149 targeting CMKLR1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Literature-anchored findings (GeneRIF, showing 40)

• ChemR23 mediates the Resolvin E1 signal to attenuate nuclear factor-kappaB (PMID:15753205)
• The results strongly support that the chemerin receptor, in the presence of CD4, functions as a “minor co-receptor” promoting infection by HIV-1, HIV-2 and SIV. (PMID:16904155)
• CMKLR1 is expressed by circulating pDC in normal individuals and patients suffering from skin diseases, such as psoriasis and atopic dermatitis. (PMID:19168032)
• RvE1 initiates direct activation of ChemR23 and signals receptor-dependent phosphorylation (PMID:19906641)
• the presence of ChemR23 in human endothelial cells, its significant up-regulation by pro-inflammatory cytokines, and its role in angiogenesis were demonstrated. (PMID:20044979)
• These results demonstrate that human chondrocytes express both the receptor ChemR23 and the ligand chemerin…which may play pivotal roles in joint inflammation. (PMID:21192818)
• The ChemR23/Chemerin axis may have a role in the recruitment of dendritic cells within the kidney in patients affected by lupus nephritis. (PMID:21346723)
• A genetic variation in the chemokine-like receptor 1 (CMKLR1) gene was statistically significantly associated with decreased overall survival in the three individual populations as well as in pooled analyses. (PMID:21483023)
• Chemerin, a ligand for the G-protein coupled receptor chemokine-like receptor 1, requires carboxy-terminal proteolytic processing to unleash its chemoattractant activity (PMID:21715684)
• The interaction of chemerin and ChemR23 may play an important role in the pathogenesis of rheumatoid arthritis through the resultant activation of fibroblast-like synoviocytes. (PMID:21959042)
• review of current research on biological roles of chemerin and chemokine-like receptor 1; highlight roles in mediating obesity and development of type 2 diabetes [REVIEW] (PMID:22610747)
• These results rule out the direct anti-inflammatory effect of chemerin on macrophages ex vivo, described previously in the literature, despite the expression of a functional ChemR23 receptor in these cells. (PMID:22768214)
• ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. (PMID:23469143)
• Prochemerin processing protease converts prochemerin into active chemerinF; the activating truncation by the protease may trigger a structural C-terminal rearrangement leading to increased affinity of chemerin to chemokine-like receptor (CMKLR)1. (PMID:23495698)
• Chemerin receptor showed increased expression in the lymph nodes and the spleen. (PMID:23904282)
• ChemR23 is expressed in neutrophil granules and rapidly upregulated upon neutrophil activation. (PMID:23999103)
• Development of a membrane-anchored chemerin receptor agonist as a novel modulator of allergic airway inflammation and neuropathic pain. (PMID:24659779)
• This study identified the up-regulation of ChemR23 in post-traumatic injury of calcaneal articular fracture (PMID:24689495)
• Results lend some support to a presumable role of locally produced chemerin in the progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor. (PMID:24779513)
• The effects of diclofenac on the incidence of pancreatitis following endoscopic retrograde cholangiopancreatography via lipoxin A4 and resolvin D1 and E1 levels is reported. (PMID:25030943)
• Results indicate that Abeta42 activates CMKLR1, leading to glia cell migration and clearance of Abeta42; and is involved in Abeta processing and clearance (PMID:25079809)
• The study for the first time confirmed a marked expression of chemerin and CMKLR1 in the liver of chronic hepatitis patients. (PMID:25121101)
• Increased chemerin expression in dermal blood vessels may be associated with the development of digital ulcers in systemic sclerosis. (PMID:25539827)
• Gestational obesity and gestational diabetes mellitus may contribute to elevated serum chemerin. Serum chemerin in pregnancy was associated with insulin resistance and triglycerides. Chemerin gene may play a role both in obese and gestational diabetes mellitus patients (PMID:25627894)
• ChemR23, the receptor for chemerin and resolvin E1, is expressed and functional on M1 but not on M2 macrophages. (PMID:25637017)
• Our results show that higher levels of circulating chemerin, CRP, fibrinogen, and ESR are associated with an increased risk of developing colorectal cancer (PMID:26628300)
• Results show that ChemR23 is highly expressed in squamous oesophageal cancer tumors and cell lines. (PMID:27092781)
• Data show inverse Relationship of the CMKLR1 Relative Expression and Chemerin Serum Levels in Obesity with Dysmetabolic Phenotype and Insulin Resistance (PMID:27239101)
• Study shows that hepatic CMKLR1 mRNA is weakly associated with features of NASH in male patients only. (PMID:27548138)
• CMKLR1 and GPR1 were widely expressed in vascular smooth muscle. (PMID:27742615)
• CMKLR1 exacerbated the proliferation and migration of VSMCs by activating ERK1/2. (PMID:27792688)
• Both ALX and ChemR23 were present in human synovium and medial tibial plateau bone obtained following total knee replacement surgery for osteoarthritis. (PMID:27860453)
• We demonstrated that chemerin is linked to metabolic syndrome components. Moreover, serum chemerin levels were associated significantly with obesity, especially visceral adipose tissue, in subjects with T2DM [type 2 diabetes mellitus]. (PMID:28120562)
• This study identified an ERV1/ChemR23 variant that protects patients with obesity from excessive inflammatory burden. (PMID:29146976)
• levels in cord blood, peripheral blood, adipose tissue and placenta tissue significantly higher in gestational diabetes (PMID:29430984)
• The expression level of chemerin in women who had experienced early spontaneous abortion was lower than in those who had experienced normal early pregnancy; conversely, CMKLR1 expression was higher in the former than in the latter. (PMID:29556954)
• Chemerin upregulated expression and phosphatase activity of PTEN by interfering with PTEN-CMKLR1 interaction, leading to weakened ubiquitination of PTEN and decreased p-Akt (Ser473) level, which was responsible for suppressed migration, invasion and metastasis of HCC cells. (PMID:29717200)
• Report a modest inverse association between chemerin and ankle-brachial index that remained consistent after adjustment for metabolic and inflammatory parameters in subclinical atherosclerosis. (PMID:29853566)
• Chemerin levels were lower in subfertile men compared to controls. Men with elevated LH levels had lower chemerin levels compared to those with LH levels within the normal range. (PMID:30304526)
• chemerin/ChemR23 axis played an important role in endothelial injury and inflammation in diabetic nephropathy. (PMID:30784180)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cmklr1	ENSDARG00000090890
danio_rerio	cmklr1l1	ENSDARG00000109654
danio_rerio	cmklrl2	ENSDARG00000110362
mus_musculus	Cmklr1	ENSMUSG00000042190
rattus_norvegicus	Cmklr1	ENSRNOG00000000704

Paralogs (8): C5AR2 (ENSG00000134830), GPR32 (ENSG00000142511), FPR2 (ENSG00000171049), FPR1 (ENSG00000171051), C3AR1 (ENSG00000171860), FPR3 (ENSG00000187474), C5AR1 (ENSG00000197405), GPR33 (ENSG00000214943)

Protein

Protein identifiers

Chemerin-like receptor 1 — Q99788 (reviewed: Q99788)

Alternative names: Chemokine-like receptor 1, G-protein coupled receptor ChemR23, G-protein coupled receptor DEZ

All UniProt accessions (3): Q99788, F8VSC8, F8VYN7

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with RARRES2 initiates activation of G proteins G(i)/G(o) and beta-arrestin pathways inducing cellular responses via second messenger pathways such as intracellular calcium mobilization, phosphorylation of MAP kinases MAPK1/MAPK3 (ERK1/2), TYRO3, MAPK14/P38MAPK and PI3K leading to multifunctional effects, like reduction of immune responses, enhancing of adipogenesis and angionesis. Resolvin E1 down-regulates cytokine production in macrophages by reducing the activation of MAPK1/3 (ERK1/2) and NF-kappa-B. Positively regulates adipogenesis and adipocyte metabolism. (Microbial infection) Acts as a coreceptor for several SIV strains (SIVMAC316, SIVMAC239, SIVMACL7E-FR and SIVSM62A), as well as a primary HIV-1 strain (92UG024-2).

Subcellular location. Cell membrane.

Tissue specificity. Prominently expressed in developing osseous and cartilaginous tissue. Also found in adult parathyroid glands. Expressed in cardiovascular system, brain, kidney, gastrointestinal tissues and myeloid tissues. Expressed in a broad array of tissues associated with hematopoietic and immune function including, spleen, thymus, appendix, lymph node, bone marrow and fetal liver. Among leukocyte populations abundant expression in monocyte-derived macrophage and immature dendritic cells (DCs). High expression in blood monocytes and low levels in polymorphonuclear cells and T-cells. Expressed on endothelial cells. Highly expressed in differentiating adipocytes.

Induction. Up-regulated by inflammatory cytokines TNF and IFN-gamma in monocytes. Up-regulated by TNF, IL-1-beta and IL-6 in endothelial cells.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the chemokine-like receptor (CMKLR) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99788-1	A	yes
Q99788-2	B

RefSeq proteins (4): NP_001135815, NP_001135816, NP_001135817, NP_004063 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000826	Formyl_rcpt-rel	Family
IPR002258	CML1	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (48 total): helix 11, topological domain 8, transmembrane region 7, modified residue 5, strand 5, turn 3, compositionally biased region 2, glycosylation site 2, chain 1, region of interest 1, disulfide bond 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7YKD	ELECTRON MICROSCOPY	2.81
8SG1	ELECTRON MICROSCOPY	2.94
8ZJG	ELECTRON MICROSCOPY	3.18
9L3W	ELECTRON MICROSCOPY	3.5
9L3Z	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99788-F1	78.84	0.50

Antibody-complex structures (SAbDab): 4 — 7YKD, 8SG1, 8ZJG, 9L3Z

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): 339, 342, 349, 352, 358

Disulfide bonds (1): 112–189

Glycosylation sites (2): 9, 192

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 282 (showing top): GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_TAXIS

GO Biological Process (18): skeletal system development (GO:0001501), complement receptor mediated signaling pathway (GO:0002430), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), positive regulation of macrophage chemotaxis (GO:0010759), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), negative regulation of interleukin-12 production (GO:0032695), positive regulation of fat cell differentiation (GO:0045600), regulation of calcium-mediated signaling (GO:0050848), positive regulation of cold-induced thermogenesis (GO:0120162), cell communication (GO:0007154), signal transduction (GO:0007165), signaling (GO:0023052), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (7): complement receptor activity (GO:0004875), G protein-coupled receptor activity (GO:0004930), chemokine receptor activity (GO:0004950), signaling receptor activity (GO:0038023), adipokinetic hormone receptor activity (GO:0097003), adipokinetic hormone binding (GO:0097004), protein binding (GO:0005515)

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	3
cellular process	2
transmembrane signaling receptor activity	2
system development	1
immune response-activating cell surface receptor signaling pathway	1
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
regulation of biological quality	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
negative regulation of cytokine production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
calcium-mediated signaling	1
regulation of intracellular signal transduction	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of biological process	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
complement binding	1
complement receptor mediated signaling pathway	1
immune receptor activity	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMKLR1	RARRES2	Q99969	999
CMKLR1	NAMPT	P43490	749
CMKLR1	HSH2D	Q96JZ2	745
CMKLR1	PTEN	P60484	697
CMKLR1	GFER	P55789	668
CMKLR1	ADIPOQ	Q15848	624
CMKLR1	CCL5	P13501	611
CMKLR1	CCL19	Q99731	604
CMKLR1	LTB4R	Q15722	604
CMKLR1	RETN	Q9HD89	594
CMKLR1	RETNLB	Q9BQ08	594
CMKLR1	CCRL2	O00421	593
CMKLR1	ADIPOR2	Q86V24	582
CMKLR1	ADIPOR1	Q96A54	575
CMKLR1	HLA-DQA2	P01906	572

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CMKLR1	SC5D	psi-mi:“MI:0914”(association)	0.530
RAMP1	CMKLR1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CMKLR1	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CMKLR1	psi-mi:“MI:0915”(physical association)	0.400
CMKLR1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CMKLR1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
CMKLR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
CMKLR1	BTAF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (98): ABCC4 (Affinity Capture-MS), OPA1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), EXOC3 (Affinity Capture-MS), JAK1 (Affinity Capture-MS), BTAF1 (Affinity Capture-MS), ATP9A (Affinity Capture-MS), TUBGCP2 (Affinity Capture-MS), HELLS (Affinity Capture-MS), DOLK (Affinity Capture-MS), DPY19L1 (Affinity Capture-MS), MTOR (Affinity Capture-MS), ATL2 (Affinity Capture-MS)

ESM2 similar proteins: A4FUQ5, B1PHQ8, B9VR26, O35786, O70129, O88536, O88537, O97571, P0C7U4, P0C7U5, P21109, P21730, P25024, P25025, P25089, P25090, P30992, P30993, P32248, P33766, P35344, P35407, P51686, P55919, P55920, P79175, P79177, P79188, P79189, P79190, P79191, P79234, P79235, P79236, P79237, P79240, P79242, P79243, P97468, P97520

Diamond homologs: A4FUQ5, B1PHQ8, B9VR26, O08565, O08790, O35210, O35786, O62747, O70129, O75388, O77590, O88416, O88536, O88537, O97571, O97664, P0C7U4, P0C7U5, P21462, P21730, P25025, P25089, P25090, P25095, P25104, P28646, P29089, P29754, P29755, P30555, P30556, P30872, P30873, P30937, P30992, P30993, P31391, P33766, P34976, P35373

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

728 predictions. Top by Δscore:

Variant	Effect	Δscore
12:108292955:ATTCT:A	acceptor_gain	1.0000
12:108292956:TTCT:T	acceptor_gain	1.0000
12:108292958:CT:C	acceptor_gain	1.0000
12:108292959:TCTGC:T	acceptor_loss	1.0000
12:108292960:C:CC	acceptor_gain	1.0000
12:108292961:T:A	acceptor_loss	1.0000
12:108293582:T:TA	donor_gain	1.0000
12:108339029:T:A	donor_gain	1.0000
12:108339030:C:A	donor_gain	1.0000
12:108339021:TGATA:T	donor_loss	0.9900
12:108339022:GATAC:G	donor_loss	0.9900
12:108339023:ATAC:A	donor_loss	0.9900
12:108339024:TA:T	donor_loss	0.9900
12:108339025:A:AT	donor_loss	0.9900
12:108339026:C:CA	donor_loss	0.9900
12:108339056:T:TA	donor_gain	0.9900
12:108292963:C:CT	acceptor_gain	0.9800
12:108292964:A:T	acceptor_gain	0.9800
12:108302243:C:A	donor_gain	0.9700
12:108292957:TCT:T	acceptor_gain	0.9600
12:108292958:CTC:C	acceptor_gain	0.9600
12:108292959:TCT:T	acceptor_gain	0.9600
12:108292960:C:A	acceptor_gain	0.9600
12:108315949:A:AC	donor_gain	0.9600
12:108315950:C:CC	donor_gain	0.9600
12:108339106:TGCAC:T	donor_gain	0.9600
12:108339238:A:AC	donor_gain	0.9600
12:108314379:T:TA	acceptor_gain	0.9200
12:108293584:CTCAC:C	donor_loss	0.9100
12:108293586:CACCA:C	donor_loss	0.9100

AlphaMissense

2498 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:108292648:C:A	W105C	0.997
12:108292648:C:G	W105C	0.997
12:108292561:G:C	S134R	0.996
12:108292561:G:T	S134R	0.996
12:108292563:T:G	S134R	0.996
12:108292156:G:C	F269L	0.995
12:108292156:G:T	F269L	0.995
12:108292158:A:G	F269L	0.995
12:108292628:C:G	C112S	0.995
12:108292629:A:T	C112S	0.995
12:108292450:A:C	S171R	0.994
12:108292450:A:T	S171R	0.994
12:108292452:T:G	S171R	0.994
12:108292650:A:G	W105R	0.994
12:108292650:A:T	W105R	0.994
12:108292276:G:C	F229L	0.993
12:108292276:G:T	F229L	0.993
12:108292278:A:G	F229L	0.993
12:108292397:C:G	C189S	0.993
12:108292398:A:T	C189S	0.993
12:108292819:G:C	S48R	0.993
12:108292819:G:T	S48R	0.993
12:108292821:T:G	S48R	0.993
12:108292430:C:G	R178P	0.992
12:108292803:C:G	G54R	0.992
12:108292803:C:T	G54R	0.992
12:108292149:A:G	C272R	0.991
12:108292396:G:C	C189W	0.991
12:108292036:G:C	S309R	0.990
12:108292036:G:T	S309R	0.990

dbSNP variants (sampled 300 via entrez): RS1000215717 (12:108339389 C>G,T), RS1000230017 (12:108310535 C>G), RS1000232274 (12:108322891 C>T), RS1000266238 (12:108340509 GAAGA>G), RS1000304925 (12:108334960 G>T), RS1000341728 (12:108298778 C>A), RS1000383079 (12:108290636 T>C), RS1000418664 (12:108307915 G>A,C), RS1000495860 (12:108331123 G>A), RS1000638953 (12:108314989 G>A), RS1000640399 (12:108326975 T>C), RS1000840417 (12:108312764 C>T), RS1000995845 (12:108288539 C>T), RS1001025492 (12:108288263 G>A), RS1001050123 (12:108318070 A>G)

Disease associations

OMIM: gene MIM:602351 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000824_1	Erectile dysfunction and prostate cancer treatment	8.000000e-07
GCST001035_1	Response to platinum-based chemotherapy in non-small-cell lung cancer	5.000000e-07
GCST001569_2	Bipolar disorder	9.000000e-07
GCST002408_11	Response to methotrexate in juvenile idiopathic arthritis	4.000000e-06
GCST002481_2	Acne (severe)	5.000000e-06
GCST004608_181	Granulocyte percentage of myeloid white cells	6.000000e-12
GCST004609_196	Monocyte percentage of white cells	6.000000e-16
GCST004625_125	Monocyte count	2.000000e-17
GCST007323_14	Risk-taking tendency (4-domain principal component model)	7.000000e-09
GCST010197_3	Protein level change in low calorie diet obesity intervention	2.000000e-06
GCST90002393_425	Monocyte count	5.000000e-36
GCST90002394_376	Monocyte percentage of white cells	1.000000e-40

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0008579	risk-taking behaviour
EFO:0004747	protein measurement
EFO:0010731	response to low calorie diet

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3540 (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: 407 (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
CHEMBL1742483	RESOLVIN E1	1	407

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Chemerin receptors

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
tethered chemerin 9	Agonist	8.26	pIC50
chemerin C-terminal peptide	Full agonist	8.15	pKd
chemerin	Full agonist	8.01	pEC50
[3H]resolvin E1	Agonist	7.95	pKd
resolvin E1	Full agonist	7.95	pKd
compound 14f [PMID: 35063894]	Antagonist	7.92	pIC50
S-26d [PMID: 37883692]	Antagonist	7.44	pIC50
α-NETA	Antagonist	6.43	pIC50
LC52-0332	Antagonist	5.24	pIC50

ChEMBL bioactivities

252 potent at pChembl≥5 of 253 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.60	EC50	0.2512	nM	CHEMBL6188463
9.52	EC50	0.3	nM	CHEMBL6188463
9.10	EC50	0.8	nM	CHEMBL6189452
9.10	EC50	0.8	nM	CHEMBL6190065
9.10	EC50	0.7943	nM	CHEMBL6189452
9.10	EC50	0.7943	nM	CHEMBL6190065
9.00	EC50	1	nM	RESOLVIN E1
9.00	EC50	1	nM	CHEMBL6190960
8.96	EC50	1.1	nM	CHEMBL6192232
8.96	EC50	1.1	nM	CHEMBL6190960
8.92	IC50	1.2	nM	CHEMBL4746987
8.90	EC50	1.259	nM	CHEMBL6190143
8.90	EC50	1.259	nM	CHEMBL6189386
8.90	EC50	1.259	nM	CHEMBL6192232
8.90	EC50	1.259	nM	CHEMBL6190898
8.90	EC50	1.259	nM	CHEMBL6191474
8.90	EC50	1.259	nM	CHEMBL6191903
8.90	EC50	1.259	nM	CHEMBL6191202
8.89	IC50	1.3	nM	CHEMBL4757632
8.89	EC50	1.3	nM	CHEMBL6190143
8.85	EC50	1.4	nM	CHEMBL6189386
8.85	EC50	1.4	nM	CHEMBL6190898
8.85	EC50	1.4	nM	CHEMBL6191474
8.85	EC50	1.4	nM	CHEMBL6191903
8.85	EC50	1.4	nM	CHEMBL6191202
8.82	EC50	1.5	nM	CHEMBL6192637
8.80	EC50	1.6	nM	CHEMBL6189350
8.80	EC50	1.585	nM	CHEMBL6189350
8.80	EC50	1.585	nM	CHEMBL6190365
8.80	EC50	1.585	nM	CHEMBL6192637
8.80	EC50	1.585	nM	CHEMBL6189224
8.77	EC50	1.7	nM	CHEMBL6190365
8.74	EC50	1.8	nM	CHEMBL6189224
8.74	EC50	1.8	nM	CHEMBL6188309
8.70	EC50	2	nM	CHEMBL6193503
8.70	EC50	2	nM	CHEMBL6188518
8.70	EC50	2	nM	CHEMBL6193686
8.70	EC50	1.995	nM	CHEMBL6193503
8.70	EC50	1.995	nM	CHEMBL6188518
8.70	EC50	1.995	nM	CHEMBL6188309
8.70	EC50	1.995	nM	CHEMBL6193686
8.70	EC50	1.995	nM	CHEMBL6190838
8.68	EC50	2.1	nM	CHEMBL6190838
8.64	IC50	2.3	nM	CHEMBL4793378
8.62	EC50	2.4	nM	CHEMBL6190219
8.60	EC50	2.5	nM	CHEMBL6190928
8.60	EC50	2.512	nM	CHEMBL6191030
8.60	EC50	2.512	nM	CHEMBL6191839
8.60	EC50	2.512	nM	CHEMBL6188611
8.60	EC50	2.512	nM	CHEMBL6190928

PubChem BioAssay actives

160 with measured affinity, of 264 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
(5S,6Z,8E,10E,12R,14Z,16E,18R)-5,12,18-trihydroxyicosa-6,8,10,14,16-pentaenoic acid	2020902: Antagonist activity at human CMKLR1	ec50	0.0010	uM
2-[butyl-[(1R)-1-[4-[5-chloro-2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazole-4-carboxylic acid	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0012	uM
2-[[(1R)-1-[4-[5-chloro-2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]ethyl]-(cyclopropylmethyl)amino]-1,3-benzoxazole-4-carboxylic acid	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0013	uM
2-[cyclopropylmethyl-[(1R)-1-[4-[5-fluoro-2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazole-4-carboxylic acid	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0023	uM
2-[butyl-[(1R)-1-[4-[5-fluoro-2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazole-4-carboxylic acid	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0027	uM
2-[cyclopropylmethyl-[(1R)-1-[4-[5-methyl-2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazole-4-carboxylic acid	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0032	uM
2-[[(1R)-1-[4-[5-chloro-2-(ethylcarbamoyl)phenyl]phenyl]ethyl]-(cyclopropylmethyl)amino]-5-cyclopropyl-N-cyclopropylsulfonyl-1,3-thiazole-4-carboxamide	1901253: Inhibition of human ChemR23 expressed in CAL-1 cells assessed as reduction in chemerin-induced calcium signaling	ic50	0.0048	uM
(4R,7S,10S,13S,16S,19R)-19-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-16-(3-amino-3-oxopropyl)-7,13-dibenzyl-10-methyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacyclohenicosane-4-carboxylic acid	1813945: Agonist activity at wild type CMKL1 (unknown origin) expressed in COS-7 cells assessed as increase in calcium flux measured for 40 sec by Fluo-2 AM dye based assay	ec50	0.0055	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoic acid	1813945: Agonist activity at wild type CMKL1 (unknown origin) expressed in COS-7 cells assessed as increase in calcium flux measured for 40 sec by Fluo-2 AM dye based assay	ec50	0.0090	uM
2-[[(1R)-1-[4-[5-chloro-2-[2-[2-[2-[2-[2-[2-[2-[13-[4-(ethylamino)-4-oxobutanoyl]-3,4,5,13-tetrazatetracyclo[13.4.0.02,6.07,12]nonadeca-1(19),2(6),3,7,9,11,15,17-octaen-5-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]phenyl]phenyl]ethyl]-(cyclopropylmethyl)amino]-5-cyclopropyl-N-cyclopropylsulfonyl-1,3-thiazole-4-carboxamide	1901253: Inhibition of human ChemR23 expressed in CAL-1 cells assessed as reduction in chemerin-induced calcium signaling	ic50	0.0091	uM
N-butyl-4-(1-methylimidazol-2-yl)-N-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0100	uM
2-[cyclopropylmethyl-[(1R)-1-[4-[2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazole-4-carboxylic acid	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0110	uM
2-[[(1R)-1-[4-[2-[2-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]-5-chlorophenyl]phenyl]ethyl]-(cyclopropylmethyl)amino]-5-cyclopropyl-N-cyclopropylsulfonyl-1,3-thiazole-4-carboxamide	1901253: Inhibition of human ChemR23 expressed in CAL-1 cells assessed as reduction in chemerin-induced calcium signaling	ic50	0.0120	uM
2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-N,N-dimethyl-1,3-benzoxazole-4-carboxamide	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0130	uM
N-[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-4-yl]methanesulfonamide	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0140	uM
2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-N-methylsulfonyl-1,3-benzoxazole-4-carboxamide	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0140	uM
2-[[(1R)-1-[4-[2-[2-[2-[2-[2-[2-[2-[2-[13-[3-[3-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]propanoyl]-3,4,5,13-tetrazatetracyclo[13.4.0.02,6.07,12]nonadeca-1(19),2(6),3,7,9,11,15,17-octaen-5-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]-5-chlorophenyl]phenyl]ethyl]-(cyclopropylmethyl)amino]-5-cyclopropyl-N-cyclopropylsulfonyl-1,3-thiazole-4-carboxamide	1901253: Inhibition of human ChemR23 expressed in CAL-1 cells assessed as reduction in chemerin-induced calcium signaling	ic50	0.0140	uM
2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazole-4-carboxylic acid	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0170	uM
(3S)-3-[4-[[1-cyclopentyl-3-(3,5-dichloro-4-hydroxyphenyl)-4-fluoroindazol-6-yl]methoxy]phenyl]butanoic acid	2020903: Antagonist activity at human CMKLR1 expressed in CHO-K1 cells co-expressing Galpha-16 assessed as change in intracellular calcium concentration incubated for 30 mins in presence of chemerin-9 by FLIPR calcium 5 assay	ic50	0.0191	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-phenylpropanoic acid	1813945: Agonist activity at wild type CMKL1 (unknown origin) expressed in COS-7 cells assessed as increase in calcium flux measured for 40 sec by Fluo-2 AM dye based assay	ec50	0.0199	uM
N-[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-4-yl]acetamide	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0220	uM
[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-4-yl]methanol	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0240	uM
2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-N-(2-hydroxyethyl)-N-methyl-1,3-benzoxazole-4-carboxamide	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0260	uM
2-N-butyl-2-N-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazole-2,4-diamine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0270	uM
N-butyl-4-(methoxymethyl)-N-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0290	uM
(2S)-2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-N-[(2S)-1-[[(2S)-1-(benzylamino)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]pentanediamide	1813945: Agonist activity at wild type CMKL1 (unknown origin) expressed in COS-7 cells assessed as increase in calcium flux measured for 40 sec by Fluo-2 AM dye based assay	ec50	0.0316	uM
(2R)-3-phenyl-2-[[3-(pyridin-3-ylmethoxy)benzoyl]amino]propanoic acid	2066343: Agonist activity at eYFP-tagged human CMKLR1 expressed in TAMRA-labeled chemerin-9 stimulated HEK293 cells assessed as CMKLR1 internalization by fluorescence based analysis	ec50	0.0316	uM
3-[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-5-yl]-1,1-dimethylurea	1570403: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	ic50	0.0320	uM
3-[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-4-yl]-1,1-dimethylurea	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0320	uM
1-[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-5-yl]-3-methylurea	1570403: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	ic50	0.0340	uM
(3S)-3-[4-[[1-cyclopentyl-3-[3,5-dichloro-4-(hydroxymethyl)phenyl]-4-fluoroindazol-6-yl]methoxy]phenyl]butanoic acid	2020903: Antagonist activity at human CMKLR1 expressed in CHO-K1 cells co-expressing Galpha-16 assessed as change in intracellular calcium concentration incubated for 30 mins in presence of chemerin-9 by FLIPR calcium 5 assay	ic50	0.0363	uM
[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-5-yl]urea	1570403: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	ic50	0.0370	uM
2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-N-methyl-1,3-benzoxazole-5-carboxamide	1570403: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	ic50	0.0380	uM
(3S)-3-[4-[[1-cyclopentyl-3-[3,5-dichloro-4-(hydroxymethyl)phenyl]indazol-6-yl]methoxy]phenyl]butanoic acid	2020903: Antagonist activity at human CMKLR1 expressed in CHO-K1 cells co-expressing Galpha-16 assessed as change in intracellular calcium concentration incubated for 30 mins in presence of chemerin-9 by FLIPR calcium 5 assay	ic50	0.0389	uM
1-[[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-5-yl]methyl]-3-methylurea	1570403: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	ic50	0.0480	uM
2-[[(1R)-1-[4-[5-chloro-2-(hexylcarbamoyl)phenyl]phenyl]ethyl]-(cyclopropylmethyl)amino]-5-cyclopropyl-N-cyclopropylsulfonyl-1,3-thiazole-4-carboxamide	1901253: Inhibition of human ChemR23 expressed in CAL-1 cells assessed as reduction in chemerin-induced calcium signaling	ic50	0.0500	uM
N-butyl-N-[(1R)-1-[4-[5-methyl-2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0530	uM
(3S)-3-[4-[[1-cyclopentyl-3-[3,5-difluoro-4-(hydroxymethyl)phenyl]indazol-6-yl]methoxy]phenyl]butanoic acid	2020903: Antagonist activity at human CMKLR1 expressed in CHO-K1 cells co-expressing Galpha-16 assessed as change in intracellular calcium concentration incubated for 30 mins in presence of chemerin-9 by FLIPR calcium 5 assay	ic50	0.0537	uM
N-butyl-N-[(1R)-1-[4-[4-fluoro-2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0570	uM
2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-N-ethyl-N-methyl-1,3-benzoxazole-4-carboxamide	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0620	uM
(4R,7S,10S,13S,16S,19R)-19-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-16-(3-amino-3-oxopropyl)-7,13-dibenzyl-10-methyl-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxylic acid	1813945: Agonist activity at wild type CMKL1 (unknown origin) expressed in COS-7 cells assessed as increase in calcium flux measured for 40 sec by Fluo-2 AM dye based assay	ec50	0.0640	uM
N-butyl-N-[(1R)-1-[4-[5-chloro-2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0650	uM
N-butyl-N-[(1R)-1-[4-[5-fluoro-2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.0750	uM
N-butyl-N-[(1R)-1-[4-[3-fluoro-2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.1000	uM
2-[[(1R)-1-[4-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxymethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]-5-chlorophenyl]phenyl]ethyl]-(cyclopropylmethyl)amino]-5-cyclopropyl-N-cyclopropylsulfonyl-1,3-thiazole-4-carboxamide	1901253: Inhibition of human ChemR23 expressed in CAL-1 cells assessed as reduction in chemerin-induced calcium signaling	ic50	0.1000	uM
(3S)-3-[4-[[1-cyclopentyl-3-(3,5-difluoro-4-hydroxyphenyl)-4-fluoroindazol-6-yl]methoxy]phenyl]butanoic acid	2020903: Antagonist activity at human CMKLR1 expressed in CHO-K1 cells co-expressing Galpha-16 assessed as change in intracellular calcium concentration incubated for 30 mins in presence of chemerin-9 by FLIPR calcium 5 assay	ic50	0.1096	uM
N-butyl-N-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1570403: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	ic50	0.1100	uM
2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-N-methyl-1,3-benzoxazole-4-carboxamide	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.1100	uM
N-butyl-4-pyridin-2-yl-N-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]-1,3-benzoxazol-2-amine	1722134: Inhibition of chemR23 in human CAL1 cells assessed as inhibition of chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by human chemerin addition by FDSS6000 analysis	ic50	0.1100	uM
2-[2-[butyl-[(1R)-1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethyl]amino]-1,3-benzoxazol-5-yl]-N-methylacetamide	1570403: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	ic50	0.1200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression, decreases expression	2
Rotenone	increases expression	2
Zinc	decreases expression, affects cotreatment, affects expression	2
GSK-J4	decreases expression	1
Asian ginseng	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects methylation	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
beta-hydroxy simvastatin acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases response to substance, increases expression	1
Diethylhexyl Phthalate	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects binding, increases expression	1
Lead	affects methylation	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Naled	affects expression	1
Niclosamide	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	increases expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1

ChEMBL screening assays

58 unique, capped per target: 37 binding, 21 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3362288	Binding	Agonist activity at human CMKLR1 assessed as melanophore absorbance by summary (Abse5) assay	Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). — Bioorg Med Chem Lett
CHEMBL4368341	Functional	Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition	The discovery and optimization of a series of 2-aminobenzoxazole derivatives as ChemR23 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7WQ	Abcam Raji CMKLR1 KO	Cancer cell line	Male
CVCL_B9X9	Abcam THP-1 CMKLR1 KO	Cancer cell line	Male
CVCL_C6Z6	Abcam PC-3 CMKLR1 KO	Cancer cell line	Male
CVCL_H413	CHO-K1/CMKLR1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU94	cAMP Hunter CHO-K1 CMKLR1 Gi	Spontaneously immortalized cell line	Female
CVCL_KW71	PathHunter CHO-K1 CMKLR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA07	PathHunter U2OS CMKLR1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZK06	Tango CMKLR1-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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