CCRL2

Summary

CCRL2 (C-C motif chemokine receptor like 2, HGNC:1612) is a protein-coding gene on chromosome 3p21.31, encoding C-C chemokine receptor-like 2 (O00421). Receptor for CCL19 and chemerin/RARRES2.

This gene encodes a chemokine receptor like protein, which is predicted to be a seven transmembrane protein and most closely related to CCR1. Chemokines and their receptors mediated signal transduction are critical for the recruitment of effector immune cells to the site of inflammation. This gene is expressed at high levels in primary neutrophils and primary monocytes, and is further upregulated on neutrophil activation and during monocyte to macrophage differentiation. The function of this gene is unknown. This gene is mapped to the region where the chemokine receptor gene cluster is located.

Source: NCBI Gene 9034 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• MANE Select transcript: NM_003965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1612
Approved symbol	CCRL2
Name	C-C motif chemokine receptor like 2
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	HCR, CRAM-B, CKRX, CRAM-A, ACKR5
Ensembl gene	ENSG00000121797
Ensembl biotype	protein_coding
OMIM	608379
Entrez	9034

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000357392, ENST00000399036, ENST00000400880, ENST00000400882, ENST00000433848, ENST00000441909, ENST00000495870, ENST00000909474, ENST00000909475, ENST00000909476, ENST00000909477

RefSeq mRNA: 2 — MANE Select: NM_003965 NM_001130910, NM_003965

CCDS: CCDS43079, CCDS46814

Canonical transcript exons

ENST00000399036 — 2 exons

Exon	Start	End
ENSE00001750078	46407259	46407502
ENSE00003677771	46408068	46409523

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 82.27.

FANTOM5 (CAGE): breadth broad, TPM avg 13.7514 / max 1132.6543, expressed in 523 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36475	5.9759	401
36478	1.2637	100
36472	1.2581	189
36477	1.1893	101
36476	1.1174	176
36470	0.8883	69
36469	0.5367	60
36474	0.4881	128
36468	0.2792	50
36471	0.2344	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	82.27	gold quality
rectum	UBERON:0001052	82.19	gold quality
upper lobe of left lung	UBERON:0008952	82.18	gold quality
upper lobe of lung	UBERON:0008948	81.64	gold quality
type B pancreatic cell	CL:0000169	80.83	gold quality
omental fat pad	UBERON:0010414	80.80	gold quality
olfactory bulb	UBERON:0002264	80.70	gold quality
peritoneum	UBERON:0002358	80.69	gold quality
colonic mucosa	UBERON:0000317	80.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	79.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.70	gold quality
vermiform appendix	UBERON:0001154	79.64	gold quality
monocyte	CL:0000576	79.35	gold quality
right lung	UBERON:0002167	79.18	gold quality
leukocyte	CL:0000738	78.95	gold quality
mononuclear cell	CL:0000842	78.91	gold quality
granulocyte	CL:0000094	78.85	gold quality
lung	UBERON:0002048	78.52	gold quality
spleen	UBERON:0002106	78.09	gold quality
bone marrow cell	CL:0002092	77.96	gold quality
duodenum	UBERON:0002114	77.68	gold quality
bone marrow	UBERON:0002371	77.28	gold quality
gall bladder	UBERON:0002110	77.07	gold quality
caecum	UBERON:0001153	76.01	gold quality
transverse colon	UBERON:0001157	75.57	gold quality
visceral pleura	UBERON:0002401	75.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.37	gold quality
epithelial cell of pancreas	CL:0000083	75.09	silver quality
blood	UBERON:0000178	74.73	gold quality
amniotic fluid	UBERON:0000173	74.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	432.64
E-ANND-3	yes	14.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2

miRNA regulators (miRDB)

24 targeting CCRL2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255
HSA-MIR-7975	95.04	66.76	516
HSA-MIR-3713	94.12	60.05	70
HSA-MIR-937-3P	83.52	63.05	13

Literature-anchored findings (GeneRIF, showing 12)

• CCRL2 expression is up-regulated on synovial neutrophils of rheumatoid arthritis patients (PMID:15188357)
• Results identify chemerin as a natural nonsignaling protein ligand for both human and mouse CCRL2. (PMID:18794339)
• demonstration that the homeostatic chemokine CCL19 is a specific ligand for CRAM (PMID:20002784)
• Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect pneumocystis pneumonia through immune regulation and inducing inflammation. (PMID:22046140)
• these results suggest for the first time that elevated CCRL2 in glioma promotes cell migration and invasion. (PMID:23142225)
• CCRL2 inhibited the growth of breast cancer cells in vitro and in vivo. (PMID:26487662)
• in breast cancer, CRAM-A becomes specifically upregulated under inflammatory stimuli and may serve as a potential marker of immune response. (PMID:26563945)
• CCRL2 mRNA was not significantly changed in murine and human non-alcoholic steatohepatitis liver. CCRL2 mRNA levels were positively correlated with inflammation, fibrosis and NASH scores in the patients. (PMID:28600126)
• The Atypical Receptor CCRL2 Is Essential for Lung Cancer Immune Surveillance. (PMID:31484658)
• C-C Chemokine receptor-like 2 (CCRL2) acts as coreceptor for human immunodeficiency virus-2. (PMID:33253374)
• Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1. (PMID:33373444)
• Studies with neutralizing antibodies suggest CXCL8-mediated neutrophil activation is independent of C-C motif chemokine receptor-like 2 (CCRL2) ligand binding function. (PMID:36662882)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccr11.1	ENSDARG00000070755
danio_rerio	ccr2	ENSDARG00000079829
danio_rerio	cabz01093075.1	ENSDARG00000086616
danio_rerio	ccr8.1	ENSDARG00000095789
danio_rerio	si:ch211-207g17.3	ENSDARG00000105363
danio_rerio	si:cabz01093077.1	ENSDARG00000105467
mus_musculus	Ccrl2	ENSMUSG00000043953
rattus_norvegicus	Ccrl2	ENSRNOG00000033234

Paralogs (23): CCR6 (ENSG00000112486), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-C chemokine receptor-like 2 — O00421 (reviewed: O00421)

Alternative names: Chemokine receptor CCR11, Chemokine receptor X, Putative MCP-1 chemokine receptor

All UniProt accessions (3): B2R8C0, C9JP23, O00421

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for CCL19 and chemerin/RARRES2. Does not appear to be a signaling receptor, but may have a role in modulating chemokine-triggered immune responses by capturing and internalizing CCL19 or by presenting RARRES2 ligand to CMKLR1, a functional signaling receptors. Plays a critical role for the development of Th2 responses.

Subcellular location. Cell membrane.

Tissue specificity. Expressed abundantly in immunal tissues such as spleen, fetal liver, lymph node and bone marrow. Strong expression also in lung and heart. Expressed in almost all hematopoietic cells including monocytes, macrophages, PMNs, T-cells (both CD4+ and CD8+), monocyte-derived iDCs, NK cells, and CD34+ progenitor cells. B-cells expressed isoform 1 but not isoform 2. Up-regulated on synovial neutrophils of rheumatoid arthritis patients.

Domain organisation. Lacks the conserved DRYLAIV motif in the second intracellular loop that is required for signaling of functional chemokine receptors.

Induction. Up-regulated by CCL5 on the pre-B-cell lines NALM-6 and G2.

Miscellaneous. It was initially reported that CCRL2 responds functionally to CCL2, CCL5, CCL7, and CCL8 via intracellular calcium mobilization and transwell chemotaxis although no evidence for a direct ligand-receptor interaction was provided in this report. These results are now controversial, and other studies failed to confirm CCRL2 recognition and transwell chemotaxis of these chemokines or a series of other CC- and CXC-chemokines using CCRL2-transfected cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O00421-1	1, CRAM-B	yes
O00421-2	2, CRAM-A

RefSeq proteins (2): NP_001124382, NP_003956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (30 total): topological domain 8, transmembrane region 7, sequence variant 4, sequence conflict 4, compositionally biased region 2, chain 1, region of interest 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00421-F1	77.93	0.35

Functional residue map

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

Disulfide bonds (1): 103–181

Glycosylation sites (1): 3

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 272 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_RECEPTOR_BINDING, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, ZHAN_MULTIPLE_MYELOMA_HP_UP, DORSEY_GAB2_TARGETS, PETROVA_ENDOTHELIUM_LYMPHATIC_VS_BLOOD_DN, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, CUI_TCF21_TARGETS_2_DN, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (9): chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), cell chemotaxis (GO:0060326), signal transduction (GO:0007165), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (7): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), chemokine receptor binding (GO:0042379), CCR chemokine receptor binding (GO:0048020), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
chemokine binding	2
cellular anatomical structure	2
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
regulation of biological quality	1
intracellular signaling cassette	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
G protein-coupled chemoattractant receptor activity	1
cytokine receptor activity	1
chemokine-mediated signaling pathway	1
chemokine receptor activity	1
C-C chemokine binding	1
G protein-coupled receptor binding	1
cytokine receptor binding	1
chemokine receptor binding	1
transmembrane signaling receptor activity	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

2364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCRL2	CCL20	P78556	999
CCRL2	RARRES2	Q99969	996
CCRL2	DEFB4A	O15263	994
CCRL2	CCL2	P13500	990
CCRL2	CCL19	Q99731	990
CCRL2	DEFB1	P60022	989
CCRL2	CXCL16	Q9H2A7	976
CCRL2	CCR2	P41597	969
CCRL2	DEFB103A	P81534	967
CCRL2	CCL5	P13501	962
CCRL2	CXCL9	Q07325	945
CCRL2	CCL3	P10147	942
CCRL2	CCL4	P13236	910
CCRL2	CCL17	Q92583	900
CCRL2	CCL21	O00585	890

IntAct

111 interactions, top by confidence:

A	B	Type	Score
CCRL2	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF11	CCRL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
MAST1	CCRL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
CCRL2	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (14): AMY1C (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), CST4 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), GPR89B (Affinity Capture-MS), CST1 (Affinity Capture-MS), CST4 (Affinity Capture-MS), FITM2 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), C4orf3 (Two-hybrid), CST4 (Affinity Capture-MS), FITM2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IM31, A0A0R4IP11, E9QJ73, F8VQN3, O00270, O00421, O15218, O35457, O97663, P31392, P32302, P34997, P43142, P49685, Q04683, Q0II78, Q0VDU3, Q149R9, Q16570, Q3ZC80, Q67ES2, Q6XKD3, Q75ZH0, Q7TMA4, Q7TQA9, Q7TQP4, Q7TSN5, Q7TSN6, Q863H8, Q8BZR0, Q8TDV2, Q95LF2, Q95LF3, Q95LF4, Q95LF5, Q95LF7, Q95LF9, Q95LG5, Q96CH1, Q96G91

Diamond homologs: A6QNL7, O00421, O00574, O00590, O08556, O09027, O18793, O35210, O35457, O54814, O55193, O62743, O77590, O97665, O97878, O97879, O97880, O97881, O97882, O97883, O97962, O97975, P25095, P25104, P29089, P29754, P29755, P30555, P32246, P35411, P41597, P43240, P46094, P49238, P51675, P51676, P51677, P51678, P51679, P51680

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	62.1×	6e-07
Unblocking of NMDA receptors, glutamate binding and activation	5	59.1×	6e-07
Negative regulation of NMDA receptor-mediated neuronal transmission	5	59.1×	6e-07
Assembly and cell surface presentation of NMDA receptors	10	55.2×	1e-13
Dopamine Neurotransmitter Release Cycle	5	54.0×	8e-07
Long-term potentiation	5	51.7×	9e-07
Neurexins and neuroligins	11	47.1×	5e-14
Protein-protein interactions at synapses	7	40.4×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	74.7×	1e-12
protein localization to synapse	6	65.7×	3e-08
receptor clustering	7	62.4×	3e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	49.6×	1e-08
cell-cell adhesion	9	13.1×	2e-06
regulation of small GTPase mediated signal transduction	5	10.3×	3e-03
protein-containing complex assembly	6	9.8×	1e-03
protein localization to plasma membrane	6	9.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

566 predictions. Top by Δscore:

Variant	Effect	Δscore
3:46408063:CACA:C	acceptor_loss	1.0000
3:46408066:A:T	acceptor_loss	1.0000
3:46408067:G:GC	acceptor_loss	1.0000
3:46408067:GGGCA:G	acceptor_gain	1.0000
3:46407297:T:G	donor_gain	0.9900
3:46407297:T:TG	donor_gain	0.9900
3:46407301:G:GG	donor_gain	0.9900
3:46407500:GTG:G	donor_gain	0.9900
3:46408066:A:AG	acceptor_gain	0.9900
3:46408066:AG:A	acceptor_gain	0.9900
3:46408067:G:GG	acceptor_gain	0.9900
3:46408067:GG:G	acceptor_gain	0.9900
3:46408067:GGGC:G	acceptor_gain	0.9900
3:46407200:G:T	donor_gain	0.9800
3:46407290:G:GT	donor_gain	0.9800
3:46407290:G:T	donor_gain	0.9800
3:46407293:GCTTT:G	donor_gain	0.9800
3:46407499:AGTGG:A	donor_loss	0.9800
3:46407500:GTGGT:G	donor_loss	0.9800
3:46407503:G:GA	donor_loss	0.9800
3:46407503:G:GG	donor_gain	0.9800
3:46407504:T:TC	donor_loss	0.9800
3:46407280:G:GT	donor_gain	0.9700
3:46407740:T:G	acceptor_gain	0.9500
3:46407300:A:AG	donor_gain	0.9400
3:46407313:A:AG	donor_gain	0.9400
3:46407314:G:GG	donor_gain	0.9400
3:46408066:AGG:A	acceptor_gain	0.9400
3:46408067:GGG:G	acceptor_gain	0.9400
3:46407505:A:AG	donor_loss	0.9300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000252827 (3:46407759 A>G), RS1000706663 (3:46408003 G>C), RS1001531531 (3:46405930 G>A,C), RS1002182790 (3:46406206 A>G,T), RS1004530299 (3:46409371 G>A,C), RS1004548628 (3:46408283 A>C), RS1005611643 (3:46407434 C>T), RS1006662228 (3:46406894 C>T), RS1007765591 (3:46407750 A>G), RS1008235646 (3:46407571 C>T), RS1009185227 (3:46408975 T>C,G), RS1010393860 (3:46407738 C>T), RS1011742821 (3:46407233 G>A,C), RS1013266474 (3:46406129 T>C), RS1013313781 (3:46409374 G>A)

Disease associations

OMIM: gene MIM:608379 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000612_32	Celiac disease	3.000000e-17
GCST001060_6	AIDS progression	5.000000e-06
GCST002665_3	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2.000000e-13
GCST003183_2	Setpoint viral load in HIV-1 infection	2.000000e-19
GCST004133_35	Ulcerative colitis	2.000000e-06
GCST004609_110	Monocyte percentage of white cells	3.000000e-09
GCST006976_31	Macular thickness	4.000000e-19
GCST008758_38	Pre-treatment viral load in HIV-1 infection	1.000000e-15
GCST90002389_17	Lymphocyte percentage of white cells	1.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0000180	HIV-1 infection
EFO:0007989	monocyte percentage of leukocytes
EFO:0010125	viral load
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2321627 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
CCL19	Agonist	7.36	pIC50

Binding affinities (BindingDB)

157 measured of 160 human assays (160 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[1-[4-(3-hydroxy-2-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	4 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(3,6-dihydro-2H-pyran-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	5 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-(4-pyridin-3-ylcyclohexyl)azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	5 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-(4-pyridin-2-ylcyclohexyl)azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	5 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(5-hydroxy-2-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	6 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(3-methoxy-4-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	6 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(2-hydroxyphenyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	7 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]-2-[[2-propan-2-yl-6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	7 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]-2-[[2-methyl-6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	8 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxy-2-methylpropyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	9 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-(4-ethenylcyclohexyl)azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	9 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(2,5-dihydrofuran-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	9 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
4-[[2-[[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]amino]-2-oxoethyl]amino]-6-(trifluoromethyl)quinoline-2-carboxamide	IC50	9 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(5-amino-2-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	9 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)cinnolin-4-yl]amino]acetamide	IC50	9.2 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(6-oxopiperidin-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	10 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxy-2-methylsulfanylethyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	10 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxy-2-methylpropyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	10 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	10 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(6-methyl-3-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	11 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(6-oxo-2,3-dihydro-1H-pyridin-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	12 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxybutyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	13 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
ethyl 4-[3-[[2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetyl]amino]azetidin-1-yl]cyclohexane-1-carboxylate	IC50	13 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	13 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(ethoxymethyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	14 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-[cyclopropyl(hydroxy)methyl]cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	14 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(oxan-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	15 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(2-oxo-1-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	15 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxypropyl)cyclohexyl]azetidin-3-yl]-2-[[7-(trifluoromethyl)phthalazin-1-yl]amino]acetamide	IC50	15 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-(4-hydroxy-4-phenylcyclohexyl)azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	15 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-(4-phenylcyclohexyl)azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	15 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(2-azido-1-hydroxyethyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	16 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxybut-3-enyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	16 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxyprop-2-enyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	16 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinolin-4-yl]amino]acetamide	IC50	17 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(3-amino-2-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	17 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(6-methoxy-3-pyridinyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	19 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-[hydroxy(1,3-thiazol-5-yl)methyl]cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	19 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(2-hydroxyethyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	19 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]-2-[[7-(trifluoromethyl)phthalazin-1-yl]amino]acetamide	IC50	20 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]-2-[[7-(trifluoromethyl)isoquinolin-1-yl]amino]acetamide	IC50	20 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(5-oxopyrrolidin-2-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	21 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(2-cyanophenyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	21 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxypropyl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	21 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-[cyclopropyl(hydroxy)methyl]cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	22 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(2-propan-2-yl-1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	22 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-hydroxy-4-(1,2-thiazol-5-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	22 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxy-2-methylpropyl)cyclohexyl]azetidin-3-yl]-2-[[7-(trifluoromethyl)phthalazin-1-yl]amino]acetamide	IC50	22 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
N-[1-[4-(1-hydroxycyclopent-3-en-1-yl)cyclohexyl]azetidin-3-yl]-2-[[6-(trifluoromethyl)quinazolin-4-yl]amino]acetamide	IC50	23 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2
2-[[2-cyano-6-(trifluoromethyl)quinolin-4-yl]amino]-N-[1-[4-hydroxy-4-(1,3-thiazol-5-yl)cyclohexyl]azetidin-3-yl]acetamide	IC50	23 nM	US-9062048: Cyclohexyl-azetidinyl antagonists of CCR2

ChEMBL bioactivities

164 potent at pChembl≥5 of 165 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL3704025
8.30	IC50	5	nM	CHEMBL3704026
8.30	IC50	5	nM	CHEMBL3704082
8.30	IC50	5	nM	CHEMBL3704083
8.22	IC50	6	nM	CHEMBL3704084
8.22	IC50	6	nM	CHEMBL3704085
8.15	IC50	7	nM	CHEMBL3704086
8.15	IC50	7	nM	CHEMBL3906803
8.10	IC50	8	nM	CHEMBL3659055
8.10	IC50	8	nM	CHEMBL3966845
8.05	IC50	9	nM	CHEMBL3704027
8.05	IC50	9	nM	CHEMBL3704028
8.05	IC50	9	nM	CHEMBL3704029
8.05	IC50	9	nM	CHEMBL3704079
8.05	IC50	9	nM	CHEMBL3704087
8.04	IC50	9.2	nM	CHEMBL3659041
8.00	IC50	10	nM	CHEMBL3659056
8.00	IC50	10	nM	CHEMBL3704032
8.00	IC50	10	nM	CHEMBL3704037
8.00	IC50	10	nM	CHEMBL2315922
7.96	IC50	11	nM	CHEMBL3704092
7.92	IC50	12	nM	CHEMBL3704030
7.89	IC50	13	nM	CHEMBL2315922
7.89	IC50	13	nM	CHEMBL3704101
7.89	IC50	13	nM	CHEMBL3704116
7.85	IC50	14	nM	CHEMBL3659057
7.85	IC50	14	nM	CHEMBL3704115
7.82	IC50	15	nM	CHEMBL3704033
7.82	IC50	15	nM	CHEMBL3704073
7.82	IC50	15	nM	CHEMBL2315921
7.82	IC50	15	nM	CHEMBL2315920
7.82	IC50	15	nM	CHEMBL3659045
7.80	IC50	16	nM	CHEMBL3704038
7.80	IC50	16	nM	CHEMBL3704102
7.80	IC50	16	nM	CHEMBL3704103
7.77	IC50	17	nM	CHEMBL3985434
7.77	IC50	17	nM	CHEMBL3923056
7.72	IC50	19	nM	CHEMBL3704093
7.72	IC50	19	nM	CHEMBL3704110
7.72	IC50	19	nM	CHEMBL3704117
7.70	IC50	20	nM	CHEMBL3659042
7.70	IC50	20	nM	CHEMBL3659051
7.68	IC50	21	nM	CHEMBL3704031
7.68	IC50	21	nM	CHEMBL3704089
7.68	IC50	21	nM	CHEMBL3704104
7.66	IC50	22	nM	CHEMBL3659057
7.66	IC50	22	nM	CHEMBL3704096
7.66	IC50	22	nM	CHEMBL3704097
7.66	IC50	22	nM	CHEMBL3659048
7.64	IC50	23	nM	CHEMBL3889833

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation, affects methylation, decreases methylation	2
Nickel	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
methyleugenol	increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
butyraldehyde	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Hydrogen Peroxide	affects expression	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 5 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2328025	Binding	Antagonist activity at CCR11 (unknown origin) assessed as inhibition of chemotaxis at 10 uM	1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. — Bioorg Med Chem Lett
CHEMBL2328618	Functional	Antagonist activity at CCR11 (unknown origin) assessed as inhibition of calcium flux at 10 uM	1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B7WF	Abcam Raji CCRL2 KO	Cancer cell line	Male
CVCL_B9X0	Abcam THP-1 CCRL2 KO	Cancer cell line	Male
CVCL_C6YZ	Abcam PC-3 CCRL2 KO	Cancer cell line	Male
CVCL_KW65	PathHunter CHO-K1 CCRL2 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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