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
• GTEx eGene: eQTL in 12 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.11 (intermediate), LOEUF 1.94 (unconstrained)
• MANE Select transcript: NM_003965
• Interaction hub: 2,200 STRING partners (top 6% of genes corpus-wide)
• Notable: 57 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 12 — 10 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000399036

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 1, TSL 3: 1, TSL 4: 1

ENST00000399036, ENST00000357392, ENST00000400880, ENST00000400882, ENST00000433848, ENST00000441909, ENST00000495870, ENST00000909474, ENST00000909475, ENST00000909476, ENST00000909477, ENST00001143838

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.

Highest expression (Bgee): mucosa of transverse colon, rectum, upper lobe of left lung, upper lobe of lung, type B pancreatic cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CCRL2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.8e-08	+0.33	3:46397422:T:C
Adipose Subcutaneous	eqtl	4.3e-05	+0.14	3:46437375:C:T
Skin Sun Exposed Lower leg	eqtl	4.7e-04	+0.20	3:46443082:G:A
Nerve Tibial	eqtl	4.9e-04	-0.17	3:46428968:G:C
Whole Blood	eqtl	7.3e-04	-0.41	3:46380641:C:T
Lung	eqtl	9.5e-04	+0.48	3:46387882:G:A
Brain Nucleus accumbens basal ganglia	eqtl	7.3e-03	-1.19	3:47133689:C:T
Esophagus Mucosa	eqtl	1.0e-02	-0.39	3:45586429:G:A
Colon Sigmoid	eqtl	1.8e-02	-1.04	3:46490772:AG:A
Stomach	eqtl	2.7e-02	+0.55	3:46433496:CT:C
Pituitary	eqtl	3.2e-02	+0.37	3:46226851:A:G
Heart Left Ventricle	eqtl	3.6e-02	-0.14	3:46429223:A:G

FANTOM5 promoters

showing 10 of 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

showing 100 of 288 tissues 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
small intestine	UBERON:0002108	74.34	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.94	gold quality
adipose tissue	UBERON:0001013	73.51	gold quality
smooth muscle tissue	UBERON:0001135	73.22	gold quality
connective tissue	UBERON:0002384	72.93	gold quality
intestine	UBERON:0000160	72.04	gold quality
diaphragm	UBERON:0001103	71.58	gold quality
large intestine	UBERON:0000059	71.48	gold quality
lower lobe of lung	UBERON:0008949	71.47	silver quality
lymph node	UBERON:0000029	71.14	gold quality
ileal mucosa	UBERON:0000331	71.14	gold quality
colon	UBERON:0001155	71.11	gold quality
trabecular bone tissue	UBERON:0002483	71.01	gold quality
jejunal mucosa	UBERON:0000399	70.88	gold quality
parotid gland	UBERON:0001831	70.45	gold quality
CA1 field of hippocampus	UBERON:0003881	69.37	gold quality
islet of Langerhans	UBERON:0000006	69.23	gold quality
cartilage tissue	UBERON:0002418	69.10	gold quality
triceps brachii	UBERON:0001509	68.28	gold quality
mucosa of stomach	UBERON:0001199	68.16	gold quality
apex of heart	UBERON:0002098	67.85	gold quality
pleura	UBERON:0000977	67.80	gold quality
gluteal muscle	UBERON:0002000	67.69	gold quality
heart left ventricle	UBERON:0002084	67.32	gold quality
left coronary artery	UBERON:0001626	67.09	gold quality
cardiac muscle of right atrium	UBERON:0003379	67.04	gold quality
left ventricle myocardium	UBERON:0006566	66.92	gold quality
cardiac ventricle	UBERON:0002082	66.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.52	gold quality
hair follicle	UBERON:0002073	66.36	gold quality
myocardium	UBERON:0002349	66.13	gold quality
colonic epithelium	UBERON:0000397	66.01	gold quality
coronary artery	UBERON:0001621	65.79	gold quality
superficial temporal artery	UBERON:0001614	65.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	65.66	gold quality
heart	UBERON:0000948	65.38	gold quality
body of stomach	UBERON:0001161	65.18	gold quality
right coronary artery	UBERON:0001625	65.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.51	gold quality
parietal pleura	UBERON:0002400	64.44	gold quality
sigmoid colon	UBERON:0001159	64.43	gold quality
pancreas	UBERON:0001264	64.23	gold quality
vastus lateralis	UBERON:0001379	64.11	gold quality
descending thoracic aorta	UBERON:0002345	63.88	gold quality
epithelium of nasopharynx	UBERON:0001951	63.86	gold quality
right atrium auricular region	UBERON:0006631	63.85	gold quality
quadriceps femoris	UBERON:0001377	63.84	gold quality
cardiac atrium	UBERON:0002081	63.70	gold quality
gastrocnemius	UBERON:0001388	62.94	gold quality
stomach	UBERON:0000945	62.89	gold quality
thoracic aorta	UBERON:0001515	62.82	gold quality
placenta	UBERON:0001987	62.80	gold quality
ascending aorta	UBERON:0001496	62.72	gold quality
Brodmann (1909) area 46	UBERON:0006483	62.60	gold quality
muscle of leg	UBERON:0001383	62.57	gold quality
muscle organ	UBERON:0001630	62.53	gold quality
spinal cord	UBERON:0002240	62.53	gold quality
body of pancreas	UBERON:0001150	62.21	gold quality
urinary bladder	UBERON:0001255	62.16	gold quality
left adrenal gland cortex	UBERON:0035825	62.16	gold quality
tibial nerve	UBERON:0001323	61.96	gold quality
muscle tissue	UBERON:0002385	61.76	gold quality
endocervix	UBERON:0000458	61.56	gold quality
left adrenal gland	UBERON:0001234	61.40	gold quality
left uterine tube	UBERON:0001303	61.26	gold quality
pericardium	UBERON:0002407	61.05	silver quality
muscle layer of sigmoid colon	UBERON:0035805	60.94	gold quality
mucosa of urinary bladder	UBERON:0001259	60.72	gold quality
body of uterus	UBERON:0009853	60.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.58	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lung	tissue	11.7	medium
Small intestine	tissue	11.4	medium
Duodenum	tissue	11.0	high
Colon	tissue	10.8	high
Appendix	tissue	10.8	high
Rectum	tissue	9.8	medium
Bone marrow	tissue	8.5	low
Spleen	tissue	7.7	medium
Thymus	tissue	7.2
Adipose tissue	tissue	7.0	not detected
Urinary bladder	tissue	5.5	medium
Stomach 1	tissue	5.2	high
Gallbladder	tissue	5.2	medium
Periaqueductal gray	tissue	4.9
Hypothalamus	tissue	4.7
Placenta	tissue	4.7	high
Lymph node	tissue	4.6	medium
Pons	tissue	4.2
Liver	tissue	4.1	high
Spinal cord	tissue	4.1
Substantia nigra	tissue	3.7
Medulla oblongata	tissue	3.5
Tonsil	tissue	3.5	medium
Septum	tissue	3.5
Midbrain	tissue	3.4
Corpus callosum	tissue	3.2
Thalamus	tissue	2.6
Superior colliculi	tissue	2.6
Ventral forebrain	tissue	2.4
Smooth muscle	tissue	2.3	not detected
Putamen	tissue	2.3
Amygdala	tissue	2.3
Cervix	tissue	2.2	low
Hippocampal formation	tissue	1.9
Basal ganglia	tissue	1.8	not detected
Pancreas	tissue	1.5	medium
Adrenal gland	tissue	1.5	high
Prefrontal cortex	tissue	1.4
Heart muscle	tissue	1.4	high
Cerebral cortex	tissue	1.4	low
Kidney	tissue	1.4	high
Insular cortex	tissue	1.4
Choroid plexus	tissue	1.3
Retrosplenial and cingulate cortex	tissue	1.3
Breast	tissue	1.2	medium
Endometrium 1	tissue	1.2	medium
Entorhinal cortex	tissue	1.2
Olfactory bulb	tissue	1.2
Vagina	tissue	1.1	not detected
Motor cortex	tissue	1.1
Somatosensory cortex	tissue	1.1
Retrosplenial cortex	tissue	1.1
Temporal cortex	tissue	1.1
Tongue	tissue	1.0
Frontal cortex	tissue	1.0
Locus coeruleus	tissue	1.0
Caudate putamen	tissue	1.0
Occipital cortex	tissue	1.0
Hippocampus	tissue	0.9	not detected
Pituitary gland	tissue	0.8

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (4.1), Area parastriata, superior (4.0), Dorsal spinal cord (3.8), Lateral funiculus (white matter) (3.4), Ventrolateral tegmental area, A5 NE cell group (3.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2

miRNA regulators (miRDB)

Targeting CCRL2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

24 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.111, LOEUF 1.94, missense Z -0.374 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000399036 — one region, missense o/e 1.09.

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

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccr11.1	ENSDARG00000070755
danio_rerio	ccr2	ENSDARG00000079829
danio_rerio	si:ch211-207g17.3	ENSDARG00000105363
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1920904) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal hypersensitivity reaction	1
abnormal T-helper 2 physiology	1
decreased susceptibility to type I hypersensitivity reaction	1
lymph node hypoplasia	1
decreased interleukin-13 secretion	1
decreased interleukin-4 secretion	1
decreased interleukin-5 secretion	1
abnormal dendritic cell chemotaxis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Trachypithecus phayrei	O97879	100.0%	Diamond
Pongo pygmaeus	O97881	100.0%	Diamond
Pan troglodytes	P56440	100.0%	Diamond
Pan paniscus	P60574	100.0%	Diamond
Lophocebus aterrimus	P61755	100.0%	Diamond
Pongo abelii	P61756	100.0%	Diamond
Semnopithecus entellus	P61757	100.0%	Diamond
Macaca mulatta	P61813	100.0%	Diamond
Macaca fascicularis	P61814	100.0%	Diamond
Macaca nemestrina	P61815	100.0%	Diamond
Papio anubis	P68269	100.0%	Diamond
Papio hamadryas	P68270	100.0%	Diamond
Cercocebus atys	O62743	99.7%	Diamond
Trachypithecus francoisi	O97878	99.7%	Diamond
Rhinopithecus bieti	O97880	99.7%	Diamond
Rhinopithecus avunculus	O97962	99.7%	Diamond
Macaca arctoides	O97975	99.7%	Diamond
Gorilla gorilla gorilla	P56439	99.7%	Diamond
Hylobates moloch	Q95NC0	99.7%	Diamond
Theropithecus gelada	Q95NC1	99.7%	Diamond
Symphalangus syndactylus	Q95NC5	99.7%	Diamond
Nasalis larvatus	Q95NC7	99.7%	Diamond
Colobus polykomos	Q95NC8	99.7%	Diamond
Cercocebus galeritus	Q9TV49	99.7%	Diamond
Pygathrix nemaeus	O97882	99.4%	Diamond
Nomascus leucogenys	O97883	99.4%	Diamond
Chlorocebus aethiops	P56493	99.4%	Diamond
Trachypithecus johnii	Q95NC6	99.4%	Diamond
Mandrillus sphinx	Q95ND1	99.4%	Diamond
Mandrillus leucophaeus	Q95ND2	99.4%	Diamond
Chlorocebus tantalus	Q95NE8	99.4%	Diamond
Allochrocebus solatus	Q9BGN6	99.4%	Diamond
Chlorocebus pygerythrus	Q9TV42	99.4%	Diamond
Allochrocebus lhoesti	Q9XT76	99.4%	Diamond
Miopithecus talapoin	Q95NC3	99.1%	Diamond
Erythrocebus patas	Q95ND0	99.1%	Diamond
Chlorocebus sabaeus	Q9TV43	99.1%	Diamond
Cercopithecus cephus	Q9TV47	99.1%	Diamond
Cercopithecus nictitans	Q9TV45	98.6%	Diamond
Cercopithecus ascanius	Q9TV48	98.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02009	ncRNA	105377068
CCR5	protein-coding	1234
CCR2	protein-coding	729230
CCR5AS	ncRNA	102724297
LTF	protein-coding	4057
RTP3	protein-coding	83597
LRRC2	protein-coding	79442
LRRC2-AS1	ncRNA	83598
CCR3	protein-coding	1232

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Chemokines and chemotactic factors receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; primary cilium; primary cilium tip

Antibody reliability (HPA): IH approved · IF supported

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)

Type	Positions
Disulfide bond	103–181

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	3

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

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

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 (10): 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), regulation of chemokine activity (GO:1900136), 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

5 top-level categories:

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

41 GO namespaces:

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
chemokine activity	1
regulation of cytokine activity	1
regulation of receptor binding	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
plasma membrane	CC	direct assay
CCR chemokine receptor binding	MF	physical interaction
chemokine receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,200 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCRL2	CCL20	P78556	945
CCRL2	CD4	P01730	853
CCRL2	IL17A	Q16552	853
CCRL2	RARRES2	Q99969	838
CCRL2	IFNG	P01579	836
CCRL2	KLRB1	Q12918	802
CCRL2	IL23R	Q5VWK5	799
CCRL2	CCL19	Q99731	775
CCRL2	IL22	Q9GZX6	754
CCRL2	IL10	P22301	752
CCRL2	CD8A	P01732	746
CCRL2	IL2	P01585	745
CCRL2	CCL21	O00585	731
CCRL2	FOXP3	Q9BZS1	731
CCRL2	TBX21	Q9UL17	718

IntAct

Human interaction partners of CCRL2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 72 partners by confidence:

Partner	Interaction type	MIscore	Records
PATJ	direct interaction	0.440	8
MAGI2	direct interaction	0.440	5
GRIP2	direct interaction	0.440	4
DLG1	direct interaction	0.440	3
DLG4	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
GRIP1	direct interaction	0.440	3
PDZK1	direct interaction	0.440	3
SCRIB	direct interaction	0.440	3
WHRN	direct interaction	0.440	3
APBA2	direct interaction	0.440	2
DLG2	direct interaction	0.440	2
DLG3	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
IL16	direct interaction	0.440	2
LNX1	direct interaction	0.440	2
LNX2	direct interaction	0.440	2
MAGI1	direct interaction	0.440	2
MPDZ	direct interaction	0.440	2
NHERF4	direct interaction	0.440	2
AHNAK	direct interaction	0.440	1
APBA1	direct interaction	0.440	1
APBA3	direct interaction	0.440	1
ARHGAP21	direct interaction	0.440	1
ARHGEF11	direct interaction	0.440	1
ARHGEF12	direct interaction	0.440	1
CARD11	direct interaction	0.440	1
CASK	direct interaction	0.440	1
ERBIN	direct interaction	0.440	1
FRMPD1	direct interaction	0.440	1

BioGRID (14 interactions; top human partners by supporting records): CST4 (Affinity Capture-MS; 3 records), AMY1C (Affinity Capture-MS; 2 records), FITM2 (Affinity Capture-MS; 2 records), IGHA1 (Affinity Capture-MS; 2 records), C4orf3 (Two-hybrid), CST1 (Affinity Capture-MS), GPR89B (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), ZG16B (Affinity Capture-MS)

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CCL19	receptor	Signaling by Chemokines
RARRES2	receptor	Signaling by Retinoid acid

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

Genetic variants

Variant evidence for CCRL2: 57 ClinVar records (0 pathogenic / likely pathogenic); 9 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 291):

Position(s)	Effect	Δscore	Sites
3:46408065–46408067	acceptor_loss	1.0000	7
3:46407503–46407504	donor_loss	0.9900	5
3:46407297	donor_gain	0.9700
3:46407504	donor_loss	0.9600
3:46407740	acceptor_gain	0.9500
3:46407290	donor_gain	0.9100
3:46407579	acceptor_gain	0.8400
3:46407591	acceptor_gain	0.8300
3:46408870	acceptor_gain	0.8200
3:46407305	donor_gain	0.7700

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Skin Cutaneous Melanoma (TCGA)	favorable	0.000387

Disease associations

OMIM: gene MIM:608379 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST003183_2	Setpoint viral load in HIV-1 infection	2e-19
GCST006976_81	Macular thickness	4e-19
GCST000612_32	Celiac disease	3e-17
GCST008758_31	Pre-treatment viral load in HIV-1 infection	1e-15
GCST002665_3	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2e-13
GCST90002389_149	Lymphocyte percentage of white cells	1e-10
GCST004609_35	Monocyte percentage of white cells	3e-9
GCST004133_14	Ulcerative colitis	2e-6
GCST001060_6	AIDS progression	5e-6

EFO canonical traits (from GWAS)

5 canonical traits:

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 (CPIC guideline: no)

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	affects methylation, decreases methylation, increases expression, increases 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CCRL2 across ~30M SureChEMBL compounds — explore on Sugi Predict.