CCR2

Summary

CCR2 (C-C motif chemokine receptor 2, HGNC:1603) is a protein-coding gene on chromosome 3p21.31, encoding C-C chemokine receptor type 2 (P41597). Key functional receptor for CCL2 but can also bind CCL7, and CCL12.

The protein encoded by this gene is a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The encoded protein mediates agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This protein can also be a coreceptor with CD4 for HIV-1 infection. This gene is located in the chemokine receptor gene cluster region of chromosome 3.

Source: NCBI Gene 729230 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 62 total — 5 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 11 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 4
• Drug target: yes — 10 curated mechanism-of-action drugs; 17 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Constraint (gnomAD): pLI 0.05 (LoF-tolerant), LOEUF 1.82 (unconstrained)
• MANE Select transcript: NM_001123396
• Interaction hub: 3,162 STRING partners (top 2% of genes corpus-wide)
• Notable: 62 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1603
Approved symbol	CCR2
Name	C-C motif chemokine receptor 2
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CC-CKR-2, CKR2, MCP-1-R, CD192, FLJ78302
Ensembl gene	ENSG00000121807
Ensembl biotype	protein_coding
OMIM	601267
Entrez	729230

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000445132

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 4: 1, TSL 5: 1

ENST00000445132, ENST00000400888, ENST00000421659, ENST00000465202, ENST00000908302, ENST00000963442

RefSeq mRNA: 2 — MANE Select: NM_001123396 NM_001123041, NM_001123396

CCDS: CCDS43078, CCDS46813

Canonical transcript exons

ENST00000445132 — 2 exons

Exon	Start	End
ENSE00001623822	46357477	46360940
ENSE00001839982	46354111	46354177

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 97.73.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0017 / max 264.1607, expressed in 213 samples.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CCR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	9.1e-15	-0.36	3:46330813:G:C
Skin Sun Exposed Lower leg	eqtl	2.4e-13	-0.29	3:46313348:T:C
Whole Blood	eqtl	1.6e-08	-0.10	3:46297882:A:G
Whole Blood	sqtl	1.5e-05	-0.39	3:46361136:G:A
Adipose Visceral Omentum	eqtl	1.3e-03	-0.19	3:46336534:C:T
Spleen	sqtl	1.4e-03	-0.56	3:46336534:C:T
Heart Left Ventricle	eqtl	2.2e-03	-0.85	3:46153155:G:T
Brain Spinal cord cervical c-1	eqtl	7.7e-03	+0.83	3:46227037:A:ATT
Lung	eqtl	8.0e-03	-0.13	3:46313348:T:C
Thyroid	eqtl	1.3e-02	-0.12	3:46312189:T:C
Esophagus Gastroesophageal Junction	eqtl	1.7e-02	-0.17	3:46496359:C:T
Brain Substantia nigra	eqtl	2.0e-02	-2.54	3:45465955:A:G
Testis	eqtl	3.2e-02	+0.70	3:46970325:C:T

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
36448	1.7934	164
36443	0.5969	107
36449	0.1850	66
36447	0.1205	57
36445	0.0739	26
36446	0.0717	31
36444	0.0695	29
36442	0.0489	24
36441	0.0419	23

Top tissues by expression

showing 100 of 277 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.73	gold quality
mononuclear cell	CL:0000842	97.51	gold quality
leukocyte	CL:0000738	97.40	gold quality
granulocyte	CL:0000094	94.01	gold quality
blood	UBERON:0000178	89.47	gold quality
bone marrow cell	CL:0002092	87.16	gold quality
vermiform appendix	UBERON:0001154	83.29	gold quality
spleen	UBERON:0002106	81.01	gold quality
lymph node	UBERON:0000029	80.29	gold quality
trabecular bone tissue	UBERON:0002483	78.71	gold quality
bone marrow	UBERON:0002371	78.04	gold quality
caecum	UBERON:0001153	76.12	gold quality
parietal pleura	UBERON:0002400	75.31	gold quality
rectum	UBERON:0001052	74.40	gold quality
pleura	UBERON:0000977	73.54	gold quality
gall bladder	UBERON:0002110	71.80	gold quality
smooth muscle tissue	UBERON:0001135	71.23	gold quality
right coronary artery	UBERON:0001625	70.72	gold quality
duodenum	UBERON:0002114	70.49	gold quality
mucosa of transverse colon	UBERON:0004991	70.29	gold quality
visceral pleura	UBERON:0002401	70.19	gold quality
ileal mucosa	UBERON:0000331	69.52	gold quality
upper leg skin	UBERON:0004262	69.32	gold quality
palpebral conjunctiva	UBERON:0001812	68.19	gold quality
upper lobe of left lung	UBERON:0008952	67.27	gold quality
skin of hip	UBERON:0001554	67.26	gold quality
upper lobe of lung	UBERON:0008948	66.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	66.21	gold quality
small intestine	UBERON:0002108	66.15	gold quality
lung	UBERON:0002048	65.78	gold quality
right lung	UBERON:0002167	65.12	gold quality
tibialis anterior	UBERON:0001385	64.86	silver quality
colonic epithelium	UBERON:0000397	64.54	silver quality
lower lobe of lung	UBERON:0008949	64.09	gold quality
minor salivary gland	UBERON:0001830	63.35	gold quality
transverse colon	UBERON:0001157	63.25	gold quality
left uterine tube	UBERON:0001303	62.91	gold quality
pancreatic ductal cell	CL:0002079	62.72	silver quality
periodontal ligament	UBERON:0008266	62.56	silver quality
descending thoracic aorta	UBERON:0002345	62.42	gold quality
tonsil	UBERON:0002372	61.97	gold quality
intestine	UBERON:0000160	61.91	gold quality
mouth mucosa	UBERON:0003729	61.09	gold quality
saliva-secreting gland	UBERON:0001044	61.07	gold quality
left coronary artery	UBERON:0001626	60.91	gold quality
omental fat pad	UBERON:0010414	60.83	gold quality
peritoneum	UBERON:0002358	60.77	gold quality
large intestine	UBERON:0000059	60.67	gold quality
colon	UBERON:0001155	60.63	gold quality
coronary artery	UBERON:0001621	60.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	60.36	gold quality
body of stomach	UBERON:0001161	59.99	gold quality
germinal epithelium of ovary	UBERON:0001304	59.70	silver quality
calcaneal tendon	UBERON:0003701	59.58	gold quality
stomach	UBERON:0000945	59.32	gold quality
nasopharynx	UBERON:0001728	59.05	silver quality
epithelium of nasopharynx	UBERON:0001951	59.05	silver quality
mucosa of sigmoid colon	UBERON:0004993	58.80	silver quality
urinary bladder	UBERON:0001255	58.73	gold quality
fundus of stomach	UBERON:0001160	57.97	gold quality
fallopian tube	UBERON:0003889	57.70	gold quality
right lobe of thyroid gland	UBERON:0001119	57.39	gold quality
thoracic aorta	UBERON:0001515	57.04	gold quality
sigmoid colon	UBERON:0001159	56.95	gold quality
jejunal mucosa	UBERON:0000399	56.82	gold quality
aorta	UBERON:0000947	56.81	gold quality
tibial artery	UBERON:0007610	56.75	gold quality
popliteal artery	UBERON:0002250	56.74	gold quality
metanephros cortex	UBERON:0010533	56.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	56.44	gold quality
right adrenal gland	UBERON:0001233	56.28	gold quality
nasal cavity mucosa	UBERON:0001826	56.28	gold quality
ascending aorta	UBERON:0001496	56.19	gold quality
endocervix	UBERON:0000458	56.17	gold quality
right lobe of liver	UBERON:0001114	56.02	gold quality
colonic mucosa	UBERON:0000317	55.78	gold quality
vagina	UBERON:0000996	55.70	gold quality
right adrenal gland cortex	UBERON:0035827	55.68	gold quality
mucosa of stomach	UBERON:0001199	55.63	gold quality
deltoid	UBERON:0001476	55.58	silver quality
lower esophagus	UBERON:0013473	55.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	55.12	gold quality
myometrium	UBERON:0001296	55.01	gold quality
heart left ventricle	UBERON:0002084	55.01	gold quality
left adrenal gland cortex	UBERON:0035825	54.88	gold quality
esophagus	UBERON:0001043	54.81	gold quality
prostate gland	UBERON:0002367	54.68	gold quality
cardiac ventricle	UBERON:0002082	54.51	gold quality
heart	UBERON:0000948	54.47	gold quality
apex of heart	UBERON:0002098	54.20	gold quality
esophagus mucosa	UBERON:0002469	54.19	gold quality
left adrenal gland	UBERON:0001234	54.11	gold quality
mammalian vulva	UBERON:0000997	54.05	silver quality
adrenal cortex	UBERON:0001235	54.00	gold quality
epithelial cell of pancreas	CL:0000083	53.97	gold quality
adult mammalian kidney	UBERON:0000082	53.94	gold quality
adrenal gland	UBERON:0002369	53.86	gold quality
connective tissue	UBERON:0002384	53.73	gold quality
muscle tissue	UBERON:0002385	53.65	gold quality
uterine cervix	UBERON:0000002	53.51	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	12.89
E-ANND-3	yes	8.89
E-MTAB-9801	yes	5.82
E-GEOD-110499	no	644.58

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Appendix	tissue	23.1	not detected
Lymph node	tissue	10.0	medium
Spleen	tissue	8.7	medium
Smooth muscle	tissue	6.3	not detected
Duodenum	tissue	6.2	not detected
Tonsil	tissue	6.1	high
Lung	tissue	5.1	low
Small intestine	tissue	4.8	not detected
Urinary bladder	tissue	4.7	low
Stomach 1	tissue	4.4	low
Rectum	tissue	4.1	not detected
Spinal cord	tissue	4.0
Colon	tissue	3.7	not detected
Thymus	tissue	3.7
Gallbladder	tissue	2.9	low
Salivary gland	tissue	2.6	low
Breast	tissue	2.5	low
Adipose tissue	tissue	2.3	not detected
Liver	tissue	1.9	not detected
Skin 1	tissue	1.8	low
Bone marrow	tissue	1.7	medium
Substantia nigra	tissue	1.6
Adrenal gland	tissue	1.6	not detected
Olfactory bulb	tissue	1.5
Seminal vesicle	tissue	1.4
Corpus callosum	tissue	1.4
Medulla oblongata	tissue	1.3
Cervix	tissue	1.2	medium
Cerebral cortex	tissue	1.1	low
Endometrium 1	tissue	1.1	low
Superior colliculi	tissue	1.1
Prostate	tissue	1.1	low
Hippocampal formation	tissue	1.1
Periaqueductal gray	tissue	1.1
Temporal cortex	tissue	1.1
Prefrontal cortex	tissue	1.0
Heart muscle	tissue	1.0	low
Esophagus	tissue	1.0	low
Basal ganglia	tissue	1.0	low
Amygdala	tissue	1.0
Midbrain	tissue	1.0
Fallopian tube	tissue	1.0	not detected
Septum	tissue	1.0
Retrosplenial cortex	tissue	1.0
Testis	tissue	0.9	not detected
Pons	tissue	0.9
Thalamus	tissue	0.9
Hypothalamus	tissue	0.9
Cerebellum	tissue	0.9	low
Kidney	tissue	0.9	low
Entorhinal cortex	tissue	0.9
Ventral forebrain	tissue	0.9
Retrosplenial and cingulate cortex	tissue	0.9
Insular cortex	tissue	0.9
Motor cortex	tissue	0.8
Putamen	tissue	0.8
Occipital cortex	tissue	0.8
Vagina	tissue	0.7	low
Epididymis	tissue	0.7	not detected
Placenta	tissue	0.7	low

Brain sub-regions (HPA Brain Atlas): detected in 182; highest nTPM — Dorsal spinal cord (4.0), Ventral spinal cord (2.1), Blood vessel (1.4), White matter (1.4), Subiculum (1.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPG, CREB3, FOXC1, FOXM1, NFKB1, NR3C1, PPARG, RELA, ZNF160

Functional genomics

gnomAD constraint: pLI 0.0481, LOEUF 1.82, missense Z 0.926 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000445132 — one region, missense o/e 0.93.

Literature-anchored findings (GeneRIF, showing 40)

• Association of CCR2 genotype with disease progression of HIV infection (PMID:11709782)
• genotypes and their relative contribution to human immunodeficiency virus type 1 (HIV-1) seroconversion, early HIV-1 RNA concentration in plasma, and later disease progression (PMID:11752157)
• CCR2 641 allele homozygosity implicated in natural resistance to HIV-1 transmission through heterosexual contact (PMID:11873083)
• The frequencies of CCR2 mutation associated with the development of clinical symptoms upon infection with human immunodeficiency virus type 1 (HIV-1) were determined in a cohort of individuals from Moscow. (PMID:11898620)
• Most natural killer t-cells express receptors for extralymphoid tissue or inflammation-related chemokines (CCR2, CCR5, and CXCR3), while few NKT cells express lymphoid tissue-homing chemokine receptors (CCR7 and CXCR5). (PMID:12070001)
• expression of CCR2B in aiway epithelial cells after injury enhances cell migration and proliferation (PMID:12078856)
• May be a new candidate for a susceptibility locus for bone mass in middle-aged men and postmenopausal women (PMID:12079277)
• Electrostatic potential maps of human and primate CCR2b all display the dipolar characteristics of CCR2b with the negative pole located in the extracellular part and a strong positive pole in the cytoplasmic part. (PMID:12192431)
• Results show that high ambient glucose does not affect mesangial monocyte chemoattractant protein-1 release and decreases its chemokine receptor 2 (CCR2) receptor expression. (PMID:12399623)
• C-C chemokine receptor 2 and C-C chemokine receptor 5 genotypes in patients treated for chronic hepatitis C virus infection. (PMID:12403355)
• Val64Ile polymorphism in the C-C chemokine receptor 2 is associated with reduced coronary artery calcification. (PMID:12426226)
• Polymorphism is associated with myocardial infarct. (PMID:12469616)
• The specific distribution and regulation of chemokine receptors CXCR1, CXCR4, CCR5, and CCR2b in endometrial epithelium and blastocyst suggest a role for these receptors in the apposition and adhesion phases of human implantation. (PMID:12651900)
• CCR2 genotype seems to predispose patients for myocardial infarction before the age of 65 years; the higher prevalence of heart failure in gene carriers with the rare alle might be a consequence of myocardial infarction (PMID:12719858)
• activation of CCR5 and CCR2 is induced by conformational changes in the conserved TXP motif in transmembrane helix 2 (PMID:12837756)
• females with the VI genotype were seven times more prone to suffer from myocardial infarction before 50 years than those with the VV genotype (PMID:12853162)
• The calculation of the congruence revealed that 92.0% of individuals exhibited the same genotype for both CCR2-64I and CCR5-59653T polymorphisms. Our results confirm that linkage between CCR5-59653T and CCR2-64I alleles is not absolute. (PMID:12884524)
• Polymorphisms of CCR2 and CCR5 do not seem to be involved in susceptibility to systemic lupus erythematosis (PMID:12913933)
• Angiotensin II significantly stimulated superoxide formation in monocytes, as well as the chemotactic response to MCP-1 with the increased expression of monocyte chemoattractant protein 1 receptor determined by RT-PCR and western blotting analysis (PMID:13678532)
• A PCR-based genotyping method was used to determine the genetic variation at the CCR5 gene and an automated real-time Pyrosequencing technology was employed for the analysis of G right curved arrow A point mutation at the CCR2 gene (PMID:14533004)
• The presence of the CCR2-64I allele in a Japanese population seems to provide protection against the development of multiple sclerosis. (PMID:14644039)
• Our findings suggest a limited role for CCL2/CCR2 in early active multiple sclerosis (PMID:15257681)
• A decreased frequency and an absence of homozygous for the polymorphism CCR2-64I were found. (PMID:15465089)
• The impact of CCR2 on neuropathogenesis may involve alterations in inflammatory responses within the CNS rather than a direct impact on viral entry or replication. (PMID:15579296)
• Did not support previous findings of an association between CCR2 gene variability and the risk of sarcoidosis; however, linkage disequilibrium showed positive results and suggests susceptibility gene in surrounding chromosomal region. (PMID:15750046)
• Frequency distribution of CCR2-64I mutations in Brazilian Amazon region (PMID:15754978)
• subclinical clotting activation may cause an increased CCR2 gene and protein expression on uremic peripheral blood mononuclear cells, contributing to hemodialysis-related chronic microinflammation (PMID:15976001)
• These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung. (PMID:16033640)
• Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5), and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). (PMID:16055130)
• The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies. (PMID:16095529)
• potential autocrine regulation of key profibrotic properties via a CCL2/CCR2 loop in early-stage diffuse cutaneous systemic sclerosis (PMID:16320328)
• These data suggest that fibrogenic processes in Mo regulated by MCP-1/CCR2 may be novel, therapeutic targets for combating organ fibrosis. (PMID:16415174)
• results of the present study provide no evidence that either CCR5-Delta32 or CCR2-64I is associated with hypertension (PMID:16461193)
• the risk of acute rejection in renal transplantation may be associated with genetic variation in the chemokine receptor genes CCR5-59029 and CCR2V641 in Turkey (PMID:16598837)
• Our data suggest that elevated serum MCP-1 levels and increased monocyte CCR2, CD36, CD68 expression correlate with poor blood glucose control and potentially contribute to increased recruitment of monocytes to the vessel wall in diabetes mellitus. (PMID:16631114)
• Double immunofluorescense staining demonstrated that cellular sources of MCP-1/CCL2 and IP-10/CXCL10 were hypertrophic astrocytes and that both astrocytes and microglia/macrophages expressed CCR2 and CXCR3. (PMID:16733654)
• The mRNA expressions of CCR2 of all post-kidney transplant patients were significantly higher than controls. (PMID:16781696)
• In atherogenesis, oxidized lipid-driven activation of macrophage PPARgamma in the intima may result in a proadhesive chemokine receptor switch-CCR2 off. (PMID:16908772)
• evaluated the possible relation between CCR2 and CCR5 alleles and blood pressure (BP) levels in hypertensive (PMID:17060059)
• Results suggest that CCR2 may contribute to prostate cancer development. (PMID:17216598)

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	Ccr2	ENSMUSG00000049103
rattus_norvegicus	Ccr2	ENSRNOG00000063127

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), 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:106185) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 101 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired macrophage chemotaxis	7
decreased interferon-gamma secretion	3
decreased neutrophil cell number	2
decreased monocyte cell number	2
decreased inflammatory response	2
abnormal leukocyte physiology	2
abnormal leukocyte migration	2
abnormal microglial cell physiology	2
decreased macrophage cell number	2
increased eosinophil cell number	2
increased physiological sensitivity to xenobiotic	2
increased susceptibility to Coronaviridae infection	2
abnormal trabecular bone morphology	1
enlarged heart	1
abnormal response to cardiac infarction	1
enlarged liver	1
abnormal spleen morphology	1
enlarged spleen	1
weight loss	1
abnormal gait	1
abnormal osteoclast physiology	1
hepatic necrosis	1
multifocal hepatic necrosis	1
liver inflammation	1
abnormal glucose homeostasis	1

+76 more (showing top 25).

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
Meleagris gallopavo	P33396	99.7%	Diamond
Gorilla gorilla gorilla	P56439	99.7%	Diamond
Gallus gallus	P79785	99.7%	Diamond
Saimiri sciureus	Q8HZU0	99.7%	Diamond
Callithrix jacchus	Q8HZU1	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
Chlorocebus aethiops	Q9TSQ8	99.7%	Diamond
Cercocebus galeritus	Q9TV49	99.7%	Diamond
Pygathrix nemaeus	O97882	99.4%	Diamond
Nomascus leucogenys	O97883	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

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
CCR5AS	ncRNA	102724297
CCR1	protein-coding	1230
CCR3	protein-coding	1232
CCR5	protein-coding	1234
LINC02009	ncRNA	105377068
CCRL2	protein-coding	9034
LTF	protein-coding	4057

Protein

Protein identifiers

C-C chemokine receptor type 2 — P41597 (reviewed: P41597)

Alternative names: Monocyte chemoattractant protein 1 receptor

All UniProt accessions (2): E9PH76, P41597

UniProt curated annotations — full annotation on UniProt →

Function. Key functional receptor for CCL2 but can also bind CCL7, and CCL12. Also transduces signaling mediated by CCL13. Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion. Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B. Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation. Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R. Plays an important role in mediating peripheral nerve injury-induced neuropathic pain. Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B. Mediates the recruitment of macrophages and monocytes to the injury site following brain injury. (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.

Subunit / interactions. Interacts with ARRB1. Interacts (via extracellular N-terminal region) with beta-defensin DEFB106A/DEFB106B; this interaction may preferentially require specific tyrosine sulfation on CCR2. Interacts with NUP85; the interaction is required for CCR2 clusters formation on the cell membrane and CCR2 signaling. Interacts with GNAI1. (Microbial infection) Binds to HIV-1 Tat. (Microbial infection) Interacts with Kaposi virus protein vCCL2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed by monocytes and IL2-activated NK cells. Abundantly expressed on CD14+/CD16- monocytes and weakly on CD14+/CD16+ monocytes, type 2 dendritic cells (DCs) and plasmacytoid DCs (at protein level).

Post-translational modifications. N-glycosylated. Sulfation increases the affinity for both monomeric and dimeric CCL2 with stronger binding to the monomeric form. Binding of sulfated CCR2 to CCL2 promotes conversion of CCL2 from dimer to monomer.

Disease relevance. Polycystic lung disease (PCLUD) [MIM:219600] An autosomal recessive disease characterized by pulmonary alveolar proteinosis, marked peribronchovascular and parenchymal lymphocytosis, peribronchiolar pulmonary fibrosis, progressive diffuse parenchymal lung cyst formation and enlargement, progressive obstructive airflow limitation, and recurrent secondary infections. Additional features may include digital clubbing, allergies, and atopic dermatitis. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by CREB3. In NK cells, induced by IL2.

Polymorphism. Variations in CCR2 are associated with relative resistance to immunodeficiency virus type 1 (resistance to HIV-1) [MIM:609423].

Miscellaneous. Mutagenesis of Leu-316 to Thr as well as Phe-320 to Asp decrease interaction with NUP85.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P41597-1	A	yes
P41597-2	B

RefSeq proteins (2): NP_001116513, NP_001116868* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR002237	Chemokine_CCR2	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (52 total): helix 15, sequence variant 10, topological domain 8, transmembrane region 7, turn 3, modified residue 2, strand 2, chain 1, region of interest 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
7P8X	Crystal Structure of leukotoxin LukE from Staphylococcus aureus in complex with a doubly …	X-RAY DIFFRACTION	1.4
6GPX	CRYSTAL STRUCTURE OF CCR2A IN COMPLEX WITH MK-0812	X-RAY DIFFRACTION	2.7
5T1A	Structure of CC Chemokine Receptor 2 with Orthosteric and Allosteric Antagonists	X-RAY DIFFRACTION	2.81
7XA3	Cryo-EM structure of the CCL2 bound CCR2-Gi complex	ELECTRON MICROSCOPY	2.9
6GPS	CRYSTAL STRUCTURE OF CCR2A IN COMPLEX WITH MK-0812	X-RAY DIFFRACTION	3.3
2MLO	Human CCR2 Membrane-Proximal C-Terminal Region (PRO-C) in a Membrane bound form	SOLUTION NMR
2MLQ	Human CCR2 Membrane-Proximal C-Terminal Region (PRO-C) in a frount bound form	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41597-F1	78.28	0.53

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 7XA3

Human Protein Atlas

Protein class: CD markers, G-protein coupled receptors, GPCRs excl olfactory receptors, Chemokines and chemotactic factors receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; nucleoli fibrillar center

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.

Post-translational modifications (2)

Type	Positions
Sulfotyrosine	26
Phosphotyrosine	139

Disulfide bonds (1)

Type	Positions
Disulfide bond	113–190

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	14

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 17; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-1461957	Beta defensins	curated
R-HSA-380108	Chemokine receptors bind chemokines	curated
R-HSA-9968734	Differentiation of Circulating Monocytes	curated
R-HSA-418594	G alpha (i) signalling events	curated
R-HSA-6783783	Interleukin-10 signaling	curated
R-HSA-6803157	Antimicrobial peptides	—
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1461973	Defensins	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 590 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, ZHAN_LATE_DIFFERENTIATION_GENES_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_T_CELL_CHEMOTAXIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (50): blood vessel remodeling (GO:0001974), dendritic cell chemotaxis (GO:0002407), regulation of T cell cytokine production (GO:0002724), positive regulation of T-helper 1 type immune response (GO:0002827), negative regulation of type 2 immune response (GO:0002829), intracellular calcium ion homeostasis (GO:0006874), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cellular defense response (GO:0006968), negative regulation of adenylate cyclase activity (GO:0007194), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), response to wounding (GO:0009611), regulation of vascular endothelial growth factor production (GO:0010574), positive regulation of T cell chemotaxis (GO:0010820), negative regulation of angiogenesis (GO:0016525), cytokine-mediated signaling pathway (GO:0019221), sensory perception of pain (GO:0019233), calcium-mediated signaling (GO:0019722), cellular homeostasis (GO:0019725), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-2 production (GO:0032743), positive regulation of tumor necrosis factor production (GO:0032760), monocyte extravasation (GO:0035696), T-helper 17 cell chemotaxis (GO:0035705), negative regulation of eosinophil degranulation (GO:0043310), regulation of T cell differentiation (GO:0045580), positive regulation of alpha-beta T cell proliferation (GO:0046641), regulation of inflammatory response (GO:0050727), positive regulation of inflammatory response (GO:0050729), positive regulation of T cell activation (GO:0050870), positive regulation of synaptic transmission, glutamatergic (GO:0051968), cell chemotaxis (GO:0060326), chemokine-mediated signaling pathway (GO:0070098), positive regulation of monocyte chemotaxis (GO:0090026), positive regulation of immune complex clearance by monocytes and macrophages (GO:0090265), inflammatory response to wounding (GO:0090594), positive regulation of cold-induced thermogenesis (GO:0120162), positive regulation of glutamate receptor signaling pathway (GO:1900451), macrophage migration (GO:1905517), positive regulation of thymocyte migration (GO:2000412), positive regulation of monocyte extravasation (GO:2000439), positive regulation of CD8-positive, alpha-beta T cell extravasation (GO:2000451), positive regulation of astrocyte chemotaxis (GO:2000464), positive regulation of hematopoietic stem cell migration (GO:2000473), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), cellular response to cytokine stimulus (GO:0071345)

GO Molecular Function (11): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), CCR2 chemokine receptor binding (GO:0031727), chemokine (C-C motif) ligand 2 binding (GO:0035715), chemokine (C-C motif) ligand 12 binding (GO:0035716), chemokine (C-C motif) ligand 7 binding (GO:0035717), identical protein binding (GO:0042802), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), cytokine binding (GO:0019955)

GO Cellular Component (8): cytoplasm (GO:0005737), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body (GO:0043025), perikaryon (GO:0043204), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

13 top-level categories:

Category	Pathways
Immune System	2
Signaling by GPCR	2
Defensins	1
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signaling by Interleukins	1
Developmental Cell Lineages	1
Antimicrobial peptides	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Cytokine Signaling in Immune system	1
Innate Immune System	1

GO top-level categories

showing 60 of 62 GO namespaces:

Category	Terms
C-C chemokine binding	4
cellular anatomical structure	4
defense response	2
chemokine binding	2
protein binding	2
tissue remodeling	1
leukocyte chemotaxis	1
dendritic cell migration	1
T cell cytokine production	1
regulation of T cell mediated immunity	1
regulation of cytokine production involved in immune response	1
positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
regulation of T-helper 1 type immune response	1
T-helper 1 type immune response	1
regulation of type 2 immune response	1
type 2 immune response	1
negative regulation of immune response	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
adenylate cyclase activity	1
negative regulation of catalytic activity	1
regulation of adenylate cyclase activity	1
regulation of biological quality	1
cell surface receptor signaling pathway via STAT	1
response to stress	1
regulation of cytokine production	1
vascular endothelial growth factor production	1
T cell chemotaxis	1
regulation of T cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
positive regulation of T cell migration	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
sensory perception	1
intracellular signaling cassette	1
G protein-coupled chemoattractant receptor activity	1
cytokine receptor activity	1
chemokine-mediated signaling pathway	1
chemokine receptor activity	1
CCR chemokine receptor binding	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 69 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
chemokine-mediated signaling pathway	BP	direct assay
cytokine-mediated signaling pathway	BP	direct assay
positive regulation of astrocyte chemotaxis	BP	direct assay
positive regulation of monocyte chemotaxis	BP	direct assay
cytoplasm	CC	direct assay
plasma membrane	CC	direct assay
C-C chemokine receptor activity	MF	direct assay
CCR2 chemokine receptor binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,162 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR2	CCL2	P13500	958
CCR2	CCL5	P13501	879
CCR2	CCL3	P10147	841
CCR2	CCL7	P80098	841
CCR2	CD4	P01730	832
CCR2	CCL4	P13236	830
CCR2	IL6	P05231	826
CCR2	IL10	P22301	826
CCR2	CD8A	P01732	820
CCR2	IFNG	P01579	818
CCR2	CX3CL1	P78423	814
CCR2	CCL8	P78388	812
CCR2	CXCL12	P48061	810
CCR2	CD68	P34810	801
CCR2	ITGAM	P11215	777

IntAct

Human interaction partners of CCR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 46 partners by confidence:

Partner	Interaction type	MIscore	Records
POTEE	physical association	0.590	2
MET	proximity	0.420	1
SRC	proximity	0.420	1
RAMP2	physical association	0.400	3
RAMP3	physical association	0.400	2
RAMP1	physical association	0.400	1
APP	physical association	0.370	1
ARL6IP5	physical association	0.370	1
ATP2B1	physical association	0.370	1
B3GAT3	physical association	0.370	1
BLOC1S6	physical association	0.370	1
CACYBP	physical association	0.370	1
CD59	physical association	0.370	1
CD81	physical association	0.370	1
CDIP1	physical association	0.370	1
CLPTM1	physical association	0.370	1
DMWD	physical association	0.370	1
EMC10	physical association	0.370	1
ERGIC3	physical association	0.370	1
GOT1	physical association	0.370	1
GPR161	physical association	0.370	1
HERPUD1	physical association	0.370	1
HMOX2	physical association	0.370	1
JPH3	physical association	0.370	1
NDFIP1	physical association	0.370	1
NOTCH2	physical association	0.370	1
NTNG2	physical association	0.370	1
PCMT1	physical association	0.370	1
PLLP	physical association	0.370	1
PTPN9	physical association	0.370	1

BioGRID (42 interactions; top human partners by supporting records): POTEE (Affinity Capture-MS; 2 records), APP (Two-hybrid), ARL6IP5 (Two-hybrid), ATP2B1 (Two-hybrid), B3GAT3 (Two-hybrid), BLOC1S6 (Two-hybrid), CACYBP (Two-hybrid), CD59 (Two-hybrid), CD81 (Two-hybrid), CDIP1 (Two-hybrid), CLPTM1 (Two-hybrid), DMWD (Two-hybrid), EMC10 (Two-hybrid), ERGIC3 (Two-hybrid), GOT1 (Two-hybrid)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
JAK2	“up-regulates activity”	CCR2	phosphorylation
CCL2	“up-regulates activity”	CCR2	binding
CCL3	“up-regulates activity”	CCR2	binding
CCR2	“up-regulates activity”	ERK1/2	phosphorylation

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ CCR2-CXCR4 complex	2	CCR2, CXCR4
★ CCR2-CCR5 complex	2	CCR2, CCR5
★ AGTR1-CCR2 complex	2	CCR2, AGTR1
C-C chemokine receptor type 2	1	CCR2

Ligand–receptor pairs (CellPhoneDB) (6)

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

6 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CCL8	receptor	Signaling by Chemokines
CCL13	receptor	Signaling by Chemokines
CCL16	receptor	Signaling by Chemokines
CCL26	receptor	Signaling by Chemokines
CCL2	receptor	Signaling by Chemokines
CCL7	receptor	Signaling by Chemokines

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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.

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5	12.8×	7e-03
protein localization to plasma membrane	5	12.3×	7e-03

Disease & clinical

Genetic variants

Variant evidence for CCR2: 62 ClinVar records (6 pathogenic / likely pathogenic); 19 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	39
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4850565	NM_001123396.4(CCR2):c.586C>T (p.Arg196Ter)	Likely pathogenic	criteria provided, single submitter	1
3061925	NM_001123396.4(CCR2):c.641_646del (p.Pro214_Leu215del)	Pathogenic	no assertion criteria provided	1
3061926	NM_001123396.4(CCR2):c.182T>G (p.Met61Arg)	Pathogenic	no assertion criteria provided	1
3061927	NM_001123396.4(CCR2):c.887C>A (p.Thr296Asn)	Pathogenic	no assertion criteria provided	1
3061928	NM_001123396.4(CCR2):c.59_60insAC (p.Thr21fs)	Pathogenic	no assertion criteria provided	1
3061929	NM_001123396.4(CCR2):c.356T>G (p.Leu119Arg)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CCR2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 108):

Position(s)	Effect	Δscore	Sites
3:46354178–46354179	donor_loss	1.0000	5
3:46357475–46357476	acceptor_loss	1.0000	6
3:46357468	acceptor_gain	0.9600
3:46357474	acceptor_gain	0.9600
3:46354861	acceptor_gain	0.9200
3:46354860	acceptor_gain	0.9000
3:46359567	donor_gain	0.8600
3:46354182	donor_gain	0.8500
3:46354182	donor_gain	0.8300
3:46354860	acceptor_gain	0.8200

AlphaMissense

571 missense substitutions predicted likely pathogenic (of 2,361 scored), across 180 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D88	8	0.918	0.968
D137	8	0.892	0.950
N60	8	0.891	0.960
H297	8	0.764	0.925
C190	7	0.954	0.973
C113	7	0.934	0.966
C32	7	0.908	0.938
C277	7	0.877	0.921
W256	7	0.876	0.960
W165	7	0.866	0.990
W106	7	0.864	0.969
F178	7	0.861	0.953
F312	7	0.846	0.963
N301	7	0.801	0.944
F130	7	0.794	0.909
F91	7	0.789	0.890
D78	7	0.788	0.817
F108	7	0.708	0.829
P302	6	0.897	0.942
P258	6	0.893	0.970

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	5.21e-06

Disease associations

OMIM: gene MIM:601267 | disease phenotypes: MIM:219600

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	green

Mondo (1): cystic disease of lung (MONDO:0009060)

HPO phenotypes

4 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002719	Recurrent infections
HP:0004876	Spontaneous neonatal pneumothorax
HP:0005948	Multiple pulmonary cysts

GWAS associations

19 associations:

Study	Trait	p-value
GCST004609_34	Monocyte percentage of white cells	1e-33
GCST004608_73	Granulocyte percentage of myeloid white cells	2e-25
GCST005523_14	Celiac disease	1e-20
GCST000612_32	Celiac disease	3e-17
GCST005977_30	Monocyte count	7e-14
GCST002665_3	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2e-13
GCST90002393_359	Monocyte count	2e-13
GCST90002394_511	Monocyte percentage of white cells	8e-12
GCST004625_170	Monocyte count	1e-11
GCST009159_6	Blood protein levels	2e-11
GCST90002393_358	Monocyte count	5e-10
GCST003045_6	Ulcerative colitis	9e-10
GCST001762_258	Obesity-related traits	7e-9
GCST003045_39	Ulcerative colitis	1e-8
GCST008489_15	Celiac disease	3e-8
GCST010730_3	Rheumatoid arthritis	3e-8
GCST002520_6	Celiac disease	4e-8
GCST003043_190	Inflammatory bowel disease	4e-8
GCST004133_14	Ulcerative colitis	2e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004747	protein measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C563237	Cystic Disease Of Lung *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4015 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CCR2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

10 curated-mechanism drugs:

Drug	Modality	Max phase
CENICRIVIROC	Small molecule	3
AZD2423	Unknown	2
BMS-741672	Small molecule	2
BMS-813160	Small molecule	2
ILACIRNON	Small molecule	2
JNJ-41443532	Small molecule	2
MK-0812	Small molecule	2
PF-04634817	Small molecule	2
PF-4136309	Small molecule	2
PLOZALIZUMAB	Antibody	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 173,146 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

17 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL633	AMIODARONE	4	30,023
CHEMBL11359	CISPLATIN	4
CHEMBL964	DISULFIRAM	4	39,061
CHEMBL193	NIFEDIPINE	4	74,779
CHEMBL18442	PLERIXAFOR	4	11,339
CHEMBL2110727	CENICRIVIROC	3	2,245
CHEMBL38380	FASUDIL	3	12,137
CHEMBL2178578	VERCIRNON	3	352
CHEMBL4457723	BMS-741672	2	2
CHEMBL4594419	BMS-813160	2	60
CHEMBL2178573	ILACIRNON	2	452
CHEMBL2204263	JNJ-41443532	2	34
CHEMBL3305901	MK-0812	2	27
CHEMBL2029422	PF-4136309	2
CHEMBL541388	FASUDIL HYDROCHLORIDE	2	2,512
CHEMBL397647	JNJ-17166864 CATION	2	36
CHEMBL2105686	CENICRIVIROC MESYLATE	1	87

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 (31 total), top 25:

Ligand	Action	Affinity	Parameter
CCL2	Full agonist	10.2	pIC50
plozalizumab	Binding	9.72	pEC50
BMS-681	Antagonist	9.15	pIC50
vMIP-II	Antagonist	9.1	pIC50
BMS-741672	Antagonist	8.96	pIC50
compound 39 [PMID: 31742400]	Antagonist	8.8	pKi
MC148R	Antagonist	8.8	pIC50
CCL7	Full agonist	8.7	pIC50
CCL13	Full agonist	8.7	pIC50
CCL8	Full agonist	8.6	pIC50
AZD2423	Negative	8.59	pIC50
BMS-753426	Antagonist	8.57	pIC50
CCL26	Antagonist	8.5	pIC50
RS-136270	Antagonist	8.5	pIC50
INCB3284	Antagonist	8.43	pIC50
PF-04634817	Antagonist	8.43	pIC50
MK-0812	Antagonist	8.35	pIC50
ilacirnon	Antagonist	8.3	pIC50
INCB8761	Antagonist	8.28	pIC50
INCB3344	Antagonist	8.0	pIC50
CCL11	Partial agonist	7.7	pIC50
GSK Compound 34	Antagonist	7.6	pKi
TAK-779	Antagonist	7.2	pKi
vCCL4	Full agonist	7.1	pIC50
JNJ-27141491	Antagonist	7.02	pIC50

Binding affinities (BindingDB)

2006 measured of 2138 human assays (2139 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(1S,3R)-N-(3,5-bis(trifluoromethyl)benzyl )-1-isopropyl-3-(3-methyltetrahydro-2H-pyran-4-ylamino)cyclopentanecarboxamide	IC50	0.1 nM
(1S,3R)-N-{[3-fluoro-5-(trifluoromethyl)phenyl]methyl}-3-[(1S,5’R)-5’-methylspiro[indene-1,4’-piperidine]-1’-yl]-1-(propan-2-yl)cyclopentane-1-carboxamide	IC50	0.15 nM
CHEMBL3233186	IC50	0.2 nM
CHEMBL3233188	IC50	0.2 nM
N-(2-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-((4-(methylthio)phenylsulfonyl)methyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide	IC50	0.2 nM
CHEMBL258205	IC50	0.2 nM
(1S,3R)-1-cyclopropyl-N-{[3-fluoro-5-(trifluoromethyl)phenyl]methyl}-3-[(1S,5’R)-5’-methylspiro[indene-1,4’-piperidine]-1’-yl]cyclopentane-1-carboxamide	IC50	0.23 nM
CHEMBL3577945	IC50	0.24 nM
CHEMBL3263286	IC50	0.25 nM
(1S,3R)-N-(3,5-bis(trifluoromethyl)benzyl)-3-(3-ethyltetrahydro-2H-pyran-4-ylamino)-1-isopropylcyclopentanecarboxamide	IC50	0.3 nM
N-(2-((1S,2R,4R)-4-(dimethylamino)-2-((4-(methylthio)phenylsulfonyl)methyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide	IC50	0.3 nM
N-((S)-1-((1S,2R,4R)-4-(ethyl(isopropyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide	IC50	0.3 nM
CHEMBL4764460	IC50	0.3 nM
(1R,3R)-N-{[3-fluoro-5-(trifluoromethyl)phenyl]methyl}-1-(2-methylpropyl)-3-[(1S,5’R)-5’-methylspiro[indene-1,4’-piperidine]-1’-yl]cyclopentane-1-carboxamide	IC50	0.32 nM
CHEMBL3577948	IC50	0.4 nM
N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(tosylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide	IC50	0.4 nM
CHEMBL4457723	IC50	0.4 nM
(S)-1-(4-(1-(3,5-bis(trifluoromethyl)benzylamino)-1-oxo-4-(4-phenylpiperidin-1-yl)butan-2-yl)thiazol-2-yl)-3-methylurea	IC50	0.43 nM
CHEMBL4483373	KI	0.447 nM
CHEMBL3305901	KD	0.48 nM
CHEMBL3233187	IC50	0.5 nM
CHEMBL3577946	IC50	0.5 nM
N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-3-(trifluoromethyl)benzamide	IC50	0.5 nM
CHEMBL271828	IC50	0.5 nM
CHEMBL2029422	IC50	0.5 nM
CHEMBL3233184	IC50	0.6 nM
CHEMBL3577942	IC50	0.6 nM
N-{[3,5-bis(trifluoromethyl)phenyl]methyl}-2-(2-acetamido-1,3-thiazol-4-yl)-4-[(5’R)-5’-methylspiro[indene-1,4’-piperidine]-1’-yl]butanamide	IC50	0.6 nM
CHEMBL256301	IC50	0.6 nM
CHEMBL257191	IC50	0.6 nM
CHEMBL2338392	KI	0.6 nM
CHEMBL4548396	KI	0.6 nM
CHEMBL4790208	IC50	0.6 nM
CHEMBL4442783	IC50	0.67 nM
CHEMBL3233181	IC50	0.7 nM
(S)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(2-acetamidothiazol-4-yl)-4-(4-phenylpiperidin-1-yl)butanamide	IC50	0.7 nM
N-{[3,5-bis(trifluoromethyl)phenyl]methyl}-2-(2-acetamido-1,3-thiazol-4-yl)-4-{spiro[indene-1,4’-piperidine]-1’-yl}butanamide	IC50	0.7 nM
N-(2-((1S,2R,4R)-4-(diethylamino)-2-((4-(methylthio)phenylsulfonyl)methyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide	IC50	0.7 nM
1-Cyclooct-1-enylmethyl-4-[(2,7-dichloro-9H-xanthene-9-carbonyl)-amino]-1-ethyl-piperidinium; iodide	IC50	0.73 nM
CHEMBL3577933	IC50	0.8 nM
(2S)-N-{[3,5-bis(trifluoromethyl)phenyl]methyl}-2-{2-[(methylcarbamoyl)amino]-1,3-thiazol-4-yl}-4-{spiro[indene-1,4’-piperidine]-1’-yl}butanamide	IC50	0.8 nM
(1S,3R)-N-(3,5-bis(trifluoromethyl)benzyl)-3-(3-fluorotetrahydro-2H-pyran-4-ylamino)-1-isopropylcyclo pentanecarboxamide	IC50	0.8 nM
3-fluoro-N-((S)-1-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexyl)-2-oxopyrrolidin-3-yl)-5-(trifluoromethyl)benzamide	IC50	0.8 nM
N-(2-((1S,2R,4R)-4-(isopropyl(methyl)amino)-2-(phenylsulfonylmethyl)cyclohexylamino)-2-oxoethyl)-3-(trifluoromethyl)benzamide	IC50	0.8 nM
CHEMBL4781426	IC50	0.8 nM
CHEMBL256629	IC50	0.83 nM
CHEMBL4577171	KI	0.832 nM
CHEMBL4571719	KI	0.871 nM
CHEMBL271288	IC50	0.89 nM
CHEMBL2088212	IC50	0.9 nM

ChEMBL bioactivities

3174 potent at pChembl≥5 of 3267 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	IC50	0.03	nM	CHEMBL41275
10.40	IC50	0.04	nM	PLERIXAFOR
10.40	ED50	0.04	nM	CHEMBL512607
10.15	ED50	0.07	nM	CHEMBL467070
10.10	IC50	0.08	nM	CHEMBL41275
10.10	ED50	0.08	nM	CHEMBL512615
10.05	IC50	0.09	nM	PLERIXAFOR
10.05	ED50	0.09	nM	CHEMBL513863
10.05	ED50	0.09	nM	CHEMBL468733
10.05	ED50	0.09	nM	CHEMBL453720
10.00	IC50	0.1	nM	CHEMBL494191
10.00	Kd	0.1	nM	VERCIRNON
9.89	IC50	0.13	nM	CHEMBL3770912
9.82	IC50	0.15	nM	CHEMBL230933
9.70	IC50	0.2	nM	CHEMBL3233186
9.70	IC50	0.2	nM	CHEMBL3233188
9.70	IC50	0.2	nM	CHEMBL258205
9.70	IC50	0.2	nM	CHEMBL494191
9.70	ED50	0.2	nM	CHEMBL506023
9.70	IC50	0.2	nM	CHEMBL502247
9.64	Kd	0.23	nM	CHEMBL2426341
9.64	IC50	0.23	nM	CHEMBL437359
9.62	IC50	0.24	nM	CHEMBL3577945
9.60	IC50	0.25	nM	CHEMBL3263286
9.60	IC50	0.25	nM	CHEMBL41275
9.52	IC50	0.3	nM	CHEMBL522688
9.52	IC50	0.3	nM	CHEMBL4764460
9.52	IC50	0.3	nM	CHEMBL497202
9.52	IC50	0.3	nM	CHEMBL1090893
9.49	IC50	0.32	nM	CHEMBL231039
9.47	IC50	0.34	nM	CHEMBL3233186
9.43	IC50	0.37	nM	CHEMBL497202
9.42	Ki	0.3802	nM	CHEMBL4544504
9.40	IC50	0.4	nM	CHEMBL3577948
9.40	Ki	0.4	nM	CHEMBL4483373
9.40	Ki	0.4	nM	CHEMBL4544504
9.40	IC50	0.4	nM	BMS-741672
9.40	IC50	0.4	nM	CHEMBL1092678
9.37	IC50	0.43	nM	CHEMBL230281
9.37	IC50	0.4266	nM	CHEMBL230281
9.36	ED50	0.44	nM	CHEMBL512094
9.35	Ki	0.4467	nM	CHEMBL4483373
9.32	Kd	0.48	nM	MK-0812
9.30	IC50	0.5	nM	PF-4136309
9.30	IC50	0.5	nM	CHEMBL3233187
9.30	IC50	0.5	nM	CHEMBL1091605
9.30	IC50	0.5	nM	CHEMBL3577946
9.30	IC50	0.5	nM	CHEMBL271828
9.30	ED50	0.5	nM	CHEMBL444736
9.30	ED50	0.5	nM	CHEMBL526704

PubChem BioAssay actives

2693 with measured affinity, of 3742 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
dimethyl-[[4-[[3-(4-methylphenyl)-8,9-dihydro-7H-benzo[7]annulene-6-carbonyl]amino]phenyl]methyl]-(oxan-4-yl)azanium chloride	381444: Displacement of [125I]MCP1 from CCR2/CXCR4 expressed in CHOK1 cells	ic50	<0.0001	uM
Plerixafor	381445: Displacement of [125I]SDF1alpha from CCR2/CXCR4 expressed in CHOK1 cells	ic50	<0.0001	uM
4-tert-butyl-N-[4-chloro-2-(1-oxidopyridin-1-ium-4-carbonyl)phenyl]benzenesulfonamide	1957043: Binding affinity to CCR2 (unknown origin) assessed as dissociation constant	kd	0.0001	uM
trans-(1S,3R)-N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-3-[(1S,3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]-1-propan-2-ylcyclopentane-1-carboxamide	290742: Inhibition of chemotaxis in human MCP1 monocytes	ic50	0.0001	uM
trans-(1S,3R)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-[(3-methyloxan-4-yl)amino]-1-propan-2-ylcyclopentane-1-carboxamide	418627: Antagonist activity at human CCR2 receptor expressed in CHO cells by chemotaxis assay	ic50	0.0001	uM
N-[2-[[(3S,4S)-1-[4-(1,3-benzodioxol-5-yl)-4-hydroxycyclohexyl]-4-ethoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	771594: Displacement of [3H]INCB3344 from human CCR2 receptor expressed in human U2OS cell membranes assessed as association and dissociation of radioligand	kd	0.0002	uM
N-[2-[[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-[(4-methylsulfanylphenyl)sulfonylmethyl]cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	375876: Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced chemotaxis	ic50	0.0002	uM
(E)-3-(3,4-dichlorophenyl)-1-[4-[2-hydroxy-1-[4-(1H-indol-3-yl)piperidin-1-yl]ethyl]piperidin-1-yl]prop-2-en-1-one	331219: Binding affinity at human CCR2 receptor	ic50	0.0002	uM
trans-(1S,3R)-1-cyclopropyl-N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-3-[(1S,3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]cyclopentane-1-carboxamide	290742: Inhibition of chemotaxis in human MCP1 monocytes	ic50	0.0002	uM
(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-propylcyclohexyl]-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-2-one	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0002	uM
N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-(propan-2-ylsulfonylmethyl)cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0002	uM
N-[(3S)-1-[(1S,2R,4R)-2-(tert-butylsulfonylmethyl)-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0002	uM
N-[2-[[(1S,2R,4R)-4-(dimethylamino)-2-[(4-methylsulfanylphenyl)sulfonylmethyl]cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	375875: Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced calcium flux by fluorescence-imaging plate reader assay	ic50	0.0003	uM
trans-(1R,3R)-N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-1-(2-methylpropyl)-3-[(1S,3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]cyclopentane-1-carboxamide	290742: Inhibition of chemotaxis in human MCP1 monocytes	ic50	0.0003	uM
trans-(1S,3R)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-[(3-ethyloxan-4-yl)amino]-1-propan-2-ylcyclopentane-1-carboxamide	418627: Antagonist activity at human CCR2 receptor expressed in CHO cells by chemotaxis assay	ic50	0.0003	uM
N-[(3S)-1-[(1S,2R,4R)-2-(benzenesulfonylmethyl)-4-[ethyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	474888: Displacement of [125I]-MCP1 from CCR2 in human THP1 cells after 30 mins	ic50	0.0003	uM
3-[1-[(3aS,5S,6aR)-3a-[6-(trifluoromethyl)-2,4-dihydro-1,3-benzoxazine-3-carbonyl]-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-5-yl]piperidin-4-yl]-N-methylbenzamide	1138982: Displacement of labeled MCP-1 from human CCR2 expressed in THP1 cells	ic50	0.0003	uM
N-[(3S)-1-[(1S,2R,4R)-2-acetamido-4-(tert-butylamino)cyclohexyl]-2-oxopyrrolidin-3-yl]-6-tert-butylpyridine-2-carboxamide	1710272: Antagonist activity at CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 30 mins by calcein-AM dye based fluorescence assay	ic50	0.0003	uM
N-[(1R,2S,5R)-5-[methyl(propan-2-yl)amino]-2-[(3S)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]methanesulfonamide	1542565: Displacement of [125I]MCP1 from CCR2 in human PBMC measured after 30 mins	ic50	0.0004	uM
2-amino-6-[(3-bromo-4-chlorophenyl)methyl]-5-propan-2-yl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0004	uM
(3S)-1-[(1S,2S,4R)-4-[methyl(propan-2-yl)amino]-2-propan-2-ylcyclohexyl]-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-2-one	1226281: Inhibition of [125I]hMCP1 binding to CCR2 in human PBMC incubated for 30 mins at room temperature	ic50	0.0004	uM
(2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(methylcarbamoylamino)-1,3-thiazol-4-yl]-4-(4-phenylpiperidin-1-yl)butanamide	289625: Displacement of [125I]MCP1 from human CCR2 expressed in monocytes	ic50	0.0004	uM
N-[(3S)-1-[(1S,2R,4R)-2-[(4-methylphenyl)sulfonylmethyl]-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	474888: Displacement of [125I]-MCP1 from CCR2 in human THP1 cells after 30 mins	ic50	0.0004	uM
2-amino-5-cyclopropyl-6-[(3,4-dichlorophenyl)methyl]-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0004	uM
N-[2-[[(2S,3S)-1-(2,2-dimethylpropylamino)-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-2-(propan-2-ylcarbamoylamino)-5-(trifluoromethyl)benzamide	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0004	uM
N-[2-[[(2S,3S)-3-hydroxy-1-(2-methylpropylamino)hexan-2-yl]amino]-2-oxoethyl]-2-(propan-2-ylcarbamoylamino)-5-(trifluoromethyl)benzamide	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0004	uM
[(1S,3R)-3-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	1200137: Displacement of 0.1 nM [125I]CCL2 from human CCR2 expressing human U2OS cell membrane by scintillation spectrometry	kd	0.0005	uM
N-[2-[(3S)-3-[[4-hydroxy-4-(5-pyrimidin-2-yl-2-pyridinyl)cyclohexyl]amino]pyrrolidin-1-yl]-2-oxoethyl]-3-(trifluoromethyl)benzamide	662875: Inhibition of CCR2-mediated Erk phosphorylation	ic50	0.0005	uM
2-(cyclohexanecarbonylamino)-N-[2-oxo-2-[[(1S,2R)-2-[(4-sulfamoylbenzoyl)amino]cyclohexyl]amino]ethyl]-5-(trifluoromethyl)benzamide	315320: Antagonist activity at human CCR2 in PBMCs assessed as inhibition of chemotaxis	ic50	0.0005	uM
N-[(3S)-1-[(1S,2R,4R)-2-(benzenesulfonylmethyl)-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0005	uM
(3S)-1-[(1S,2R,4R)-2-ethyl-4-[methyl(propan-2-yl)amino]cyclohexyl]-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-2-one	1226281: Inhibition of [125I]hMCP1 binding to CCR2 in human PBMC incubated for 30 mins at room temperature	ic50	0.0005	uM
3-tert-butyl-N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-(propan-2-ylsulfonylmethyl)cyclohexyl]-2-oxopyrrolidin-3-yl]benzamide	1129742: Displacement of [125I]-labeled human MCP1 from CCR2 in human PBMC	ic50	0.0005	uM
(E)-3-(3,5-difluorophenyl)-1-[4-[2-hydroxy-1-[4-(1H-indol-3-yl)piperidin-1-yl]ethyl]piperidin-1-yl]prop-2-en-1-one	331219: Binding affinity at human CCR2 receptor	ic50	0.0006	uM
N-[3-[1-[1-[1-[(E)-3-(3,4-dichlorophenyl)prop-2-enoyl]piperidin-4-yl]-2-hydroxyethyl]piperidin-4-yl]-1H-indol-5-yl]methanesulfonamide	331219: Binding affinity at human CCR2 receptor	ic50	0.0006	uM
2-amino-6-[(3,4-dichlorophenyl)methyl]-5-propan-2-yl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0006	uM
2-[[4-[4-chloro-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]phenoxy]benzoyl]amino]ethyl thiocyanate	1732352: Displacement of [3H]-CCR2-RA-(R) from human CCR2b expressed in human U2OS cell membranes pre-incubated for 4 hrs before radio ligand addition and measured after 20 mins by scintillation counting method	ki	0.0006	uM
N-[(1R,2S,5R)-5-(tert-butylamino)-2-[(3S)-3-[(6-tert-butylpyrido[3,2-d]pyrimidin-4-yl)amino]-2-oxopyrrolidin-1-yl]cyclohexyl]acetamide	1710272: Antagonist activity at CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 30 mins by calcein-AM dye based fluorescence assay	ic50	0.0006	uM
2-(2-acetamido-1,3-thiazol-4-yl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-[(3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]butanamide	289650: Inhibition of MCP1-stimulated chemotaxis in monocytes transfected with human CCR2	ic50	0.0006	uM
2-(ethylcarbamoylamino)-N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-propylcyclohexyl]-2-oxopyrrolidin-3-yl]-5-(trifluoromethyl)benzamide	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0006	uM
N-[(3S)-1-[(1S,2R,4R)-2-(ethylsulfonylmethyl)-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0006	uM
[6-(3,4-dichloroanilino)-2-(fluoromethyl)-5-methylpyrimidin-4-yl]-[4-[[(3S,4S)-3-methoxyoxan-4-yl]amino]piperidin-1-yl]methanone	734806: Displacement of [125I]MCP1 from CCR2 in human THP1 cell membranes after 8 hrs by scintillation counting analysis	ki	0.0006	uM
N-[2-[[(1S,2R,4R)-4-(diethylamino)-2-[(4-methylsulfanylphenyl)sulfonylmethyl]cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	375875: Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced calcium flux by fluorescence-imaging plate reader assay	ic50	0.0007	uM
(2S)-2-(2-acetamido-1,3-thiazol-4-yl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(4-phenylpiperidin-1-yl)butanamide	289650: Inhibition of MCP1-stimulated chemotaxis in monocytes transfected with human CCR2	ic50	0.0007	uM
N-[(1R,2S,5R)-5-[methyl(propan-2-yl)amino]-2-[(3S)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide	1542579: Inhibition of CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 10 mins by calcein-AM dye based fluorescence assay	ic50	0.0007	uM
2-(2-acetamido-1,3-thiazol-4-yl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-spiro[indene-1,4’-piperidine]-1’-ylbutanamide	289650: Inhibition of MCP1-stimulated chemotaxis in monocytes transfected with human CCR2	ic50	0.0007	uM
6-tert-butyl-N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-(methylsulfonylmethyl)cyclohexyl]-2-oxopyrrolidin-3-yl]pyridine-2-carboxamide	1129742: Displacement of [125I]-labeled human MCP1 from CCR2 in human PBMC	ic50	0.0007	uM
2-amino-6-[(3-bromophenyl)methyl]-5-cyclopropyl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0008	uM
N-[(1R,2S,5R)-5-(tert-butylamino)-2-[(3S)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide	1710272: Antagonist activity at CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 30 mins by calcein-AM dye based fluorescence assay	ic50	0.0008	uM
2-amino-N-[2-[[(3R)-1-[(2,4-dimethylphenyl)methyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide	325951: Antagonist activity at human CCR2 in THP1 cells assessed as inhibition of MCP1-induced chemotaxis	ic50	0.0008	uM
(2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(methylcarbamoylamino)-1,3-thiazol-4-yl]-4-spiro[indene-1,4’-piperidine]-1’-ylbutanamide	289625: Displacement of [125I]MCP1 from human CCR2 expressed in monocytes	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression, decreases reaction, affects expression, decreases expression	4
Arsenic	affects expression, affects methylation, affects cotreatment, decreases expression	3
Dinitrochlorobenzene	decreases expression, increases expression	3
Simvastatin	affects binding, decreases activity, decreases expression, decreases reaction, increases expression	3
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression, increases expression	2
Lipopolysaccharides	decreases expression, increases expression, affects response to substance, affects cotreatment, decreases reaction	2
Piperidines	affects binding, decreases activity, decreases reaction	2
Cyclosporine	affects cotreatment, increases expression	2
Antirheumatic Agents	decreases expression	2
Zinc Sulfate	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
captax	increases expression	1
trichostatin A	decreases reaction, affects expression	1
proanthocyanidin	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
ammonium hexachloroplatinate	decreases expression	1
4-phenylenediamine	decreases expression	1
aflatoxin B2	increases methylation	1
2,2’,3’,4,4’,5-hexachlorobiphenyl	affects expression	1
nickel sulfate	decreases expression	1
3-chlorophenol	increases expression	1
sodium chlorate	decreases sulfation, decreases reaction, increases activity	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, decreases expression, affects response to substance	1
nefazodone	increases expression, affects cotreatment	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	decreases expression, decreases reaction	1
SB 203580	decreases reaction, increases expression	1
U 0126	decreases reaction, increases expression	1
1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine	increases expression	1

ChEMBL screening assays

426 unique, capped per target: 277 binding, 149 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001496	Binding	Displacement of [125I]MCP1 from CCR2 in human PBMC by millipore filter plate assay	Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. — *Bioorg Med Chem Lett*
CHEMBL1001497	Functional	Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced calcium flux by fluorescence-imaging plate reader assay	Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D95	HOS-CD4-CCR2b	Cancer cell line	Female
CVCL_1E07	GHOST(3).CCR2b	Cancer cell line	Female
CVCL_B9WZ	Abcam THP-1 CCR2 KO	Cancer cell line	Male
CVCL_E4JY	HEK293 CCR2 isoform B	Transformed cell line	Female
CVCL_KW56	PathHunter CHO-K1 CCR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ38	PathHunter HEK 293 CCR2 beta-arrestin	Transformed cell line	Female
CVCL_KZ94	PathHunter U2OS CCR2 Total GPCR Internalization	Cancer cell line	Female
CVCL_RQ09	ValiScreen human CCR2b	Spontaneously immortalized cell line	Female
CVCL_X628	U87.CD4.CCR2	Cancer cell line	Male
CVCL_ZJ99	Tango CCR2-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CCR2 across ~30M SureChEMBL compounds — explore on Sugi Predict.