CCL2

Summary

CCL2 (C-C motif chemokine ligand 2, HGNC:10618) is a protein-coding gene on chromosome 17q12, encoding C-C motif chemokine 2 (P13500). Acts as a ligand for C-C chemokine receptor CCR2.

This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection.

Source: NCBI Gene 6347 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neural tube defects, susceptibility to (No Known Disease Relationship, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 14 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002982

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10618
Approved symbol	CCL2
Name	C-C motif chemokine ligand 2
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	MCP1, MCP-1, MCAF, SMC-CF, GDCF-2, HC11, MGC9434
Ensembl gene	ENSG00000108691
Ensembl biotype	protein_coding
OMIM	158105
Entrez	6347

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000225831, ENST00000580907, ENST00000624362

RefSeq mRNA: 1 — MANE Select: NM_002982 NM_002982

CCDS: CCDS11277

Canonical transcript exons

ENST00000225831 — 3 exons

Exon	Start	End
ENSE00000713589	34256222	34256339
ENSE00001161442	34256722	34257203
ENSE00003965470	34255285	34255425

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 823.1161 / max 273834.0967, expressed in 1344 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160295	822.9960	1344
160296	0.1053	39
160297	0.0148	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	99.78	gold quality
gall bladder	UBERON:0002110	99.17	gold quality
islet of Langerhans	UBERON:0000006	98.52	gold quality
metanephros cortex	UBERON:0010533	98.49	gold quality
mucosa of stomach	UBERON:0001199	98.35	gold quality
type B pancreatic cell	CL:0000169	98.22	gold quality
rectum	UBERON:0001052	97.90	gold quality
left uterine tube	UBERON:0001303	97.83	gold quality
smooth muscle tissue	UBERON:0001135	97.67	gold quality
saphenous vein	UBERON:0007318	97.05	gold quality
colonic epithelium	UBERON:0000397	96.90	gold quality
right atrium auricular region	UBERON:0006631	96.85	gold quality
heart right ventricle	UBERON:0002080	96.83	gold quality
omental fat pad	UBERON:0010414	96.63	gold quality
peritoneum	UBERON:0002358	96.61	gold quality
right coronary artery	UBERON:0001625	96.59	gold quality
left adrenal gland	UBERON:0001234	96.58	gold quality
left adrenal gland cortex	UBERON:0035825	96.57	gold quality
cardiac atrium	UBERON:0002081	96.54	gold quality
vermiform appendix	UBERON:0001154	96.45	gold quality
cartilage tissue	UBERON:0002418	96.42	gold quality
left coronary artery	UBERON:0001626	96.07	gold quality
ascending aorta	UBERON:0001496	96.05	gold quality
thoracic aorta	UBERON:0001515	96.02	gold quality
coronary artery	UBERON:0001621	95.92	gold quality
adrenal cortex	UBERON:0001235	95.86	gold quality
upper lobe of left lung	UBERON:0008952	95.53	gold quality
caecum	UBERON:0001153	95.49	gold quality
pancreas	UBERON:0001264	95.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.29	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	14010.37
E-MTAB-10855	yes	7526.27
E-MTAB-9067	yes	7350.99
E-CURD-46	yes	24.18
E-GEOD-81547	yes	21.90
E-GEOD-83139	yes	11.42
E-GEOD-130148	yes	9.92
E-MTAB-10553	yes	7.15
E-CURD-7	no	5214.93
E-ENAD-21	no	4722.83
E-MTAB-10662	no	2376.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CSF1	Activation
ITGAX	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, APEX1, APP, ATF2, ATF3, ATF4, BCL6, BMAL1, CD74, CEBPA, CEBPB, CEBPD, CEBPG, CREB1, CRP, CSF1, CTNNB1, DDIT3, EGR1, EGR2, ESR1, ESR2, ETS1, ETV4, ETV6, FLI1, FOS, FOSL1, FOXC1, FOXO1, H4C2, HDAC2, HIF1A, HR, IFNG, IL34, IRF1, IRF3, IRF5

miRNA regulators (miRDB)

46 targeting CCL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-2110	99.96	66.68	1930
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4318	99.38	66.94	1505

Literature-anchored findings (GeneRIF, showing 40)

• Differential production of RANTES and MCP-1 in synovial fluid from the inflamed human knee. (PMID:11750041)
• These studies demonstrate that PEIPC and PECPC isomers are potent activators of endothelial cells increasing synthesis of IL-8 and MCP-1. (PMID:11751881)
• Contact hypersensitivity are significantly enhanced in the hMCP-1 Tgm, which appears to result from a constitutive activation of LC with the systemic presence of large amount of hMCP-1. (PMID:11776402)
• overexpression in mesangial cells by advanced glycation end products (PMID:11912219)
• Inflammatory cytokines mediate C-C (monocyte chemotactic protein 1) and C-X-C (interleukin 8) chemokine expression in human pleural fibroblasts. (PMID:11989790)
• Increased expression in atherectomy specimens from patients with restenosis after percutaneous transluminal coronary angioplasty (PMID:11999660)
• Monocyte chemotactic protein-1 and macrophage migration inhibitory factor production by peritoneal macrophages may contribute to paracrine and autocrine activation and to macrophage accumulation in peritoneal cavity of women with endometriosis. (PMID:12009356)
• LPS-stimulated production of MCP-1 was significantly less in infected patients. Serum concentrations of both mediators were higher in infected patients and the highest concentrations of MCP-1 were in patients who died (PMID:12022754)
• Monocyte chemoattractant protein-1 induces proliferation and interleukin-6 production in smooth muscle cells by differential activation of nuclear factor-kappa B and activator protein-1. (PMID:12067898)
• expression of MCP in aiway epithelial cells after injury enhances cell migration and proliferation (PMID:12078856)
• Fluid shear stress induces the secretion of monocyte chemoattractant protein-1 in cultured human umbilical vein endothelial cells (PMID:12082252)
• plasmin induction of MCP-1 in human monocytes (PMID:12093796)
• Simvastatin reduces expression of the proinflammatory cytokine monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. (PMID:12117737)
• MCP1 is upregulatied in Peyronie’s disease (PMID:12127997)
• Induction of the gene encoding macrophage chemoattractant protein 1 by Orientia tsutsugamushi in human endothelial cells involves activation of transcription factor activator protein 1. (PMID:12183528)
• enhances the migration of bone marrow stromal cells (PMID:12186702)
• upstream signaling events in platelet-induced NF-kappa B activation that induce secretion of NF-kappa B-regulated chemokine MCP-1. (PMID:12195705)
• Toxoplasma gondii tachyzoites induced MCP-1 expression and secretion in infected fibroblasts (PMID:12204371)
• Monocyte chemotactic protein-1 directly induces human vascular smooth muscle proliferation. (PMID:12234797)
• Recipients of renal transplants homozygous for the -2518 G mutation of the MCP-1 gene are at risk for premature kidney graft failure. (PMID:12239249)
• may be a marker of early development of nephropathy in IDDM (PMID:12351486)
• first report of monocyte chemotactic protein-1 expression in mesothelial cells induced by oxidized LDL, and provides direct evidence of inflammatory action of peritoneal fluid of women with endometriosis (PMID:12372466)
• influence of genetic variation in MCP-1 on HIV-1 pathogenesis in large cohorts of HIV-1-infected adults and children (PMID:12374865)
• Circulating ICAM-1, IL-8, and MCP-1 in untreated obstructive sleep apnea were significantly greater than in controls. nCPAP therapy could reduce OSAS-induced hypoxia and generation of inflammatory mediators. (PMID:12391099)
• MCP-1 modulates the differentiation of monocytes into dendritic cells and may thereby inhibit Th1 cell development. (PMID:12391196)
• We used specific pharmacologic inhibitors to identify the signalling molecules which lead to interleukin (IL)-8 and MCP-1 production in human monocytes in response to M. tuberculosis infection (PMID:12393171)
• MCP-1 may play a role in progression of human esophageal carcinoma through its role in angiogenesis (PMID:12397639)
• 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)
• homozygosity for G at -2518 in the MCP-1 gene might be a candidate for the genetic marker of Carpal-tunnel syndrome development in Japanese hemodialysis patients (PMID:12408680)
• some heat-stable component of P. gingivalis, including LPS, may be responsible for the induction of IL-8 and MCP-1 in HUVECs by a CD14-dependent mechanism (PMID:12410798)
• The polymorphisms of the MCP-1 and MIP-1A genes do not play a substantial role in genetic predisposition for sarcoidosis or in clinical manifestations of sarcoidosis in this Japanese population. (PMID:12413001)
• mechanism of gamma-Herpesvirus MCP-1 sequestration (PMID:12419245)
• induction of MCP-1 by Porphyromonas gingivalis in endothelial cells could enhance atherosclerosis progression by contributing to the recruitment of monocytes (PMID:12443832)
• A genetic polymorphism in the 5’ flanking region of the MCP-1 gene is associated with nephritis in lupus through modulating MCP-1 expression. (PMID:12460032)
• Escherichia coli activates kidney proximal tubular cells to generate MCP-1 that promotes migration of monocytes in vitro. (PMID:12470469)
• IL-10 has two contrasting actions on MCP-1 production of monocytes/macrophages, between the resting and activated conditions. (PMID:12488502)
• results suggest that monocyte chemoattractant protein-1 is produced in renal tubular cells and released into urine in proportion to the degree of proteinuria (albuminuria), and its increased expression in renal tubuli contributes to renal tubular damage (PMID:12505750)
• Myxomas with both high tumor and high stromal MCP-1 expression had a higher macrophage count than other myxomas. In cardiac myxoma, MCP-1 and thymidine phosphorylase may be important angiogenic signals accompanying growth. (PMID:12520153)
• results revealed that Porphyromonas gingivalis induces the expression of IL-8 and MCP-1 mRNAs in vascular endothelial cells, but bacterial proteases degrade both chemokines (PMID:12520365)
• The ability of activated protein C to upregulate the production of MCP-1 is most likely by increasing the stability of MCP-1-mRNA rather than by transcriptional activation via NF-KB (PMID:12540965)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcl32b.1	ENSDARG00000071499
mus_musculus	Ccl2	ENSMUSG00000035385
rattus_norvegicus	Ccl2	ENSRNOG00000007159

Paralogs (26): CX3CL1 (ENSG00000006210), CCL26 (ENSG00000006606), CCL22 (ENSG00000102962), CCL17 (ENSG00000102970), CCL24 (ENSG00000106178), CCL7 (ENSG00000108688), CCL8 (ENSG00000108700), CCL1 (ENSG00000108702), CCL20 (ENSG00000115009), CCL25 (ENSG00000131142), CCL21 (ENSG00000137077), XCL1 (ENSG00000143184), XCL2 (ENSG00000143185), CCL11 (ENSG00000172156), CCL19 (ENSG00000172724), CCL13 (ENSG00000181374), CCL5 (ENSG00000271503), CCL23 (ENSG00000274736), CCL16 (ENSG00000275152), CCL4 (ENSG00000275302), CCL18 (ENSG00000275385), CCL15 (ENSG00000275718), CCL4L2 (ENSG00000276070), CCL3L3 (ENSG00000276085), CCL14 (ENSG00000276409), CCL3 (ENSG00000277632)

Protein

Protein identifiers

C-C motif chemokine 2 — P13500 (reviewed: P13500)

Alternative names: HC11, Monocyte chemoattractant protein 1, Monocyte chemotactic and activating factor, Monocyte chemotactic protein 1, Monocyte secretory protein JE, Small-inducible cytokine A2

All UniProt accessions (2): P13500, J3KRT7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a ligand for C-C chemokine receptor CCR2. Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions. Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis.

Subunit / interactions. Monomer or homodimer; in equilibrium. Is tethered on endothelial cells by glycosaminoglycan (GAG) side chains of proteoglycans. Interacts with TNFAIP6 (via Link domain).

Subcellular location. Secreted.

Tissue specificity. Expressed in the seminal plasma, endometrial fluid and follicular fluid (at protein level). Expressed in monocytes.

Post-translational modifications. Processing at the N-terminus can regulate receptor and target cell selectivity. Deletion of the N-terminal residue converts it from an activator of basophil to an eosinophil chemoattractant. N-Glycosylated.

Induction. Up-regulated upon hypertonic conditions. In pancreatic islets, secretion is stimulated by IL1B. Up-regulated by coagulation factor Xa (F10) in PAR-1 (F2R)-dependent manner in cardiac fibroblasts and endothelial cells. Up-regulated by thrombin (F2) in endothelial cells.

Polymorphism. Genetic variations in CCL2 determine Mycobacterium tuberculosis susceptibility [MIM:607948].

Similarity. Belongs to the intercrine beta (chemokine CC) family.

RefSeq proteins (1): NP_002973* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000827	Chemokine_CC_CS	Conserved_site
IPR001811	Chemokine_IL8-like_dom	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (48 total): mutagenesis site 23, site 10, strand 6, helix 3, disulfide bond 2, signal peptide 1, chain 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
7SO0	X-RAY DIFFRACTION	1.74
1DOK	X-RAY DIFFRACTION	1.85
3IFD	X-RAY DIFFRACTION	1.9
4R8I	X-RAY DIFFRACTION	2.05
1DOL	X-RAY DIFFRACTION	2.4
2NZ1	X-RAY DIFFRACTION	2.5
2BDN	X-RAY DIFFRACTION	2.53
4ZK9	X-RAY DIFFRACTION	2.6
1ML0	X-RAY DIFFRACTION	2.8
4DN4	X-RAY DIFFRACTION	2.8
7XA3	ELECTRON MICROSCOPY	2.9
8FJ0	X-RAY DIFFRACTION	2.91
1DOM	SOLUTION NMR
1DON	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13500-F1	87.51	0.63

Antibody-complex structures (SAbDab): 3 — 2BDN, 4DN4, 7XA3

Functional residue map

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

Catalytic / active sites (10): 81 (involved in gag binding); 89 (involved in gag binding); 31 (involved in dimerization); 36 (involved in dimerization, receptor binding and signaling); 41 (involved in gag binding); 42 (involved in gag binding); 47 (involved in gag binding and receptor binding); 58 (involved in dimerization); 61 (involved in dimerization); 72 (involved in gag binding and receptor binding)

Post-translational modifications (1): 24

Disulfide bonds (2): 34–59, 35–75

Glycosylation sites (1): 37

Mutagenesis-validated functional residues (23):

Position	Phenotype
24–91	83% reduction in activity.
24–85	90% reduction in activity.
24	loss of activity.
25–31	loss of signaling.
26	reduction in activity.
28	slight reduction in activity.
29	50% reduction in activity.
31	loss of dimerization; slight reduction of activity.
32	slight reduction in activity.
32	slight reduction in affinity.
33	slight reduction in activity.
33	slight reduction in affinity.
36	loss of activity.
41–42	abolishes binding to link domain of tnfaip6.
47	95% reduction in activity; strong reduction of receptor binding.
50	40% reduction in activity.
51	loss of activity.
53	loss of activity.
79	no effect on heparin binding.
81	strongly reduces heparin binding.
89	strongly reduces heparin binding.
91	90% reduction in activity.
95–99	no effect on heparin binding.

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9818026	NFE2L2 regulating inflammation associated genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-2262752	Cellular responses to stress
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-381042	PERK regulates gene expression
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-449147	Signaling by Interleukins
R-HSA-500792	GPCR ligand binding
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress
R-HSA-9755511	KEAP1-NFE2L2 pathway
R-HSA-9759194	Nuclear events mediated by NFE2L2

MSigDB gene sets: 753 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, MODULE_52, MODULE_92, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, MCLACHLAN_DENTAL_CARIES_UP

GO Biological Process (50): angiogenesis (GO:0001525), monocyte chemotaxis (GO:0002548), protein phosphorylation (GO:0006468), chemotaxis (GO:0006935), inflammatory response (GO:0006954), humoral immune response (GO:0006959), cytoskeleton organization (GO:0007010), cell adhesion (GO:0007155), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), regulation of cell shape (GO:0008360), response to bacterium (GO:0009617), animal organ morphogenesis (GO:0009887), positive regulation of gene expression (GO:0010628), positive regulation of macrophage chemotaxis (GO:0010759), viral genome replication (GO:0019079), cytokine-mediated signaling pathway (GO:0019221), sensory perception of pain (GO:0019233), cellular homeostasis (GO:0019725), positive regulation of cell migration (GO:0030335), negative regulation of glial cell apoptotic process (GO:0034351), helper T cell extravasation (GO:0035684), chemokine (C-C motif) ligand 2 signaling pathway (GO:0038148), negative regulation of neuron apoptotic process (GO:0043524), astrocyte cell migration (GO:0043615), cellular response to fibroblast growth factor stimulus (GO:0044344), eosinophil chemotaxis (GO:0048245), macrophage chemotaxis (GO:0048246), positive regulation of T cell activation (GO:0050870), positive regulation of synaptic transmission, glutamatergic (GO:0051968), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098), cellular response to lipopolysaccharide (GO:0071222), cellular response to type II interferon (GO:0071346), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356)

GO Molecular Function (9): protein kinase activity (GO:0004672), signaling receptor binding (GO:0005102), chemokine activity (GO:0008009), CCR2 chemokine receptor binding (GO:0031727), chemoattractant activity (GO:0042056), chemokine receptor binding (GO:0042379), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Signaling by Interleukins	2
Cellular responses to stress	2
Peptide ligand-binding receptors	1
PERK regulates gene expression	1
Nuclear events mediated by NFE2L2	1
Immune System	1
Cellular responses to stimuli	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Unfolded Protein Response (UPR)	1
Cytokine Signaling in Immune system	1
Signaling by GPCR	1
Cellular response to chemical stress	1
KEAP1-NFE2L2 pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
signal transduction	2
regulation of biological quality	2
chemokine receptor binding	2
receptor ligand activity	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
phosphorylation	1
protein modification process	1
response to chemical	1
taxis	1
defense response	1
immune response	1
organelle organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway	1
cell surface receptor signaling pathway via STAT	1
regulation of cell morphogenesis	1
response to other organism	1
anatomical structure morphogenesis	1
animal organ development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
viral process	1
viral life cycle	1
kinase activity	1

Protein interactions and networks

STRING

5672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL2	CCR2	P41597	999
CCL2	CCR5	P51681	998
CCL2	CCR1	P32246	997
CCL2	CX3CR1	P49238	996
CCL2	CXCR3	P49682	995
CCL2	CCR3	P51677	995
CCL2	CXCR2	P25025	994
CCL2	CXCR4	P30991	994
CCL2	ACKR1	Q16570	993
CCL2	CCRL2	O00421	990
CCL2	CCR6	P51684	990
CCL2	CXCR1	P25024	989
CCL2	ACKR2	O00590	972
CCL2	CCL20	P78556	962
CCL2	IL6	P05231	954

IntAct

35 interactions, top by confidence:

A	B	Type	Score
MET	SRC	psi-mi:“MI:0914”(association)	0.790
SRC	MET	psi-mi:“MI:0914”(association)	0.790
	CCL2	psi-mi:“MI:0407”(direct interaction)	0.680
CCL2	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL2	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
	CCL2	psi-mi:“MI:0915”(physical association)	0.560
CCL2	TMX2	psi-mi:“MI:0915”(physical association)	0.560
CCL2	RNF4	psi-mi:“MI:0915”(physical association)	0.560
GAMMAHV.M3	CCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCL15	CCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CCL8	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CXCL8	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CXCL9	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CXCL17	psi-mi:“MI:0407”(direct interaction)	0.440
CCL8	CCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CXCL13	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	CCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CCL4L1	psi-mi:“MI:0407”(direct interaction)	0.440
CTTN	CCL2	psi-mi:“MI:0915”(physical association)	0.400
PROM1	CCL2	psi-mi:“MI:0915”(physical association)	0.370
CCL2		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (42): ACKR1 (Reconstituted Complex), CCL2 (Two-hybrid), SLC16A2 (Two-hybrid), TMX2 (Two-hybrid), CCL2 (Reconstituted Complex), CCL2 (PCA), CCL2 (PCA), CCL2 (Reconstituted Complex), CCL2 (Reconstituted Complex), CCL11 (Reconstituted Complex), CCL5 (Reconstituted Complex), CCL8 (Reconstituted Complex), CXCL17 (Reconstituted Complex), PF4 (Reconstituted Complex), CXCL8 (Reconstituted Complex)

ESM2 similar proteins: F5HET8, O00626, O88430, O89093, P08317, P10889, P12850, P13500, P14095, P19874, P28291, P30348, P36925, P42830, P42831, P46653, P49873, P51671, P52203, P55774, P61274, P61275, P78556, P80075, P80098, P80221, P82943, Q03366, Q09141, Q16627, Q5RA36, Q62401, Q68AY9, Q68Y88, Q6W5C0, Q8HYP8, Q8HYP9, Q8I021, Q8MIT7, Q8SQB1

Diamond homologs: F5HET8, O00175, O00585, O00626, O55145, O88430, O97919, P10147, P10148, P10855, P13236, P13500, P13501, P14097, P14844, P16619, P27784, P28291, P28292, P30882, P42831, P46632, P47993, P49873, P50229, P50230, P50231, P51670, P51671, P52203, P55773, P55774, P61274, P61275, P78423, P80075, P80098, P80343, P82943, P97272

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
CCL2	“up-regulates activity”	CCR4	binding
HIF1A	“up-regulates quantity by expression”	CCL2	“transcriptional regulation”
CRP	“up-regulates quantity by expression”	CCL2	“transcriptional regulation”
NfKb-p65/p50	up-regulates	CCL2	“transcriptional regulation”
CCL2	“up-regulates activity”	CCR2	binding
NfKb-p65/p50	“up-regulates quantity by expression”	CCL2	“transcriptional regulation”
AP1	“up-regulates activity”	CCL2	“transcriptional regulation”
CCL2	up-regulates	Immune_response
CCL2	up-regulates	ARDS
CCL2	up-regulates	Inflammation
CCL2	up-regulates	M2_polarization
CCL2	up-regulates	Macrophage_activation
IFNAR	“up-regulates quantity by expression”	CCL2
Macrophage_activation	“up-regulates quantity”	CCL2
PRDM1	“down-regulates quantity by repression”	CCL2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Chemokine receptors bind chemokines	6	93.6×	3e-09
G alpha (i) signalling events	7	22.7×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	5	215.5×	1e-09
chemokine-mediated signaling pathway	9	171.6×	8e-17
antimicrobial humoral immune response mediated by antimicrobial peptide	9	85.8×	3e-14
neutrophil chemotaxis	5	84.0×	1e-07
chemotaxis	7	56.0×	1e-09
cell-cell signaling	6	24.6×	3e-06
inflammatory response	10	22.2×	2e-10
positive regulation of cell migration	6	21.8×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

167 predictions. Top by Δscore:

Variant	Effect	Δscore
17:34255421:GCCAG:G	donor_gain	1.0000
17:34255424:AGGT:A	donor_loss	1.0000
17:34256207:T:TA	acceptor_gain	1.0000
17:34256216:TTCCA:T	acceptor_loss	1.0000
17:34256217:TCCA:T	acceptor_loss	1.0000
17:34256220:A:AG	acceptor_gain	1.0000
17:34256221:G:GA	acceptor_loss	1.0000
17:34256221:G:GG	acceptor_gain	1.0000
17:34256221:GAT:G	acceptor_gain	1.0000
17:34256221:GATGC:G	acceptor_gain	1.0000
17:34256335:GTGAT:G	donor_gain	1.0000
17:34256337:GAT:G	donor_gain	1.0000
17:34256340:G:GG	donor_gain	1.0000
17:34256717:CACA:C	acceptor_loss	1.0000
17:34256718:ACAG:A	acceptor_loss	1.0000
17:34256719:CA:C	acceptor_loss	1.0000
17:34256720:A:AC	acceptor_loss	1.0000
17:34256720:A:AG	acceptor_gain	1.0000
17:34256721:G:GC	acceptor_gain	1.0000
17:34256721:GC:G	acceptor_gain	1.0000
17:34255427:T:A	donor_loss	0.9900
17:34256213:A:AG	acceptor_gain	0.9900
17:34256214:T:G	acceptor_gain	0.9900
17:34256220:AGAT:A	acceptor_gain	0.9900
17:34256221:GA:G	acceptor_gain	0.9900
17:34256221:GATG:G	acceptor_gain	0.9900
17:34256316:C:T	donor_gain	0.9900
17:34256336:TGAT:T	donor_gain	0.9900
17:34256336:TGATG:T	donor_loss	0.9900
17:34256337:GATG:G	donor_gain	0.9900

AlphaMissense

650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:34256773:G:C	W82C	0.988
17:34256773:G:T	W82C	0.988
17:34256724:T:C	F66S	0.985
17:34256771:T:A	W82R	0.976
17:34256771:T:C	W82R	0.976
17:34256724:T:G	F66C	0.965
17:34256320:T:C	C59R	0.963
17:34256320:T:A	C59S	0.962
17:34256321:G:C	C59S	0.962
17:34256750:T:A	C75S	0.952
17:34256751:G:C	C75S	0.952
17:34256775:T:A	V83D	0.947
17:34256288:T:A	L48H	0.946
17:34256753:G:C	A76P	0.945
17:34256750:T:C	C75R	0.937
17:34256332:G:C	A63P	0.936
17:34256336:T:A	V64E	0.935
17:34256783:T:C	S86P	0.932
17:34256751:G:A	C75Y	0.920
17:34256248:T:A	C35S	0.919
17:34256249:G:C	C35S	0.919
17:34256296:T:G	Y51D	0.915
17:34256752:T:G	C75W	0.914
17:34256774:G:C	V83L	0.912
17:34256245:T:C	C34R	0.910
17:34256754:C:A	A76D	0.909
17:34256245:T:A	C34S	0.907
17:34256246:G:C	C34S	0.907
17:34256248:T:C	C35R	0.907
17:34256322:T:G	C59W	0.897

dbSNP variants (sampled 300 via entrez): RS1000097225 (17:34254063 G>A,T), RS1003064174 (17:34254653 G>A), RS1003236569 (17:34257364 C>T), RS1003310038 (17:34257642 G>A,C), RS1004292278 (17:34254684 G>C), RS1006700403 (17:34256536 A>G), RS1006899508 (17:34253336 A>G), RS1007290590 (17:34254987 A>G), RS1007382697 (17:34253706 C>T), RS1007628411 (17:34257382 G>A), RS1007670288 (17:34254815 C>T), RS1007705149 (17:34257048 T>C), RS1007963222 (17:34255685 C>G), RS1009817530 (17:34257063 C>T), RS1010081898 (17:34255756 A>C)

Disease associations

OMIM: gene MIM:158105 | disease phenotypes: MIM:609423

GenCC curated gene-disease

Disease	Classification	Inheritance
neural tube defects, susceptibility to	No Known Disease Relationship	Autosomal dominant

Mondo (2): susceptibility to HIV infection (MONDO:0004951), neural tube defects, susceptibility to (MONDO:0020705)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000879_61	Crohn’s disease	2.000000e-13
GCST001438_14	Crohn’s disease	4.000000e-08
GCST001474_5	Hypothyroidism	7.000000e-06
GCST001725_28	Inflammatory bowel disease	1.000000e-26
GCST003854_13	Gut microbiota (functional units)	5.000000e-07
GCST003854_15	Gut microbiota (functional units)	6.000000e-07
GCST004131_81	Inflammatory bowel disease	1.000000e-12
GCST004132_101	Crohn’s disease	2.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1649052 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,544 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL38380	FASUDIL	3	11,953
CHEMBL4078100	AZD-5153	1	591

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2857657	Efficacy	3	risperidone	Schizophrenia
rs4586	Efficacy	3	risperidone	Schizophrenia
rs4795893	Efficacy	3	risperidone	Schizophrenia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4586	CCL2	3	4.12	1	risperidone
rs2857657	CCL2	3	3.00	1	risperidone
rs4795893	CCL2	3	4.12	1	risperidone

ChEMBL bioactivities

68 potent at pChembl≥5 of 70 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	IC50	0.03981	nM	CHEMBL5426022
9.60	IC50	0.2512	nM	CHEMBL5422047
8.50	IC50	3.162	nM	AZD-5153
8.30	IC50	5.012	nM	CHEMBL5426022
8.20	IC50	6.31	nM	CHEMBL5433432
8.20	IC50	6.31	nM	CHEMBL1957266
8.10	IC50	7.943	nM	CHEMBL4438171
7.90	IC50	12.59	nM	CHEMBL5403564
7.80	IC50	15.85	nM	CHEMBL5220494
7.80	IC50	15.85	nM	AZD-5153
7.70	IC50	19.95	nM	GSK789
7.70	IC50	19.95	nM	CHEMBL5219991
7.60	IC50	25.12	nM	CHEMBL5218813
7.60	IC50	25.12	nM	CHEMBL4438171
7.50	IC50	31.62	nM	GSK046
7.50	IC50	31.62	nM	CHEMBL5220128
7.50	IC50	31.62	nM	CHEMBL5219919
7.40	IC50	39.81	nM	CHEMBL5218822
7.40	IC50	39.81	nM	CHEMBL5218726
7.40	IC50	39.81	nM	CHEMBL5218909
7.40	IC50	39.81	nM	CHEMBL5219602
7.40	IC50	39.81	nM	CHEMBL5219538
7.40	IC50	39.81	nM	CHEMBL2017291
7.40	IC50	39.81	nM	GSK778
7.30	IC50	50.12	nM	GSK973
7.30	IC50	50.12	nM	CHEMBL5221069
7.30	IC50	50.12	nM	CHEMBL5218817
7.30	IC50	50.12	nM	CHEMBL5426762
7.30	IC50	50.12	nM	CHEMBL5220623
7.20	IC50	63.1	nM	GSK620
7.10	IC50	79.43	nM	CHEMBL5408181
6.90	IC50	125.9	nM	CHEMBL5219194
6.90	IC50	125.9	nM	CHEMBL5422047
6.80	IC50	158.5	nM	CHEMBL5219077
6.80	IC50	158.5	nM	GSK778
6.70	IC50	199.5	nM	CHEMBL5195288
6.70	IC50	199.5	nM	CHEMBL2017291
6.70	IC50	199.5	nM	CHEMBL4519518
6.60	IC50	251.2	nM	CHEMBL5190509
6.50	IC50	316.2	nM	GSK046
6.40	IC50	398.1	nM	CHEMBL5194720
6.40	IC50	398.1	nM	CHEMBL5220077
6.40	IC50	398.1	nM	CHEMBL5220099
6.20	IC50	631	nM	CHEMBL5220904
6.20	IC50	631	nM	CHEMBL5220501
6.20	IC50	631	nM	CHEMBL5220753
6.20	IC50	631	nM	CHEMBL5220275
6.20	IC50	631	nM	CHEMBL1957266
6.17	IC50	670	nM	GSK789
6.10	IC50	794.3	nM	GSK620

PubChem BioAssay actives

65 with measured affinity, of 87 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
(1R)-7-[4-[[(1R)-1,3-dimethyl-2-oxo-1H-3-benzazepin-7-yl]oxy]butoxy]-1,3-dimethyl-1H-3-benzazepin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	<0.0001	uM
(1R)-7-[[4-[[(1R)-1,3-dimethyl-2-oxo-1H-3-benzazepin-7-yl]methyl]piperazin-1-yl]methyl]-1,3-dimethyl-1H-3-benzazepin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0002	uM
(1R)-7-[2-[[(1R)-1,3-dimethyl-2-oxo-1H-3-benzazepin-7-yl]oxy]ethoxy]-1,3-dimethyl-1H-3-benzazepin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0003	uM
(1R)-7-[5-[[(1R)-1,3-dimethyl-2-oxo-1H-3-benzazepin-7-yl]oxy]pentoxy]-1,3-dimethyl-1H-3-benzazepin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0020	uM
(1R)-7-[7-[[(1R)-1,3-dimethyl-2-oxo-1H-3-benzazepin-7-yl]oxy]heptoxy]-1,3-dimethyl-1H-3-benzazepin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0020	uM
(1R)-7-[3-[[(1R)-1,3-dimethyl-2-oxo-1H-3-benzazepin-7-yl]oxy]propoxy]-1,3-dimethyl-1H-3-benzazepin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0020	uM
(3R)-4-[2-[4-[1-(3-methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]ethyl]-1,3-dimethylpiperazin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0032	uM
tert-butyl 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0063	uM
5-[1-(1,3-dimethoxypropan-2-yl)-5-morpholin-4-ylbenzimidazol-2-yl]-1,3-dimethylpyridin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0079	uM
(1R)-7-ethoxy-1,3-dimethyl-5-(2-methyl-1H-imidazol-5-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0158	uM
(1R)-7-ethoxy-1,3-dimethyl-5-(1-methylpyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0199	uM
(1R)-7-ethoxy-1,3-dimethyl-5-(1H-pyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0251	uM
4-acetamido-3-fluoro-N-(4-hydroxycyclohexyl)-5-[(1S)-1-phenylethoxy]benzamide	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0316	uM
(1R)-7-[(1R)-1,2-dihydroxyethyl]-1,3-dimethyl-5-(1H-pyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0316	uM
(1R)-7-(1,3-dihydroxypropan-2-yl)-1,3-dimethyl-5-(1-methylpyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0316	uM
4-[2-(methoxymethyl)-1-[(1R)-1-phenylethyl]-8-[[(3S)-pyrrolidin-3-yl]methoxy]imidazo[4,5-c]quinolin-7-yl]-3,5-dimethyl-1,2-oxazole	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0398	uM
(1R)-7-[(1R)-1,2-dihydroxyethyl]-1,3-dimethyl-5-(1-methylpyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0398	uM
(1R)-7-[(1S)-1,2-dihydroxyethyl]-1,3-dimethyl-5-(1H-pyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0398	uM
(1R)-7-(2-hydroxyethoxy)-1,3-dimethyl-5-(2-methyl-1H-imidazol-5-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0398	uM
(1R)-7-[(1S)-1,2-dihydroxyethyl]-1,3-dimethyl-5-(1-methylpyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0398	uM
(1R)-7-ethylsulfonyl-1,3-dimethyl-5-(1-methylpyrazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0398	uM
7-(3,5-dimethyl-1,2-oxazol-4-yl)-8-methoxy-1-[(1R)-1-pyridin-2-ylethyl]-3H-imidazo[4,5-c]quinolin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0398	uM
(1R)-7,8-dimethoxy-1,3-dimethyl-1H-3-benzazepin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.0501	uM
(1R)-7-ethoxy-5-(1H-imidazol-5-yl)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0501	uM
(1R)-7-ethoxy-1,3-dimethyl-5-(1-methylimidazol-4-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.0501	uM
7-ethoxy-1,3-dimethyl-5-(1H-pyrazol-5-yl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.1259	uM
(1R)-7-ethylsulfonyl-1,3,5-trimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.1585	uM
(2S,4R)-1-acetyl-4-[(5-chloropyrimidin-2-yl)amino]-2-methyl-3,4-dihydro-2H-quinoline-6-carboxamide	1900637: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.1995	uM
(3R)-1,3-dimethyl-4-[2-[4-[1-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)piperidin-4-yl]phenoxy]ethyl]piperazin-2-one	2015578: Inhibition of MCP-1 in LPS-stimulated human PBMC cells pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	0.1995	uM
(2S,4R)-1-acetyl-4-[(5-cyano-2-pyridinyl)amino]-N-ethyl-2-methyl-3,4-dihydro-2H-quinoline-6-carboxamide	1900637: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.2512	uM
(2S,4R)-1-acetyl-4-[(5-chloro-2-pyridinyl)amino]-2-methyl-3,4-dihydro-2H-quinoline-6-carboxamide	1900637: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.3981	uM
(1R)-1,3-dimethyl-7-(morpholin-4-ylmethyl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.3981	uM
(1R)-7-ethylsulfonyl-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.3981	uM
(1R)-7-(1,3-dihydroxypropan-2-yloxy)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.6310	uM
(1R)-7-(1,3-dihydroxypropan-2-yl)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.6310	uM
7-(2-hydroxy-2-methylpropoxy)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.6310	uM
(1R)-1,3-dimethyl-7-(oxan-4-ylmethyl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	0.6310	uM
(1R)-7-(2-methoxyethoxy)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	1.0000	uM
(1R)-7-(2-hydroxyethyl)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	1.0000	uM
(1R)-7-(1,2-dihydroxyethyl)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	1.0000	uM
7-ethylsulfonyl-1,3-dimethyl-5-pyridin-4-yl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	1.2589	uM
(1R)-1,3-dimethyl-7-(pyrrolidin-1-ylmethyl)-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	1.5849	uM
7-ethylsulfonyl-1,3-dimethyl-5-phenyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	1.5849	uM
(2R,3S,4S,5R,6R)-6-[2-(2-aminoethoxy)ethoxy]-3-[(2R,3R,4S,5S,6R)-6-carboxy-5-[(2R,3R,4S,5S,6R)-6-carboxy-5-[(2R,3R,4S,5S,6R)-6-carboxy-4-hydroxy-3,5-disulfooxyoxan-2-yl]oxy-4-hydroxy-3-sulfooxyoxan-2-yl]oxy-4-hydroxy-3-sulfooxyoxan-2-yl]oxy-4-hydroxy-5-sulfooxyoxane-2-carboxylic acid	1823521: Binding affinity to human CCL2 assessed as dissociation constant incubated for 3 mins by surface plasmon resonance analysis	kd	1.6700	uM
(1R)-7-ethylsulfonyl-1,3-dimethyl-2-oxo-1H-3-benzazepine-5-carboxamide	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	1.9953	uM
4-[(1R)-1-aminoethyl]-N-pyridin-4-ylcyclohexane-1-carboxamide	551814: Inhibition of MCP1-mediated human THP cell migration	ic50	2.6303	uM
7-ethoxy-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	3.1623	uM
8-[6-[(1,3-dimethyl-2-oxo-1H-3-benzazepin-8-yl)oxy]hexoxy]-1,3-dimethyl-1H-3-benzazepin-2-one	2015577: Inhibition of MCP-1 in LPS-stimulated human whole blood pretreated with compound for 30 mins followed by LPS-stimulation and measured after 10 mins by microplate analysis	ic50	3.9811	uM
(1R)-1,3-dimethyl-1H-3-benzazepin-2-one	1918628: Inhibition of MCP-1 in LPS-stimulated human whole blood incubate for 24 hrs by immuno assay	ic50	5.0119	uM
5-(1,4-diazepan-1-ylsulfonyl)-2H-isoquinolin-1-one	551814: Inhibition of MCP1-mediated human THP cell migration	ic50	6.9183	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects secretion, decreases reaction, increases reaction, affects reaction, decreases secretion (+3 more)	44
Resveratrol	decreases reaction, increases expression, increases reaction, decreases expression, increases secretion (+2 more)	18
Particulate Matter	decreases secretion, affects cotreatment, increases abundance, increases secretion, increases expression (+3 more)	18
Glucose	affects localization, decreases reaction, increases expression, increases secretion, affects cotreatment (+2 more)	14
sodium arsenite	increases secretion, affects reaction, decreases expression, increases abundance, increases expression (+1 more)	13
SB 203580	decreases reaction, increases expression, increases abundance, increases secretion, decreases secretion (+1 more)	13
Quercetin	increases secretion, affects cotreatment, decreases reaction, increases expression, affects secretion (+2 more)	13
Tretinoin	affects cotreatment, increases expression, increases reaction, decreases expression	10
Hydrogen Peroxide	affects cotreatment, decreases expression, increases reaction, increases secretion, decreases reaction (+1 more)	9
Tetradecanoylphorbol Acetate	decreases reaction, increases expression, increases secretion, affects cotreatment	9
Simvastatin	decreases secretion, decreases response to substance, increases reaction, decreases reaction, increases expression (+3 more)	9
Dexamethasone	affects cotreatment, increases secretion, increases expression, affects binding, decreases expression (+1 more)	8
Tobacco Smoke Pollution	decreases reaction, increases expression, increases reaction, affects cotreatment, decreases expression (+2 more)	8
Estradiol	decreases activity, affects cotreatment, decreases expression, decreases reaction, increases reaction (+5 more)	7
Folic Acid	increases secretion, decreases reaction, decreases expression, affects expression, affects response to substance (+1 more)	7
Tetrachlorodibenzodioxin	decreases reaction, increases expression, increases reaction, increases secretion, decreases expression	7
Cadmium Chloride	increases abundance, increases secretion, affects cotreatment, increases expression, increases reaction (+2 more)	7
bisphenol A	affects expression, affects binding, decreases reaction, increases reaction, increases expression (+2 more)	6
nickel chloride	increases expression, increases reaction, decreases reaction, decreases secretion, increases secretion	6
nickel sulfate	affects cotreatment, increases expression, decreases expression	6
U 0126	decreases activity, decreases secretion, decreases expression, decreases reaction, increases expression (+2 more)	6
Arsenic Trioxide	affects cotreatment, increases expression	6
Acetylcysteine	decreases reaction, decreases secretion, increases expression, increases secretion	6
Vehicle Emissions	affects cotreatment, increases secretion, increases reaction, decreases reaction, decreases secretion (+3 more)	6
Silicon Dioxide	increases reaction, increases secretion, increases expression, decreases reaction, decreases secretion	6
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	6
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases reaction, decreases reaction, increases secretion, increases expression, decreases secretion	5
lipopolysaccharide, E coli O55-B5	increases expression, increases secretion, increases reaction, affects cotreatment, decreases reaction	5
(+)-JQ1 compound	affects binding, decreases reaction, increases reaction, increases expression, decreases expression	5
Air Pollutants	increases expression, increases abundance, affects cotreatment, increases secretion	5

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1647668	Binding	Inhibition of MCP1-mediated human THP cell migration	Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1MH	Abcam HeLa CCL2 KO	Cancer cell line	Female
CVCL_E1FL	Abcam A-549 CCL2 KO	Cancer cell line	Male
CVCL_SH29	HAP1 CCL2 (-) 1	Cancer cell line	Male
CVCL_XM52	HAP1 CCL2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00301587	PHASE3	WITHDRAWN	A Study to Evaluate Folate Levels in Women Taking Oral Contraceptives
NCT00468481	PHASE3	COMPLETED	Efficacy and Safety Study for an Oral Contraceptive Containing Folate
NCT01392989	PHASE2	COMPLETED	Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
NCT00452829	PHASE1	COMPLETED	Prevention of Neural Tube Defects by Inositol in Conjunction With Folic Acid (PONTI Study)
NCT03794011	PHASE1	ACTIVE_NOT_RECRUITING	Patch vs. No Patch Fetoscopic Meningomyelocele Repair Study
NCT00341068	Not specified	TERMINATED	Genetic Analysis of Neural Tube and Orofacial Cleft Defects in the Irish Population
NCT00394862	Not specified	COMPLETED	Efficacy of Weekly Versus Daily Folic Acid Supplementation
NCT01244399	Not specified	COMPLETED	Influence of Espresso on Adsorption of Myo-inositol
NCT01253746	Not specified	UNKNOWN	Genetics of Neural Tube Defects
NCT01743196	Not specified	COMPLETED	Folate Metabolism in Normal Weight and Obese Women of Child-bearing Age
NCT03090633	Not specified	ACTIVE_NOT_RECRUITING	Fetoscopic Repair of Isolated Fetal Spina Bifida
NCT03315637	Not specified	UNKNOWN	Fetal Endoscopic Surgery for Spina Bifida
NCT03856034	Not specified	RECRUITING	Laparotomy Versus Percutaneous Endoscopic Correction of Myelomeningocele
NCT03936322	Not specified	COMPLETED	Minimally Invasive Fetoscopic Regenerative Repair of Spina Bifida - A Pilot Study
NCT04135274	Not specified	COMPLETED	Is Neutrophil to Lymphocyte Ratio a Prognostic Factor of Sepsis in Newborns With Operated Neural Tube Defects?
NCT04140669	Not specified	TERMINATED	Automated Myocardial Performance Index Using Samsung HERA W10
NCT04362592	Not specified	ACTIVE_NOT_RECRUITING	In-Utero Endoscopic Correction of Spina Bifida
NCT04523233	Not specified	UNKNOWN	Metals/Vitamins Levels in NTD
NCT04760509	Not specified	UNKNOWN	Short- Term Follow up Of Neonates Born With Neural Tube Defect
NCT04770805	Not specified	ACTIVE_NOT_RECRUITING	In Utero Fetoscopic Repair Program for Sacral Myelomeningoceles and Mye-LDM
NCT05454085	Not specified	COMPLETED	Could Bisphenol-A Have a Role in the Etiology of Neural Tube Defects
NCT05672849	Not specified	RECRUITING	Safety and Efficacy of Devices Used in Fetoscopic Neural Tube Defect Repair Cases
NCT05883761	Not specified	COMPLETED	Birth Outcomes In Eswatini After Transition To Dolutegravir-Based Treatment
NCT05935631	Not specified	COMPLETED	Feasibility, Acceptability and Directional Signal Effect on Blood Folate Levels of Iodized Salt Fortified With Folic Acid: Clinical Study
NCT06135883	Not specified	COMPLETED	Assessing Folic Acid in High-Risk Pregnancy for Neural Tube Defects
NCT06174883	Not specified	COMPLETED	Salt-FA to Increase Folate Levels
NCT06734611	Not specified	NOT_YET_RECRUITING	Folic Acid Salt Study (FISFA Zambia)
NCT06904612	Not specified	COMPLETED	Using Iodized Salt to Improve Serum Folate, B12 and Iron Levels
NCT06946563	Not specified	RECRUITING	Fetoscopic Neural Tube Defect Repair