CCL5

Summary

CCL5 (C-C motif chemokine ligand 5, HGNC:10632) is a protein-coding gene on chromosome 17q12, encoding C-C motif chemokine 5 (P13501). Chemoattractant for blood monocytes, memory T-helper cells and eosinophils.

This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, functions as a chemoattractant for blood monocytes, memory T helper cells and eosinophils. It causes the release of histamine from basophils and activates eosinophils. This cytokine is one of the major HIV-suppressive factors produced by CD8+ cells. It functions as one of the natural ligands for the chemokine receptor chemokine (C-C motif) receptor 5 (CCR5), and it suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Alternative splicing results in multiple transcript variants that encode different isoforms.

Source: NCBI Gene 6352 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002985

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10632
Approved symbol	CCL5
Name	C-C motif chemokine ligand 5
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	RANTES, SISd, TCP228, MGC17164
Ensembl gene	ENSG00000271503
Ensembl biotype	protein_coding
OMIM	187011
Entrez	6352

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000605140, ENST00000605509, ENST00000651122

RefSeq mRNA: 2 — MANE Select: NM_002985 NM_001278736, NM_002985

CCDS: CCDS11300, CCDS92290

Canonical transcript exons

ENST00000605140 — 3 exons

Exon	Start	End
ENSE00003460965	35871491	35872464
ENSE00003562135	35880230	35880360
ENSE00003581973	35878528	35878639

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 99.67.

FANTOM5 (CAGE): breadth broad, TPM avg 238.7002 / max 31055.2592, expressed in 901 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165403	238.6880	900
165402	0.0121	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.67	gold quality
leukocyte	CL:0000738	99.23	gold quality
monocyte	CL:0000576	99.20	gold quality
blood	UBERON:0000178	98.19	gold quality
lymph node	UBERON:0000029	97.03	gold quality
spleen	UBERON:0002106	96.22	gold quality
gall bladder	UBERON:0002110	94.95	gold quality
duodenum	UBERON:0002114	94.42	gold quality
colonic epithelium	UBERON:0000397	93.70	gold quality
vermiform appendix	UBERON:0001154	93.50	gold quality
bone marrow	UBERON:0002371	93.41	gold quality
bone marrow cell	CL:0002092	92.84	gold quality
mucosa of transverse colon	UBERON:0004991	90.56	gold quality
rectum	UBERON:0001052	89.52	gold quality
small intestine	UBERON:0002108	89.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.93	gold quality
upper lobe of left lung	UBERON:0008952	87.34	gold quality
right uterine tube	UBERON:0001302	87.18	gold quality
right lung	UBERON:0002167	86.81	gold quality
lung	UBERON:0002048	86.07	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.97	gold quality
tonsil	UBERON:0002372	85.40	gold quality
right coronary artery	UBERON:0001625	84.54	gold quality
liver	UBERON:0002107	83.66	gold quality
omental fat pad	UBERON:0010414	83.37	gold quality
body of stomach	UBERON:0001161	82.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.09	gold quality
smooth muscle tissue	UBERON:0001135	82.00	gold quality
fundus of stomach	UBERON:0001160	81.86	gold quality

Single-cell (SCXA)

Detected in 59 experiment(s), a significant marker in 48.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	9434.78
E-CURD-95	yes	8151.01
E-CURD-85	yes	7106.75
E-GEOD-139324	yes	5124.47
E-CURD-89	yes	5121.78
E-HCAD-8	yes	4765.52
E-MTAB-10287	yes	4727.68
E-MTAB-8410	yes	4358.19
E-GEOD-125970	yes	4268.67
E-GEOD-130148	yes	4018.14
E-MTAB-6653	yes	3686.26
E-CURD-126	yes	3490.73
E-MTAB-8207	yes	3437.60
E-MTAB-6701	yes	3260.00
E-CURD-55	yes	3244.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, APP, AR, ATF2, ATF3, CD36, CEBPA, CEBPB, CEBPD, CREB1, DDIT3, ESR1, FOS, HIF1A, IRF1, IRF2, IRF3, IRF5, IRF6, IRF7, IRF8, IRX2, JUN, JUNB, JUND, KLF13, NFATC2, NFKB1, NFKB2, NFKB, NFKBIA, NFKBIB, NR3C1, PLIN3, PPARA, PPARG, PPP2CB, PTPN22, REL, RELA

miRNA regulators (miRDB)

22 targeting CCL5, 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-6778-3P	99.96	67.29	2693
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-645	97.28	66.30	486
HSA-MIR-617	96.79	65.96	738
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-584-5P	95.82	68.05	848
HSA-MIR-1914-3P	95.07	63.37	762
HSA-MIR-758-5P	93.99	64.46	534

Literature-anchored findings (GeneRIF, showing 40)

• Differential production of RANTES and MCP-1 in synovial fluid from the inflamed human knee. (PMID:11750041)
• RANTES levels in blood, quantities released from platelets ex vivo, and quantities released from SFFLRN stimulated platelets ex vivo were compared for preeclamptic and normal pregnancies. (PMID:11816717)
• synthesis was detected in human Leydig cells exposed to the Sendai virus, but not in human total germ cells (PMID:11897701)
• The prototypic inflammatory chemokine RANTES activates a defined transcriptional profile in fresh human monocytes consisting of stimulation of at least 42 genes of 5600 examined. (PMID:11907119)
• We determined that human serum contains a molecule that suppresses RANTES (CCL5) binding to endothelial cells, PBMC and CHO cells. (PMID:11920567)
• A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes. (PMID:12093895)
• modulating influence on HIV/AIDS by interacting with variants (PMID:12114533)
• in infants with respiratory syncytial virus bronchiolitis, the proportion of RANTES relative to IL-8 was significantly increased (PMID:12139952)
• CCR5 protein has a role as a HIV-1 receptor favoring the recruitment of fusiogenic proteins and the formation of a fusion pore. (PMID:12154092)
• TNF-alpha potently induced RANTES secretion, but IL-17 dose-dependently inhibited the TNF-alpha-induced RANTES secretion in human colonic subepithelial myofibroblasts. This was also observed at the mRNA level. (PMID:12165487)
• functional AhR are present in endometrial and endometriotic stromal cells and that TCDD up-regulates the expression of RANTES, providing a possible mechanistic link between dioxin exposure and chemokine expression in endometriosis. (PMID:12200463)
• Expression of RANTES is induced by stimulation of monocytic cells through Fc gamma receptors and involves activation of CCAAT enhancer-binding protein beta sites. (PMID:12218153)
• results demonstrate that both CCR1 and CCR4 are functional receptors on human mast cells with capacity to mediate migration towards CCL5 (PMID:12270118)
• role of viral accessory protein Vpr and Nef in RANTES/CCL5 expression (PMID:12359436)
• role of IL-12 and IFN-gamma on inducing inflammatory chemokine (CCL5) secretion and down-regulating CCR5 expression in human T cells (PMID:12377943)
• The RANTES(9-68)-heparin interaction has been characterized by a complex binding model that involves heparin-induced dimerization of the chemokine through a mechanism of positive cooperativity. (PMID:12475226)
• RANTES expression is regulated by CFTR in airway epithelial cells (PMID:12509457)
• Associations of RANTES polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Hepatitis C virus-seropositive whites with the RANTES -403-A allele were less likely to have severe hepatic inflammation. (PMID:12557141)
• RANTES promoter -28G genotype and CCR5 promoter 59029A genotype may be independent risk factors for diabetic nephropathy in patients with type 2 diabetes and may have an additive effect on nephropathy. (PMID:12610055)
• mast cells may regulate lymphocytic infiltration in basal cell carcinoma through the production of RANTES (PMID:12660426)
• TNF-alpha-induced expression of RANTES plays important roles in cell-mediated liver injury in alcoholic liver diseases. (PMID:12663241)
• RANTES is not upregulated by leptin in human monocytic cells (PMID:12668159)
• Efficient leukocyte arrest in flow but not transmigration may thus require the presentation of RANTES oligomers to bridge surface-bound RANTES and CCR1. (PMID:12763925)
• The RANTES promoter polymorphism is a genetic risk factor for near-fatal asthma in Chinese children. (PMID:12789231)
• case-control study was performed to evaluate the role of -403G –> A and -28C –> G as susceptibility factors for HIV-1 infection in the Spanish population; data consistent with lack of association between these SNPs and HIV-1 infection in this population (PMID:12803993)
• Data suggest that in oral lichen planus, the presence of CCL5 and CXCL10 in the cytolytic granules of tissue-infiltrating CD8(+)T cells expressing CCR5 and CXCR3 reveals a potential self-recruiting mechanism involving activated effector cytotoxic T cells (PMID:12819030)
• Data are consistent with the lack of association between RANTES polymorphisms and endometriosis, but do not exclude a possible role of other variants within the RANTES gene in this pathology. (PMID:12837926)
• A putative signal transduction pathway leading to RANTES production from fibroblasts when the DR molecules were ligated was detected (PMID:12842758)
• dichotomous effects of RANTES on HIV-1 entry at the moment of infection, and on production and spread of virus progeny in primary macrophages (PMID:12960233)
• Two single nucleotide polymorphisms in RANTES promoter region and intron I were found to be associated with the genetic susceptibility to HIV-1 infection among Chinese and the In1.1C allele displayed a stronger association with HIV-1 infection in males. (PMID:14687494)
• RANTES expression and production increase in nasal mucosa (septal and turbinate portions) of allergic patients compared to the same mucosa in non-allergic patients (PMID:14687706)
• peritoneal macrophage stimulation of RANTES production by endometrium stromal cells could lead to a self-propagating recruitment of inflammatory cells that contribute to the development and progression of endometriotic lesions. (PMID:15001640)
• The study results indicated that the -403 and -28 alleles in the RANTES promoter region belong to the predictor gene set for allergic rhinitis and could be used in genomic analysis. (PMID:15064621)
• prior or simultaneous treatment of HEp-2 cells with recombinant human CCL5 provides dose-dependent inhibition of infection with RSV. (PMID:15122808)
• TWEAK acts on human keratinocytes as an inducer of RANTES via Fn14. (PMID:15140220)
• Our results demonstrate that IFNbeta plays a positive regulatory role in the expression of RANTES/CCL5 in human astrocytes through several distinct mechanisms (PMID:15228586)
• CCL% expression frequent in ATL and HTLV-I-infected cell lines; aberrant expression may impact pathophysiology of HTLV-I-associated diseases (PMID:15239133)
• SNP -403G may be associated with increased susceptibility to HIV infection, while -28G may be associated with advanced disease (PMID:15265023)
• A strong upregulation of MCP-1 and RANTES was observed in all the cases, mainly in tubular cells, and there was a strong correlation between the expression of these chemokines and NF-kappaB activation in the same cells. (PMID:15280531)
• RANTES haplotypes might contribute to polygenic interaction between hepatitis C virus and host immune system and could help to risk stratify patients prior to antiviral therapy. (PMID:15368437)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl35.2	ENSDARG00000070378
danio_rerio	ccl35.1	ENSDARG00000103466
mus_musculus	Ccl5	ENSMUSG00000035042

Paralogs (26): CX3CL1 (ENSG00000006210), CCL26 (ENSG00000006606), CCL22 (ENSG00000102962), CCL17 (ENSG00000102970), CCL24 (ENSG00000106178), CCL7 (ENSG00000108688), CCL2 (ENSG00000108691), CCL8 (ENSG00000108700), CCL1 (ENSG00000108702), CCL20 (ENSG00000115009), CCL25 (ENSG00000131142), CCL21 (ENSG00000137077), XCL1 (ENSG00000143184), XCL2 (ENSG00000143185), CCL11 (ENSG00000172156), CCL19 (ENSG00000172724), CCL13 (ENSG00000181374), 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 5 — P13501 (reviewed: P13501)

Alternative names: EoCP, Eosinophil chemotactic cytokine, SIS-delta, Small-inducible cytokine A5, T cell-specific protein P228, T-cell-specific protein RANTES

All UniProt accessions (3): A0A494C1Q1, D0EI67, P13501

UniProt curated annotations — full annotation on UniProt →

Function. Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells.

Subunit / interactions. Homo and heterooligomers with other chemokines. Interacts with the brown dog tick evasin-4.

Subcellular location. Secreted.

Tissue specificity. Expressed in the follicular fluid (at protein level). T-cell and macrophage specific.

Post-translational modifications. N-terminal processed form RANTES(3-68) is produced by proteolytic cleavage, probably by DPP4, after secretion from peripheral blood leukocytes and cultured sarcoma cells. N-terminal processed form RANTES(4-68) is produced by proteolytic cleavage by cathepsin CTSG. The identity of the O-linked saccharides at Ser-27 and Ser-28 are not reported in PubMed:1380064. They are assigned by similarity.

Induction. By mitogens.

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

RefSeq proteins (2): NP_001265665, NP_002976* (*=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 (30 total): mutagenesis site 7, strand 7, chain 3, helix 3, sequence conflict 2, glycosylation site 2, disulfide bond 2, signal peptide 1, sequence variant 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
5COY	X-RAY DIFFRACTION	1.44
6STK	X-RAY DIFFRACTION	1.52
1B3A	X-RAY DIFFRACTION	1.6
1EQT	X-RAY DIFFRACTION	1.6
6AEZ	X-RAY DIFFRACTION	1.63
1U4P	X-RAY DIFFRACTION	1.7
2VXW	X-RAY DIFFRACTION	1.7
1U4L	X-RAY DIFFRACTION	2
1U4M	X-RAY DIFFRACTION	2
1U4R	X-RAY DIFFRACTION	2.2
5UIW	X-RAY DIFFRACTION	2.2
5L2U	X-RAY DIFFRACTION	2.28
5DNF	X-RAY DIFFRACTION	2.55
6LOG	X-RAY DIFFRACTION	2.55
7F1R	ELECTRON MICROSCOPY	3
5CMD	X-RAY DIFFRACTION	3.09
7O7F	ELECTRON MICROSCOPY	3.15
6C6D	X-RAY DIFFRACTION	5.5
1HRJ	SOLUTION NMR
1RTN	SOLUTION NMR
1RTO	SOLUTION NMR
2L9H	SOLUTION NMR, SOLUTION SCATTERING
6FGP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13501-F1	89.51	0.69

Antibody-complex structures (SAbDab): 1 — 7O7F

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 (1): 25–26 (cleavage; by dpp4)

Post-translational modifications (1): 90

Disulfide bonds (2): 33–57, 34–73

Glycosylation sites (2): 27, 28

Mutagenesis-validated functional residues (7):

Position	Phenotype
31	no effect on inhibition of activity by tick evasin-4.
31	reduced inhibition of activity by tick evasin-4.
46	no effect on inhibition of activity by tick evasin-4.
49	no effect on inhibition of activity by tick evasin-4.
55	no effect on inhibition of activity by tick evasin-4.
67–70	no effect on inhibition of activity by tick evasin-4.
78–82	no effect on inhibition of activity by tick evasin-4.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-6783783	Interleukin-10 signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-449147	Signaling by Interleukins
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 767 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_DENDRITIC_CELL_MIGRATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_T_CELL_CHEMOTAXIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, MODULE_169, GOBP_CELL_CHEMOTAXIS, LU_IL4_SIGNALING

GO Biological Process (65): dendritic cell chemotaxis (GO:0002407), monocyte chemotaxis (GO:0002548), regulation of chronic inflammatory response (GO:0002676), calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), exocytosis (GO:0006887), chemotaxis (GO:0006935), inflammatory response (GO:0006954), leukocyte cell-cell adhesion (GO:0007159), G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), response to virus (GO:0009615), response to toxic substance (GO:0009636), positive regulation of macrophage chemotaxis (GO:0010759), positive regulation of T cell chemotaxis (GO:0010820), positive regulation of smooth muscle cell migration (GO:0014911), positive regulation of cell migration (GO:0030335), phospholipase D-activating G protein-coupled receptor signaling pathway (GO:0031583), positive regulation of TOR signaling (GO:0032008), positive regulation of cell-cell adhesion mediated by integrin (GO:0033634), positive regulation of homotypic cell-cell adhesion (GO:0034112), chemokine (C-C motif) ligand 5 signaling pathway (GO:0035689), positive regulation of T cell proliferation (GO:0042102), neutrophil activation (GO:0042119), host-mediated suppression of viral transcription (GO:0043922), cellular response to fibroblast growth factor stimulus (GO:0044344), positive regulation of viral genome replication (GO:0045070), negative regulation of viral genome replication (GO:0045071), positive regulation of innate immune response (GO:0045089), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), positive regulation of G protein-coupled receptor signaling pathway (GO:0045745), positive regulation of cell adhesion (GO:0045785), positive regulation of translational initiation (GO:0045948), eosinophil chemotaxis (GO:0048245), macrophage chemotaxis (GO:0048246), positive regulation of smooth muscle cell proliferation (GO:0048661), epithelial cell proliferation (GO:0050673), positive regulation of epithelial cell proliferation (GO:0050679), regulation of insulin secretion (GO:0050796), regulation of T cell activation (GO:0050863)

GO Molecular Function (16): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), protein kinase activity (GO:0004672), chemokine activity (GO:0008009), phospholipase activator activity (GO:0016004), receptor signaling protein tyrosine kinase activator activity (GO:0030298), CCR1 chemokine receptor binding (GO:0031726), CCR4 chemokine receptor binding (GO:0031729), CCR5 chemokine receptor binding (GO:0031730), chemoattractant activity (GO:0042056), chemokine receptor binding (GO:0042379), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), chemokine receptor antagonist activity (GO:0046817), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
CCR chemokine receptor binding	3
cellular anatomical structure	3
leukocyte chemotaxis	2
response to chemical	2
chemokine receptor binding	2
receptor ligand activity	2
dendritic cell migration	1
mononuclear cell migration	1
myeloid leukocyte migration	1
chronic inflammatory response	1
regulation of inflammatory response	1
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
taxis	1
defense response	1
cell-cell adhesion	1
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
signaling	1
response to other organism	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
T cell chemotaxis	1
regulation of T cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
positive regulation of T cell migration	1
smooth muscle cell migration	1
regulation of smooth muscle cell migration	1
positive regulation of cell migration	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1

Protein interactions and networks

STRING

4024 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL5	CCR2	P41597	999
CCL5	CCR5	P51681	999
CCL5	CCR1	P32246	999
CCL5	CCR3	P51677	999
CCL5	CXCR4	P30991	997
CCL5	PF4	P02776	996
CCL5	CXCR3	P49682	996
CCL5	CXCR2	P25025	993
CCL5	ACKR1	Q16570	993
CCL5	CX3CR1	P49238	982
CCL5	CCR7	P32248	981
CCL5	CCRL2	O00421	962
CCL5	ACKR2	O00590	961
CCL5	CXCL10	P02778	951
CCL5	CXCL9	Q07325	949

IntAct

115 interactions, top by confidence:

A	B	Type	Score
CCL5	CCL5	psi-mi:“MI:0407”(direct interaction)	0.860
CCL5	CCL5	psi-mi:“MI:0914”(association)	0.860
CCR5	CCL5	psi-mi:“MI:0915”(physical association)	0.660
CCL5	CCR5	psi-mi:“MI:0407”(direct interaction)	0.660
CCR5	CCL5	psi-mi:“MI:0407”(direct interaction)	0.660
CCL17	CCL5	psi-mi:“MI:0407”(direct interaction)	0.640
CCL5	CCL17	psi-mi:“MI:0407”(direct interaction)	0.640
CCL17	CCL5	psi-mi:“MI:2364”(proximity)	0.640
CCL5	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL2	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL11	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL13	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL16	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL20	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL21	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (81): CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), CCL5 (Two-hybrid), C4A (Affinity Capture-MS), NTMT1 (Affinity Capture-MS), SPATA20 (Affinity Capture-MS), AK4 (Affinity Capture-MS)

ESM2 similar proteins: A9QWQ1, O14625, O46675, O46676, O46677, O46678, O89098, O97919, P08317, P09340, P09341, P10147, P10855, P10889, P12850, P13236, P13501, P14095, P14097, P16619, P19875, P19876, P30782, P30882, P42831, P46632, P47854, P50229, P50230, P50231, P97272, Q17QA1, Q5EBF6, Q5I1Z0, Q5RA36, Q68A92, Q68AZ0, Q711P4, Q8HYQ1, Q8HYQ2

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

9 interactions.

A	Effect	B	Mechanism
maraviroc	down-regulates	CCL5	“chemical inhibition”
CCL5	up-regulates	CCR1	binding
CCL5	up-regulates	CCR3	binding
IRX2	“down-regulates quantity by repression”	CCL5	“transcriptional regulation”
CCL5	“up-regulates activity”	CCR5	binding
FOXP3	“up-regulates quantity by expression”	CCL5	“transcriptional regulation”
CCL5	up-regulates	Metastasis
CCL5	“down-regulates quantity by repression”	hsa-miR-199a-5p	“post transcriptional regulation”
CCL5	“down-regulates quantity by repression”	hsa-miR-200b-5p	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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	22	105.6×	2e-39
Interleukin-10 signaling	6	35.9×	5e-07
Class A/1 (Rhodopsin-like receptors)	13	24.7×	2e-13
Peptide ligand-binding receptors	13	24.7×	2e-13
GPCR ligand binding	13	21.4×	8e-13
G alpha (i) signalling events	17	17.0×	3e-15
Signaling by GPCR	13	13.4×	3e-10
Signaling by Interleukins	7	11.5×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	9	143.3×	2e-16
chemokine-mediated signaling pathway	18	126.8×	4e-32
monocyte chemotaxis	5	63.2×	7e-07
chemotaxis	21	62.0×	5e-31
antimicrobial humoral immune response mediated by antimicrobial peptide	17	59.9×	2e-24
neutrophil chemotaxis	9	55.9×	3e-12
cell chemotaxis	13	52.3×	1e-17
positive regulation of actin filament polymerization	5	35.9×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	9
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
12740	NM_002985.3(CCL5):c.76+231T>C	Pathogenic

SpliceAI

426 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35872460:CAAAG:C	acceptor_gain	1.0000
17:35872465:C:CC	acceptor_gain	1.0000
17:35878526:A:AC	donor_gain	1.0000
17:35878527:C:CC	donor_gain	1.0000
17:35878527:CA:C	donor_gain	1.0000
17:35878527:CACGA:C	donor_gain	1.0000
17:35872461:AAAG:A	acceptor_gain	0.9900
17:35872462:AAG:A	acceptor_gain	0.9900
17:35872463:AG:A	acceptor_gain	0.9900
17:35872464:GCTG:G	acceptor_loss	0.9900
17:35872465:CT:C	acceptor_loss	0.9900
17:35872466:T:C	acceptor_loss	0.9900
17:35878467:T:TA	donor_gain	0.9900
17:35878638:ATCTG:A	acceptor_loss	0.9900
17:35878639:TCTGG:T	acceptor_loss	0.9900
17:35878640:C:CC	acceptor_gain	0.9900
17:35878640:CT:C	acceptor_loss	0.9900
17:35878641:T:G	acceptor_loss	0.9900
17:35880228:A:AC	donor_gain	0.9900
17:35880229:C:CC	donor_gain	0.9900
17:35878519:GAGAC:G	donor_loss	0.9800
17:35878520:AGAC:A	donor_loss	0.9800
17:35878521:GAC:G	donor_loss	0.9800
17:35878522:ACTCA:A	donor_loss	0.9800
17:35878523:CTCA:C	donor_loss	0.9800
17:35878524:T:TT	donor_loss	0.9800
17:35878525:CACA:C	donor_loss	0.9800
17:35878526:A:C	donor_loss	0.9800
17:35878527:CACG:C	donor_gain	0.9800
17:35878550:TGCC:T	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000156922 (17:35881789 C>T), RS1000165965 (17:35871362 G>A,C), RS1000599672 (17:35873370 G>A), RS1000709472 (17:35877736 T>A), RS1000762147 (17:35880441 A>C), RS1001317972 (17:35875698 C>T), RS1001601648 (17:35872163 T>A), RS1001652338 (17:35871817 C>A), RS1002168067 (17:35878899 T>C), RS1002285422 (17:35874415 C>T), RS1002439570 (17:35881037 T>C), RS1002724355 (17:35874093 T>G), RS1002754843 (17:35877378 CAAAACA>C,CAAAACAAAAACA), RS1003216859 (17:35876934 T>C), RS1003314215 (17:35881919 C>A,T)

Disease associations

OMIM: gene MIM:187011 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_2080	Blood protein levels	2.000000e-54
GCST006585_2902	Blood protein levels	5.000000e-35

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1275217 (SINGLE PROTEIN), CHEMBL3885531 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4796120	CCL5		0.00	0

ChEMBL bioactivities

30 potent at pChembl≥5 of 30 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.77	IC50	17	nM	CHEMBL1270493
7.66	IC50	22	nM	CHEMBL1270595
7.64	IC50	23	nM	CHEMBL1270101
7.64	IC50	23	nM	CHEMBL1269384
7.60	IC50	25	nM	CHEMBL1270798
7.60	IC50	25	nM	CHEMBL1270799
7.60	IC50	25	nM	CHEMBL1270901
7.57	IC50	27	nM	CHEMBL1270594
7.57	IC50	27	nM	CHEMBL1270694
7.57	IC50	27	nM	CHEMBL1271108
7.51	IC50	31	nM	CHEMBL1271208
7.50	IC50	32	nM	CHEMBL1271107
7.50	IC50	32	nM	CHEMBL1269885
7.47	IC50	34	nM	CHEMBL1270901
7.46	IC50	35	nM	CHEMBL1270693
7.46	IC50	35	nM	CHEMBL1270401
7.42	IC50	38	nM	CHEMBL1269385
7.41	IC50	39	nM	CHEMBL1270303
7.40	IC50	40	nM	CHEMBL1270209
7.36	IC50	44	nM	CHEMBL1269885
7.33	IC50	47	nM	CHEMBL1271000
7.32	IC50	48	nM	CHEMBL1269383
7.28	IC50	52	nM	CHEMBL1270494
7.17	IC50	68	nM	CHEMBL1271310
7.14	IC50	72	nM	CHEMBL1271207
6.99	IC50	102	nM	CHEMBL1270900
6.98	IC50	104	nM	CHEMBL1269386
6.68	IC50	207	nM	CHEMBL1269884
6.67	IC50	215	nM	CHEMBL1269387
5.24	Kd	5720	nM	CHEMBL5081237

PubChem BioAssay actives

30 with measured affinity, of 60 total; 28 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
[(3aR,6aS)-2-[3-phenyl-3-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0170	uM
[(3aR,6aS)-2-[3-(1-cyclopentylsulfonylazetidin-3-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0220	uM
[(3aS,6aR)-2-[3-(1-cyclopentylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0230	uM
[(3aR,6aS)-2-[3-phenyl-3-(1-propan-2-ylsulfonylazetidin-3-yl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0230	uM
[(3aR,6aS)-2-[3-[1-(2,2-difluoroethyl)piperidin-4-yl]-3-(3,5-difluorophenyl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0250	uM
[(3aR,6aS)-2-[3-(1-ethylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0250	uM
[(3aR,6aS)-2-[3-(1-methylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0250	uM
[(3aR,6aS)-2-[3-[1-(2,2-difluoroethyl)piperidin-4-yl]-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0270	uM
[(3aR,6aS)-2-[3-(1-cyclopropylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0270	uM
5-[(3aR,6aS)-2-[3-(1-methylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-4,6-dimethylpyran-2-one	527242: Inhibition of RANTES	ic50	0.0270	uM
5-[(3aR,6aS)-2-[3-(1-methylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carbonyl]-4,6-dimethylpyridine-2-carbonitrile	527242: Inhibition of RANTES	ic50	0.0310	uM
[(3aS,6aR)-2-[3-(3-fluorophenyl)-3-(1-methylsulfonylpiperidin-4-yl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0320	uM
1-[4-[3-[(3aS,6aR)-5-(4,6-dimethylpyrimidine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-1-phenylpropyl]piperidin-1-yl]propan-1-one	527242: Inhibition of RANTES	ic50	0.0320	uM
[(3aS,6aR)-2-[3-[1-(2,2-difluoroethyl)piperidin-4-yl]-3-(3-fluorophenyl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0350	uM
[(3aS,6aR)-2-[3-(1-cyclopropylsulfonylazetidin-3-yl)-3-(3,5-difluorophenyl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0350	uM
[(3aS,6aR)-2-[3-[1-(benzenesulfonyl)piperidin-4-yl]-3-(3-fluorophenyl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0380	uM
[(3aR,6aS)-2-[3-(1-cyclopropylsulfonylazetidin-3-yl)-3-(3-fluorophenyl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0390	uM
[(3aR,6aS)-2-[3-(1-cyclopropylsulfonylazetidin-3-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0400	uM
[(3aR,6aS)-2-[3-phenyl-3-(1-propan-2-ylsulfonylpiperidin-4-yl)propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0470	uM
[(3aS,6aR)-2-[3-phenyl-3-[1-(2,2,2-trifluoroethylsulfonyl)piperidin-4-yl]propyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0480	uM
[(3aS,6aR)-2-[3-(1-methylsulfonylazetidin-3-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(4,6-dimethylpyrimidin-5-yl)methanone	527242: Inhibition of RANTES	ic50	0.0520	uM
1-[4-[3-[(3aR,6aS)-5-(4,6-dimethylpyrimidine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-1-phenylpropyl]piperidin-1-yl]-3-methylbutan-1-one	527242: Inhibition of RANTES	ic50	0.0680	uM
1-[4-[3-[(3aS,6aR)-5-(4,6-dimethylpyrimidine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-1-phenylpropyl]piperidin-1-yl]-2-methylpropan-1-one	527242: Inhibition of RANTES	ic50	0.0720	uM
methyl 4-[3-[(3aS,6aR)-5-(4,6-dimethylpyrimidine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-1-phenylpropyl]piperidine-1-carboxylate	527242: Inhibition of RANTES	ic50	0.1020	uM
[(3aS,6aR)-2-[3-(1-methylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-(2-chloro-6-methylphenyl)sulfonylmethanone	527242: Inhibition of RANTES	ic50	0.1040	uM
[3-[3-[(3aS,6aR)-5-(4,6-dimethylpyrimidine-5-carbonyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-1-phenylpropyl]azetidin-1-yl]-cyclopentylmethanone	527242: Inhibition of RANTES	ic50	0.2070	uM
4-[(3aS,6aR)-2-[3-(1-methylsulfonylpiperidin-4-yl)-3-phenylpropyl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carbonyl]sulfonyl-3-chlorobenzonitrile	527242: Inhibition of RANTES	ic50	0.2150	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	1823524: Binding affinity to human CCL5 assessed as dissociation constant incubated for 3 mins by surface plasmon resonance analysis	kd	5.7200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, increases secretion, increases expression, affects cotreatment, increases reaction (+1 more)	15
Particulate Matter	decreases reaction, increases abundance, affects expression, decreases secretion, increases reaction (+4 more)	8
Vehicle Emissions	decreases secretion, increases reaction, increases expression, decreases expression, decreases reaction (+2 more)	7
SB 203580	increases secretion, affects binding, decreases secretion, decreases reaction, increases expression (+1 more)	4
Beclomethasone	decreases reaction, increases secretion, decreases expression, affects cotreatment, decreases secretion	4
Benzo(a)pyrene	increases reaction, increases methylation, affects methylation, increases expression	4
Silicon Dioxide	increases expression, increases secretion	4
Tobacco Smoke Pollution	increases expression, increases reaction, decreases expression, increases secretion, decreases reaction	4
Cadmium Chloride	increases abundance, increases expression, decreases reaction, increases secretion, decreases expression	4
titanium dioxide	affects binding, increases secretion, increases expression	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases expression, affects cotreatment, decreases secretion (+4 more)	3
Fluticasone	increases expression, increases secretion, decreases reaction	3
Acetylcysteine	increases expression, decreases reaction, increases secretion	3
Dust	decreases expression, increases expression, increases secretion	3
Estradiol	decreases expression, increases expression, affects cotreatment	3
Glucose	decreases expression, increases expression, affects cotreatment	3
Methotrexate	decreases expression, increases expression, increases reaction	3
Poly I-C	affects cotreatment, decreases reaction, increases expression, increases reaction	3
sodium arsenite	increases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
nickel sulfate	increases secretion, affects expression	2
Resveratrol	decreases reaction, increases expression	2
Troglitazone	decreases secretion, increases expression	2
Terbinafine	increases expression, increases reaction, affects cotreatment, decreases reaction	2
Air Pollutants	increases secretion, increases abundance, increases expression, affects cotreatment	2
Benzene	increases expression	2
Bezafibrate	decreases reaction, increases expression	2
Cadmium	decreases expression, increases abundance, decreases reaction, increases expression	2
Copper	increases expression, affects binding, affects cotreatment, increases reaction, increases activity	2
Cycloheximide	increases expression, increases reaction, decreases reaction	2

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1272914	Binding	Inhibition of RANTES	Evaluation of amide replacements in CCR5 antagonists as a means to increase intrinsic permeability. Part 2: SAR optimization and pharmacokinetic profile of a homologous azacyle series. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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