CCR8

Summary

CCR8 (C-C motif chemokine receptor 8, HGNC:1609) is a protein-coding gene on chromosome 3p22.1, encoding C-C chemokine receptor type 8 (P51685). G protein-coupled receptor that can bind a variety of chemokines, such as CCL1, CCL8, CCL16, CCL18.

This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptors are important for the migration of various cell types into the inflammatory sites. This receptor protein preferentially expresses in the thymus. I-309, thymus activation-regulated cytokine (TARC) and macrophage inflammatory protein-1 beta (MIP-1 beta) have been identified as ligands of this receptor. Studies of this receptor and its ligands suggested its role in regulation of monocyte chemotaxis and thymic cell apoptosis. More specifically, this receptor may contribute to the proper positioning of activated T cells within the antigenic challenge sites and specialized areas of lymphoid tissues. This gene is located at the chemokine receptor gene cluster region.

Source: NCBI Gene 1237 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 50 total
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 1.95 (unconstrained)
• MANE Select transcript: NM_005201
• Notable: 50 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1609
Approved symbol	CCR8
Name	C-C motif chemokine receptor 8
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	CY6, TER1, CKR-L1, GPR-CY6, CDw198
Ensembl gene	ENSG00000179934
Ensembl biotype	protein_coding
OMIM	601834
Entrez	1237

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000326306

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

ENST00000326306, ENST00000414803

RefSeq mRNA: 1 — MANE Select: NM_005201 NM_005201

CCDS: CCDS2684

Canonical transcript exons

ENST00000326306 — 2 exons

Exon	Start	End
ENSE00001288442	39329709	39329829
ENSE00001288452	39332318	39333680

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 92.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5692 / max 145.6795, expressed in 90 samples.

Highest expression (Bgee): primordial germ cell in gonad, buccal mucosa cell, type B pancreatic cell, diaphragm, granulocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CCR8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	1.7e-19	-0.55	3:39373114:C:T
Whole Blood	eqtl	2.7e-02	+0.59	3:39585858:G:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
36126	0.3647	70
36125	0.1380	47
36127	0.0423	23
36124	0.0240	12

Top tissues by expression

showing 100 of 262 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.66	gold quality
buccal mucosa cell	CL:0002336	68.21	gold quality
type B pancreatic cell	CL:0000169	67.00	gold quality
diaphragm	UBERON:0001103	63.08	gold quality
granulocyte	CL:0000094	61.26	gold quality
periodontal ligament	UBERON:0008266	60.79	gold quality
vermiform appendix	UBERON:0001154	59.28	gold quality
mucosa of urinary bladder	UBERON:0001259	57.61	gold quality
gall bladder	UBERON:0002110	57.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	56.70	gold quality
caecum	UBERON:0001153	56.46	gold quality
trabecular bone tissue	UBERON:0002483	54.84	gold quality
lymph node	UBERON:0000029	54.61	gold quality
ileal mucosa	UBERON:0000331	54.07	silver quality
skin of hip	UBERON:0001554	53.60	silver quality
thymus	UBERON:0002370	53.26	gold quality
upper leg skin	UBERON:0004262	52.65	silver quality
epithelial cell of pancreas	CL:0000083	52.06	gold quality
blood	UBERON:0000178	50.82	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
quadriceps femoris	UBERON:0001377	50.27	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
pancreatic ductal cell	CL:0002079	50.06	silver quality
vastus lateralis	UBERON:0001379	49.32	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
deltoid	UBERON:0001476	48.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
cervix epithelium	UBERON:0004801	48.49	gold quality
oviduct epithelium	UBERON:0004804	48.44	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
nasal cavity epithelium	UBERON:0005384	48.16	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality
kidney epithelium	UBERON:0004819	47.32	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
rectum	UBERON:0001052	45.68	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
tonsil	UBERON:0002372	45.34	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
bone marrow cell	CL:0002092	44.97	gold quality
skeletal muscle tissue	UBERON:0001134	44.89	gold quality
cardia of stomach	UBERON:0001162	44.83	gold quality
tibialis anterior	UBERON:0001385	44.40	silver quality
trachea	UBERON:0003126	43.77	gold quality
lower lobe of lung	UBERON:0008949	43.64	silver quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
epithelium of bronchus	UBERON:0002031	43.23	gold quality
bronchus	UBERON:0002185	43.10	gold quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
urinary bladder	UBERON:0001255	42.50	gold quality
metanephros	UBERON:0000081	42.32	gold quality
nasal cavity mucosa	UBERON:0001826	42.14	gold quality
cartilage tissue	UBERON:0002418	42.04	gold quality
epithelium of nasopharynx	UBERON:0001951	41.98	gold quality
cranial nerve II	UBERON:0000941	41.77	silver quality
medulla oblongata	UBERON:0001896	41.74	gold quality
trigeminal ganglion	UBERON:0001675	41.43	gold quality
epithelium of mammary gland	UBERON:0003244	41.43	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
bone marrow	UBERON:0002371	41.03	gold quality
ventral tegmental area	UBERON:0002691	41.01	gold quality
duodenum	UBERON:0002114	40.89	silver quality
pleura	UBERON:0000977	40.81	gold quality
spleen	UBERON:0002106	40.80	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
dorsal plus ventral thalamus	UBERON:0001897	40.56	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
mammary duct	UBERON:0001765	40.10	gold quality
tongue	UBERON:0001723	40.09	gold quality
liver	UBERON:0002107	40.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
bronchial epithelial cell	CL:0002328	39.88	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	580.64
E-ANND-3	no	2.76

HPA expression

RNA tissue specificity: Tissue enriched

53 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	7.2	medium
Urinary bladder	tissue	1.2	not detected
Appendix	tissue	0.9	not detected
Lymph node	tissue	0.6	not detected
Gallbladder	tissue	0.6	not detected
Tonsil	tissue	0.6	not detected
Lung	tissue	0.5	not detected
Spleen	tissue	0.5	not detected
Amygdala	tissue	0.4
Periaqueductal gray	tissue	0.4
Skin 1	tissue	0.3	not detected
Stomach 1	tissue	0.3	not detected
Rectum	tissue	0.3	not detected
Basal ganglia	tissue	0.3	not detected
Choroid plexus	tissue	0.3
Hippocampal formation	tissue	0.3
Prefrontal cortex	tissue	0.2
Cerebral cortex	tissue	0.2	not detected
Pons	tissue	0.2
Esophagus	tissue	0.2	not detected
Colon	tissue	0.2	not detected
Hypothalamus	tissue	0.2
Small intestine	tissue	0.2	not detected
Spinal cord	tissue	0.2
Corpus callosum	tissue	0.2
Ventral forebrain	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Olfactory bulb	tissue	0.2
Septum	tissue	0.2
Somatosensory cortex	tissue	0.2
Retrosplenial cortex	tissue	0.2
Temporal cortex	tissue	0.2
Cervix	tissue	0.1	not detected
Breast	tissue	0.1	not detected
Heart muscle	tissue	0.1	not detected
Adipose tissue	tissue	0.1	not detected
Salivary gland	tissue	0.1	not detected
Pancreas	tissue	0.1	not detected
Motor cortex	tissue	0.1
Putamen	tissue	0.1
Nucleus accumbens	tissue	0.1
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1
Thalamus	tissue	0.1
Superior colliculi	tissue	0.1
Cerebellum	tissue	0.1	not detected
Substantia nigra	tissue	0.1
Thyroid gland	tissue	0.1	not detected
Locus coeruleus	tissue	0.1
Hippocampus	tissue	0.1	not detected
Postcentral gyrus	tissue	0.1
Entorhinal cortex	tissue	0.1
Insular cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 183; highest nTPM — Nucleus raphe pallidus (0.3), Nucleus tractus solitarii (0.3), Subiculum (0.3), Anterior cochlear nucleus, ventral (0.2), Anterior insular cortex, dorsal (0.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT6

miRNA regulators (miRDB)

Targeting CCR8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

16 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-4642	97.52	67.60	916

Functional genomics

gnomAD constraint: pLI 0.0167, LOEUF 1.95, missense Z 1.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000326306 — one region, missense o/e 0.86.

Literature-anchored findings (GeneRIF, showing 35)

• CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway (PMID:12525579)
• found in the central nervous system and is associated with phagocytic macrophages (PMID:12547701)
• CCR8 genes and surrounding genomic regions these genes are the result of the duplication of an ancestral gene prior to the divergence of teleost fish. (PMID:12551893)
• Transfected human CCR8-dependent activation of the RAS/MAPK pathway mediates anti-apoptotic activity of I-309/ CCL1 and vMIP-I. (PMID:12645948)
• The induction of CCR8 under conditions associated with vascular smooth muscle cell proliferation and migration raises the possibility that CCR8 may play an important role in vessel wall pathology. (PMID:14576057)
• the axis CCL1-CCR8 links adaptive and innate immune functions that play a role in the initiation and amplification of atopic skin inflammation (PMID:15814739)
• CCR8 ligands are allotropic, binding to distinct sites within CCR8; the human immune system may have evolved to use CCL7 as a selective antagonist of viral chemokine activity at CCR8 but not those of the host ligand (PMID:17023422)
• CCR8 is expressed by a small and heterogeneous population of peripheral blood CD4 memory T cells enriched in T helper type 2 (Th2) effector and T regulatory (Treg) cells. (PMID:17082609)
• CCR8-expressing CD4-positive T lymphocytes are preferentially recruited from the periphery into the lungs of asthmatic individuals, driven by elevated CCL1 levels produced almost exclusively by mast cells and basophils. (PMID:17641040)
• The combination of 17beta-E(2) with the environmental pollutant TCDD is involved in the pathogenesis of endometriosis via up-regulating the chemokine CCR8-I-309. (PMID:17693327)
• There may be a role for CCR8 in the recruitment of T cells to the lung in asthmatics. (PMID:20455898)
• The functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in chronic obstructive pulmonary disease patients. (PMID:21976223)
• C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity (PMID:22479563)
• Data show that CCR8 expression by newly activated naive T cells is regulated by skin-specific factor(s) derived primarily from epidermal keratinocytes. (PMID:23043070)
• CCR8(+) myeloid cell subset is expanded in patients with cancer. (PMID:23363815)
• CCL1-CCR8 interaction may play a critical role in lymphocytic recruitment in IgG4-related sclerosing cholangitis and type 1 autoimmune pancreatitis, leading to duct-centred inflammation and obliterative phlebitis. (PMID:23811304)
• Identification of human CCR8 as a CCL18 receptor. (PMID:23999500)
• findings suggest that CCR8 expression in ALCL is more closely related to the presence of DUSP22 rearrangements than to cutaneous involvement and that the function of CCR8 may extend beyond its skin-homing properties in this disease (PMID:25390351)
• Epidermal-derived vitamin D3 metabolites and prostaglandins provide an essential cue for the localization of CCR8+ immune surveillance T cells within healthy human skin. (PMID:26002980)
• High CCR8 expression is associated with high recurrence in kidney cancer. (PMID:26716905)
• Role of Conserved Disulfide Bridges and Aromatic Residues in Extracellular Loop 2 of Chemokine Receptor CCR8 for Chemokine and Small Molecule Binding. (PMID:27226537)
• Authors demonstrate the pivotal role of CCR8(+) Treg cells in restraining immunity and highlight the potential clinical implications of this discovery. (PMID:28533380)
• Long-lived memory T cells in human skin can be defined by the expression of CCR8. (PMID:29427415)
• Blocking CCR8 via a small molecule inhibitor or short hairpin (sh)RNA mitigated the decrease in Ecadherin, and increase in MMP2 and VEGFC, caused by human recombinant (r)CCL18. CCR8 knockdown by shRNA reversed rCCL18induced cancer cell invasion, migration and epithelialmesenchymal transition (PMID:30592282)
• ARNT-dependent CCR8 reprogrammed LDH isoform expression correlates with poor clinical outcomes of prostate cancer. (PMID:32319143)
• Clinical and prognostic significance of CC chemokine receptor type 8 protein expression in gastrointestinal stromal tumors. (PMID:32884223)
• Chemokine (C-C Motif) Ligand 1 Derived from Tumor-Associated Macrophages Contributes to Esophageal Squamous Cell Carcinoma Progression via CCR8-Mediated Akt/Proline-Rich Akt Substrate of 40 kDa/Mammalian Target of Rapamycin Pathway. (PMID:33460563)
• Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway. (PMID:34025655)
• Chemokine CCL18 Promotes Phagocytosis Through Its Receptor CCR8 Rather than PITPNM3 in Human Microglial Cells. (PMID:35041514)
• CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory. (PMID:35140181)
• Differential expression of CCR8 in tumors versus normal tissue allows specific depletion of tumor-infiltrating T regulatory cells by GS-1811, a novel Fc-optimized anti-CCR8 antibody. (PMID:36352891)
• Development of a cellular model to study CCR8 signaling in tumor-infiltrating regulatory T cells. (PMID:38231448)
• Unveiling the structural mechanisms of nonpeptide ligand recognition and activation in human chemokine receptor CCR8. (PMID:38306437)
• Cryo-EM Structure and Biochemical Analysis of the Human Chemokine Receptor CCR8. (PMID:38985857)
• The chemokine receptor CCR8 is not a high-affinity receptor for the human chemokine CCL18. (PMID:39259753)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccr8.2	ENSDARG00000086616
danio_rerio	ccr8.1	ENSDARG00000095789
danio_rerio	si:cabz01093077.1	ENSDARG00000105467
mus_musculus	Ccr8	ENSMUSG00000042262
rattus_norvegicus	Ccr8	ENSRNOG00000026759

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1201402) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased anxiety-related response	1
decreased locomotor activity	1
abnormal eye morphology	1
decreased susceptibility to experimental autoimmune encephalomyelitis	1
abnormal behavior	1
decreased thigmotaxis	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Trachypithecus phayrei	O97879	100.0%	Diamond
Pongo pygmaeus	O97881	100.0%	Diamond
Pan troglodytes	P56440	100.0%	Diamond
Pan paniscus	P60574	100.0%	Diamond
Lophocebus aterrimus	P61755	100.0%	Diamond
Pongo abelii	P61756	100.0%	Diamond
Semnopithecus entellus	P61757	100.0%	Diamond
Macaca mulatta	P61813	100.0%	Diamond
Macaca fascicularis	P61814	100.0%	Diamond
Macaca nemestrina	P61815	100.0%	Diamond
Papio anubis	P68269	100.0%	Diamond
Papio hamadryas	P68270	100.0%	Diamond
Cercocebus atys	O62743	99.7%	Diamond
Trachypithecus francoisi	O97878	99.7%	Diamond
Rhinopithecus bieti	O97880	99.7%	Diamond
Rhinopithecus avunculus	O97962	99.7%	Diamond
Macaca arctoides	O97975	99.7%	Diamond
Gorilla gorilla gorilla	P56439	99.7%	Diamond
Saimiri sciureus	Q8HZU0	99.7%	Diamond
Callithrix jacchus	Q8HZU1	99.7%	Diamond
Hylobates moloch	Q95NC0	99.7%	Diamond
Theropithecus gelada	Q95NC1	99.7%	Diamond
Symphalangus syndactylus	Q95NC5	99.7%	Diamond
Nasalis larvatus	Q95NC7	99.7%	Diamond
Colobus polykomos	Q95NC8	99.7%	Diamond
Chlorocebus aethiops	Q9TSQ8	99.7%	Diamond
Cercocebus galeritus	Q9TV49	99.7%	Diamond
Pygathrix nemaeus	O97882	99.4%	Diamond
Nomascus leucogenys	O97883	99.4%	Diamond
Trachypithecus johnii	Q95NC6	99.4%	Diamond
Mandrillus sphinx	Q95ND1	99.4%	Diamond
Mandrillus leucophaeus	Q95ND2	99.4%	Diamond
Chlorocebus tantalus	Q95NE8	99.4%	Diamond
Allochrocebus solatus	Q9BGN6	99.4%	Diamond
Chlorocebus pygerythrus	Q9TV42	99.4%	Diamond
Allochrocebus lhoesti	Q9XT76	99.4%	Diamond
Miopithecus talapoin	Q95NC3	99.1%	Diamond
Erythrocebus patas	Q95ND0	99.1%	Diamond
Chlorocebus sabaeus	Q9TV43	99.1%	Diamond
Cercopithecus cephus	Q9TV47	99.1%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
CX3CR1	protein-coding	1524
DSTNP4	protein-coding	729454

Protein

Protein identifiers

C-C chemokine receptor type 8 — P51685 (reviewed: P51685)

Alternative names: CC chemokine receptor CHEMR1, CMKBRL2, Chemokine receptor-like 1, GPR-CY6, TER1

All UniProt accessions (2): C9JIP9, P51685

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor that can bind a variety of chemokines, such as CCL1, CCL8, CCL16, CCL18. Regulates monocyte and eosinophil chemotaxis. Undergoes internalization upon CCL18 binding, leading to induced migration and calcium flux of highly polarized Th2 cells. In microglial cells, promotes phagocytosis with CCL18 through NF-kappa-B and Src signaling pathways. Stimulation of the CCL1-CCR8 signaling axis protects the gut from acute intestinal damage. (Microbial infection) Acts as a coreceptor for HIV-1 and HIV-2 viruses. (Microbial infection) Acts as a receptor for Kaposi virus protein vCCL1/K6 and thereby inhibits apoptosis in the targeted cells.

Subunit / interactions. Interacts with GNAI1. (Microbial infection) Interacts with Kaposi virus proteins vCCL1 and vCCL2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in unstimulated CD4(+) and CD8(+) T-cells and polymorphonuclear cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P51685-1	1	yes
P51685-2	2

RefSeq proteins (1): NP_005192* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR004068	Chemokine_CCR8	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (40 total): helix 13, topological domain 8, transmembrane region 7, mutagenesis site 3, strand 3, disulfide bond 2, chain 1, splice variant 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
8XML	Cryo-EM structure of the Apo CCR8-Gi complex	ELECTRON MICROSCOPY	2.58
8TLM	Structure of a class A GPCR/Fab complex	ELECTRON MICROSCOPY	2.9
8KFX	Gi bound CCR8 complex with nonpeptide agonist LMD-009	ELECTRON MICROSCOPY	2.96
8KFY	Gi bound CCR8 complex with nonpeptide agonist ZK 756326	ELECTRON MICROSCOPY	3.06
8U1U	Structure of a class A GPCR/agonist complex	ELECTRON MICROSCOPY	3.1
8KFZ	Gi bound CCR8 in ligand free state	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51685-F1	82.21	0.57

Antibody-complex structures (SAbDab)

6 antibodies co-crystallized with this protein: 8KFX, 8KFY, 8KFZ, 8TLM, 8U1U, 8XML

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Disulfide bonds (2)

Type	Positions
Disulfide bond	25–272, 106–183

Mutagenesis-validated functional residues (3)

Position	Phenotype
113	strong decrease in ability to mediate calcium mobilization.
172	strong decrease in ability to mediate calcium mobilization.
286	strong decrease in ability to mediate calcium mobilization.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-380108	Chemokine receptors bind chemokines	curated
R-HSA-418594	G alpha (i) signalling events	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 122 (showing top): GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, MODULE_64, GOCC_CELL_SURFACE, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, MODULE_289, chr3p22, GAVIN_FOXP3_TARGETS_CLUSTER_P3, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_SIDE_OF_MEMBRANE, BOCHKIS_FOXA2_TARGETS, GOMF_CYTOKINE_BINDING, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY

GO Biological Process (11): chemotaxis (GO:0006935), immune response (GO:0006955), cell adhesion (GO:0007155), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), cell chemotaxis (GO:0060326), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), chemokine-mediated signaling pathway (GO:0070098), cellular response to cytokine stimulus (GO:0071345)

GO Molecular Function (6): G protein-coupled receptor activity (GO:0004930), chemokine receptor activity (GO:0004950), coreceptor activity (GO:0015026), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

35 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway	BP	direct assay
G protein-coupled receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,010 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR8	CCL1	P22362	792
CCR8	CD4	P01730	714
CCR8	ULBP1	Q9BZM6	684
CCR8	MICB	P79525	684
CCR8	ULBP2	Q9BZM5	672
CCR8	ULBP3	Q9BZM4	665
CCR8	STAT5B	P51692	658
CCR8	KLRK1	P26718	637
CCR8	CCL2	P13500	635
CCR8	CCL17	Q92583	632
CCR8	CCL18	P55774	620
CCR8	HCST	Q9UBK5	616
CCR8	FOXP3	Q9BZS1	616
CCR8	LTA	P01374	614
CCR8	STAT5A	P42229	614

IntAct

Human interaction partners of CCR8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

16 partners by confidence:

Partner	Interaction type	MIscore	Records
RAMP2	physical association	0.400	3
RAMP3	physical association	0.400	3
RAMP1	physical association	0.400	2
ATP2A1	physical association	0.370	1
EI24	physical association	0.370	1
ERGIC3	physical association	0.370	1
GABBR1	physical association	0.370	1
GABRD	physical association	0.370	1
NAGPA	physical association	0.370	1
PAQR6	physical association	0.370	1
PLEKHB1	physical association	0.370	1
RTN3	physical association	0.370	1
SPNS1	physical association	0.370	1
SPP1	physical association	0.370	1
THY1	physical association	0.370	1
UCKL1	physical association	0.370	1

BioGRID (14 interactions; top human partners by supporting records): ATP2A1 (Two-hybrid), EI24 (Two-hybrid), ERGIC3 (Two-hybrid), GABBR1 (Two-hybrid), GABRD (Two-hybrid), NAGPA (Two-hybrid), PAQR6 (Two-hybrid), PLEKHB1 (Two-hybrid), RTN3 (Two-hybrid), SPNS1 (Two-hybrid), SPP1 (Two-hybrid), THY1 (Two-hybrid), UCKL1 (Two-hybrid), USP2 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CCL1	up-regulates	CCR8	binding

Ligand–receptor pairs (CellPhoneDB) (3)

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

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CCL16	receptor	Signaling by Chemokines
CCL1	receptor	Signaling by Chemokines
CCL18	receptor	Signaling by Chemokines

Disease & clinical

Genetic variants

Variant evidence for CCR8: 50 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	4
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 245):

Position(s)	Effect	Δscore	Sites
3:39332316–39332317	acceptor_loss	1.0000	6
3:39329831	donor_loss	0.9900
3:39332309	acceptor_gain	0.9800
3:39329830	donor_loss	0.9600
3:39332301	acceptor_gain	0.9600
3:39329830	donor_loss	0.9500
3:39332603–39332604	acceptor_loss	0.9500	6
3:39332602	acceptor_loss	0.9200
3:39329831	donor_loss	0.8900
3:39332573	acceptor_loss	0.8100

AlphaMissense

644 missense substitutions predicted likely pathogenic (of 2,356 scored), across 188 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D81	8	0.940	0.975
D130	8	0.933	0.972
N53	8	0.930	0.981
F307	8	0.909	0.991
D71	8	0.848	0.901
F90	8	0.794	0.919
F123	8	0.724	0.851
C106	7	0.974	0.990
C183	7	0.974	0.990
W99	7	0.967	0.995
R131	7	0.924	0.974
F101	7	0.909	0.943
W158	7	0.908	0.993
N296	7	0.882	0.974
C272	7	0.866	0.917
W251	7	0.830	0.959
F117	7	0.818	0.951
F254	7	0.811	0.951
C25	7	0.808	0.885
H292	7	0.803	0.944

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:601834 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST007932_22	Medication use (thyroid preparations)	4e-11
GCST003518_93	Daytime sleep phenotypes	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4596 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 761 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2205807	ABAMETAPIR	4	761

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
vMIP-I	Full agonist	9.9	pIC50
CCL1	Full agonist	9.8	pIC50
[125I]CCL1 (human)	Full agonist	9.7	pKd
vMCC-I	Antagonist	9.41	pIC50
[125I]CCL1 (mouse)	Full agonist	8.7	pKd
vMIP-II	Antagonist	8.1	pIC50
ZK 756326	Full agonist	5.7	pIC50

Binding affinities (BindingDB)

212 measured of 248 human assays (248 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-(4-benzoylamino-naphthalene-1-sulfonylamino)-piperidine-1-carboxylic acid ethyl ester	KI	0.17 nM
N-(4-{[(1-butyrylpiperidin-4-yl)amino]sulfonyl}-1-naphthyl)-2-methylbenzamide	IC50	0.3 nM
4-[4-(2-methyl-benzoylamino)-naphthalene-1-sulfonylamino]-piperidine-1-carboxylic acid methylamide	KI	0.7 nM
2-methyl-N-{4-[({1-[(2S)-pyrrolidin-2-ylcarbonyl]piperidin-4-yl}amino)sulfonyl]-1-naphthyl}benzamide)	KI	0.7 nM
2-(3-((1-(3-(2-chlorophenoxy)benzyl)piperidin-4-yl)carbamoyl)-3-phenylpyrrolidin-1-yl)-2-methylpropanoic acid	IC50	1 nM
CHEMBL5424187	IC50	1 nM
2-methyl-N-[4-({[1-(pyrrolidin-1-ylcarbonyl)piperidin-4-yl]-amino}sulfonyl)-1-naphthyl]benzamide	KI	1.1 nM
CHEMBL5404620	IC50	1.2 nM
CHEMBL5397693	IC50	1.3 nM
N-[4-({[1-(azetidin-3-ylcarbonyl)piperidin-4-yl]amino}sulfonyl)-1-naphthyl]-2-methyl-benzamide	KI	1.5 nM
4-({[4-(benzoylamino)-1-naphthyl]sulfonyl}amino)-N,N-dimethylpiperidine-1-carboxamide	KI	1.6 nM
4-[4-(2-methyl-benzoylamino)-naphthalene-1-sulfonylamino]-piperidine-1-carboxylic acid ethyl ester	KI	1.6 nM
N-{4-[1-(4-amino-butyryl)-piperidin-4-ylsulfamoyl]-naphthalen-1-yl}-2-methyl-benzamide	KI	1.6 nM
CHEMBL5411391	IC50	1.7 nM
CHEMBL5412884	IC50	1.7 nM
4-[4-(2-methyl-benzoylamino)-naphthalene-1-sulfonylamino]-piperidine-1-carboxylic acid ethylamide	KI	2.2 nM
ethyl 4-({[5-(benzoylamino)-1-naphthyl]sulfonyl}amino)-piperidine-1-carboxylate	KI	2.3 nM
CHEMBL567417	IC50	2.4 nM
2-methyl-N-[4-(1-propionyl-piperidin-4-ylsulfamoyl)-naphthalen-1-yl]-benzamide	KI	2.5 nM
CHEMBL568523	IC50	2.63 nM
CHEMBL579072	IC50	2.63 nM
CHEMBL568294	IC50	2.82 nM
N-{4-[1-(azetidine-1-carbonyl)-piperidin-4-ylsulfamoyl]-naphthalen-1-yl}-2-methyl-benzamide	KI	3.5 nM
2-(4-{1-[3-(2-chloro-phenoxy)-benzyl]-piperidin-4-ylcarbamoyl}-4-phenyl-piperidin-1-yl)-2-methyl-propionic acid	IC50	4 nM
2-methyl-N-{4-[1-(4-methyl-piperazine-1-carbonyl)-piperidin-4-ylsulfamoyl]-aphthalen-1-yl}-benzamide	IC50	4 nM
CHEMBL5399936	IC50	4 nM
N-{4-[1-(2-amino-acetyl)-piperidin-4-ylsulfamoyl]-naphthalen-1-yl}-2-methyl-benzamide	KI	4.1 nM
2-methyl-N-{4-[1-(piperidine-1-carbonyl)-piperidin-4-ylsulfamoyl]-naphthalen-1-yl}-benzamide	KI	4.2 nM
3-pyrrolidin-1-ylpropyl 4-[({4-[(2-methylbenzoyl)amino]-1-naphthyl}sulfonyl)amino]piperidine-1-carboxylate	IC50	4.2 nM
N-(4-cyclohexylsulfamoyl-naphthalen-1-yl)-benzamide	KI	4.4 nM
CHEMBL574655	IC50	4.9 nM
N-(4-{[(1-butyrylpiperidin-4-yl)amino]sulfonyl}-1-naphthyl)-3-methylbenzamide	IC50	5.1 nM
4-(4-o-tolylcarbamoyl-naphthalene-1-sulfonylamino)-piperidine-1-carboxylic acid ethyl ester	KI	5.21 nM
N-{4-[1-(2-hydroxy-acetyl)-piperidin-4-ylsulfamoyl]-naphthalen-1-yl}-2-methyl-benzamide	KI	5.4 nM
CHEMBL568522	IC50	5.62 nM
CHEMBL5404280	IC50	6 nM
CHEMBL5412094	IC50	6 nM
cyclohexanecarboxylic acid [4-(1-butyryl-piperidin-4-ylsulfamoyl)-naphthalen-1-yl]-amide	IC50	6.1 nM
2-methyl-N-[4-({[1-(morpholin-4-ylcarbonyl)piperidin-4-yl]-amino}sulfonyl)-1-naphthyl]benzamide	KI	6.3 nM
CHEMBL584087	IC50	6.61 nM
N-(4-{[(1-acetylpiperidin-4-yl)amino]sulfonyl}-1-naphthyl)-2-methylbenzamide	KI	6.7 nM
4-tert-butyl-N-(4-{[(1-butyrylpiperidin-4-yl)amino]sulfonyl}-1-naphthyl)benzamide	IC50	6.9 nM
N-[4-(1-cyclopropanecarbonyl-piperidin-4-ylsulfamoyl)-naphthalen-1-yl]-2-methyl-benzamide	KI	7.2 nM
N-(4-{[(1-butyrylpiperidin-4-yl)amino]sulfonyl}-1-naphthyl)-2-phenylbutanamide	IC50	7.65 nM
CHEMBL566543	IC50	8.13 nM
N-[4-(1-cyclopentanecarbonyl-piperidin-4-ylsulfamoyl)-naphthalen-1-yl]-2-methyl-benzamide	KI	9.1 nM
N-(4-{[(1-butyrylpiperidin-4-yl)amino]sulfonyl}-1-naphthyl)-4-methylbenzamide	IC50	9.5 nM
4-(4-cyclohexylcarbamoyl-naphthalene-1-sulfonylamino)-piperidine-1-carboxylic acid ethyl ester	KI	9.5 nM
3-(dimethylamino)propyl 4-[({4-[(2-methylbenzoyl)amino]-1-naphthyl}sulfonyl)amino]piperidine-1-carboxylate	IC50	9.8 nM
N-(4-{[(1-butyrylpiperidin-4-yl)amino]sulfonyl}-1-naphthyl)-4-ethylbenzamide	IC50	10.8 nM

ChEMBL bioactivities

248 potent at pChembl≥5 of 256 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.77	Ki	0.17	nM	CHEMBL218374
9.52	Ki	0.3	nM	CHEMBL374939
9.52	IC50	0.3	nM	CHEMBL374939
9.15	Ki	0.7	nM	CHEMBL386308
9.15	Ki	0.7	nM	CHEMBL221865
9.00	IC50	1	nM	CHEMBL205993
9.00	Ki	1	nM	CHEMBL386308
9.00	IC50	1	nM	CHEMBL5424187
8.96	Ki	1.1	nM	CHEMBL373739
8.92	IC50	1.2	nM	CHEMBL5404620
8.89	IC50	1.3	nM	CHEMBL5397693
8.82	Ki	1.5	nM	CHEMBL375854
8.80	Ki	1.6	nM	CHEMBL218375
8.80	Ki	1.6	nM	CHEMBL221867
8.80	Ki	1.6	nM	CHEMBL376910
8.77	IC50	1.7	nM	CHEMBL5411391
8.77	IC50	1.7	nM	CHEMBL5412884
8.66	Ki	2.2	nM	CHEMBL220701
8.64	Ki	2.3	nM	CHEMBL218037
8.62	IC50	2.399	nM	CHEMBL567417
8.60	Ki	2.5	nM	CHEMBL220753
8.58	IC50	2.63	nM	CHEMBL568523
8.58	IC50	2.63	nM	CHEMBL579072
8.55	IC50	2.818	nM	CHEMBL568294
8.46	Ki	3.5	nM	CHEMBL221130
8.40	IC50	4	nM	CHEMBL380492
8.40	IC50	4	nM	CHEMBL5399936
8.40	IC50	4	nM	CHEMBL221251
8.39	Ki	4.1	nM	CHEMBL221904
8.38	Ki	4.2	nM	CHEMBL221251
8.38	Ki	4.2	nM	CHEMBL385108
8.38	IC50	4.2	nM	CHEMBL374527
8.36	Ki	4.4	nM	CHEMBL218503
8.31	IC50	4.898	nM	CHEMBL574655
8.29	IC50	5.1	nM	CHEMBL221790
8.28	Ki	5.21	nM	CHEMBL375315
8.27	Ki	5.4	nM	CHEMBL218036
8.25	IC50	5.623	nM	CHEMBL568522
8.22	Ki	6	nM	CHEMBL205993
8.22	IC50	6	nM	CHEMBL5404280
8.22	IC50	6	nM	CHEMBL5412094
8.21	IC50	6.1	nM	CHEMBL221586
8.20	Ki	6.3	nM	CHEMBL218218
8.18	IC50	6.607	nM	CHEMBL584087
8.17	Ki	6.7	nM	CHEMBL221977
8.16	IC50	6.9	nM	CHEMBL218297
8.14	Ki	7.2	nM	CHEMBL374979
8.12	IC50	7.65	nM	CHEMBL220652
8.09	IC50	8.128	nM	CHEMBL566543
8.07	IC50	8.44	nM	CHEMBL5407071

PubChem BioAssay actives

248 with measured affinity, of 392 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
ethyl 4-[(4-benzamidonaphthalen-1-yl)sulfonylamino]piperidine-1-carboxylate	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0002	uM
N-[4-[(1-butanoylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0003	uM
2-methyl-N-[4-[[1-[(2S)-pyrrolidine-2-carbonyl]piperidin-4-yl]sulfamoyl]naphthalen-1-yl]benzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0007	uM
N-methyl-4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0007	uM
2-[3-[[1-[[3-(2-chlorophenoxy)phenyl]methyl]piperidin-4-yl]carbamoyl]-3-phenylpyrrolidin-1-yl]-2-methylpropanoic acid	264168: Inhibition of I309-induced chemotaxis in L1.2 cells expressing CCR8	ic50	0.0010	uM
N-[2-chloro-6-methyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]-2-methylbenzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0010	uM
2-methyl-N-[4-[[1-(pyrrolidine-1-carbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]benzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0011	uM
2-methyl-N-[4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]naphthalen-1-yl]benzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0012	uM
3-chloro-2-methyl-N-[2-methyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]benzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0013	uM
N-[4-[[1-(azetidine-3-carbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0015	uM
ethyl 4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxylate	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0016	uM
N,N-dimethyl-4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0016	uM
N-[4-[[1-(4-aminobutanoyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0016	uM
4-chloro-2-methyl-N-[2-methyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]benzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0017	uM
5-chloro-2-methyl-N-[2-methyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]benzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0017	uM
N-ethyl-4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0022	uM
ethyl 4-[(5-benzamidonaphthalen-1-yl)sulfonylamino]piperidine-1-carboxylate	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0023	uM
(5-amino-2-pyridinyl)-[9-[(2-ethyl-2-propyl-3H-1-benzofuran-4-yl)methyl]-3,9-diazaspiro[5.5]undecan-3-yl]methanone	442859: Antagonist activity at human CCR8	ic50	0.0024	uM
2-methyl-N-[4-[(1-propanoylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]benzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0025	uM
(5-amino-2-pyridinyl)-[9-[(2,2-dimethyl-3H-1-benzofuran-7-yl)methyl]-3,9-diazaspiro[5.5]undecan-3-yl]methanone	442859: Antagonist activity at human CCR8	ic50	0.0026	uM
(5-amino-2-pyridinyl)-[9-[(3,3-difluoro-2,2-dimethyl-1-benzofuran-7-yl)methyl]-3,9-diazaspiro[5.5]undecan-3-yl]methanone	442859: Antagonist activity at human CCR8	ic50	0.0026	uM
(5-amino-2-pyridinyl)-[9-[(2-tert-butyl-2-methyl-3H-1-benzofuran-4-yl)methyl]-3,9-diazaspiro[5.5]undecan-3-yl]methanone	442859: Antagonist activity at human CCR8	ic50	0.0028	uM
N-[4-[[1-(azetidine-1-carbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0035	uM
2-[4-[[1-[[3-(2-chlorophenoxy)phenyl]methyl]piperidin-4-yl]carbamoyl]-4-phenylpiperidin-1-yl]-2-methylpropanoic acid	264168: Inhibition of I309-induced chemotaxis in L1.2 cells expressing CCR8	ic50	0.0040	uM
2-methyl-N-[4-[[1-(4-methylpiperazine-1-carbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]benzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0040	uM
N-[2,5-dimethyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]-2-methylbenzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0040	uM
N-[4-[[1-(2-aminoacetyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0041	uM
3-pyrrolidin-1-ylpropyl 4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxylate	277748: Antagonist activity against human CCR8 expressed in CHO/Galpha16 cells assessed as inhibition of CCL1-induced increase of intracellular calcium by FLIPR assay	ic50	0.0042	uM
2-methyl-N-[4-[[1-(piperidine-1-carbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]benzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0042	uM
N-[4-(cyclohexylsulfamoyl)naphthalen-1-yl]benzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0044	uM
[9-[[3-(2-methoxyphenoxy)phenyl]methyl]-3,9-diazaspiro[5.5]undecan-3-yl]-pyrimidin-4-ylmethanone	442859: Antagonist activity at human CCR8	ic50	0.0049	uM
N-[4-[(1-butanoylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]-3-methylbenzamide	277748: Antagonist activity against human CCR8 expressed in CHO/Galpha16 cells assessed as inhibition of CCL1-induced increase of intracellular calcium by FLIPR assay	ic50	0.0051	uM
ethyl 4-[[4-[(2-methylphenyl)carbamoyl]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxylate	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0052	uM
N-[4-[[1-(2-hydroxyacetyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0054	uM
(2-amino-4-pyridinyl)-[9-[(2,2-dimethylchromen-8-yl)methyl]-3,9-diazaspiro[5.5]undecan-3-yl]methanone	442859: Antagonist activity at human CCR8	ic50	0.0056	uM
N-[5-chloro-2-methyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]-2-methylbenzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0060	uM
N-[5-fluoro-2-methyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]-2-methylbenzamide	2029995: Antagonist activity against CCR8 (unknown origin) expressed in CHO-K1 cells preincubated for 1 hr followed by CCL1 addition measured after 24 hrs by ONE-Glo assay	ic50	0.0060	uM
N-[4-[(1-butanoylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]cyclohexanecarboxamide	277748: Antagonist activity against human CCR8 expressed in CHO/Galpha16 cells assessed as inhibition of CCL1-induced increase of intracellular calcium by FLIPR assay	ic50	0.0061	uM
2-methyl-N-[4-[[1-(morpholine-4-carbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]benzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0063	uM
(2-amino-4-pyridinyl)-[9-[(2,2-dimethyl-1,3-benzodioxol-4-yl)methyl]-3,9-diazaspiro[5.5]undecan-3-yl]methanone	442859: Antagonist activity at human CCR8	ic50	0.0066	uM
N-[4-[(1-acetylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0067	uM
N-[4-[(1-butanoylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]-4-tert-butylbenzamide	277748: Antagonist activity against human CCR8 expressed in CHO/Galpha16 cells assessed as inhibition of CCL1-induced increase of intracellular calcium by FLIPR assay	ic50	0.0069	uM
N-[4-[[1-(cyclopropanecarbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0072	uM
N-[4-[(1-butanoylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]-2-phenylbutanamide	277748: Antagonist activity against human CCR8 expressed in CHO/Galpha16 cells assessed as inhibition of CCL1-induced increase of intracellular calcium by FLIPR assay	ic50	0.0076	uM
(5-amino-2-pyridinyl)-[9-[(2,2-dimethyl-3H-1-benzofuran-4-yl)methyl]-3,9-diazaspiro[5.5]undecan-3-yl]methanone	442859: Antagonist activity at human CCR8	ic50	0.0081	uM
2-methyl-N-[2-methyl-4-[[(1R)-1-(1-methylpiperidin-4-yl)ethyl]sulfamoyl]phenyl]benzamide	2030002: Inhibition of CCR8 (unknown origin)-mediated beta-arrestin downstream signalling in CCL1-induced CHO cells assessed as beta-lactamase level by Tango assay	ic50	0.0084	uM
N-[4-[[1-(cyclopentanecarbonyl)piperidin-4-yl]sulfamoyl]naphthalen-1-yl]-2-methylbenzamide	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0091	uM
ethyl 4-[[4-(cyclohexylcarbamoyl)naphthalen-1-yl]sulfonylamino]piperidine-1-carboxylate	277746: Binding affinity to human CCR8 expressed in L1.2 cells by FMAT assay	ki	0.0095	uM
N-[4-[(1-butanoylpiperidin-4-yl)sulfamoyl]naphthalen-1-yl]-4-methylbenzamide	277748: Antagonist activity against human CCR8 expressed in CHO/Galpha16 cells assessed as inhibition of CCL1-induced increase of intracellular calcium by FLIPR assay	ic50	0.0095	uM
3-(dimethylamino)propyl 4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxylate	277748: Antagonist activity against human CCR8 expressed in CHO/Galpha16 cells assessed as inhibition of CCL1-induced increase of intracellular calcium by FLIPR assay	ic50	0.0098	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
nickel sulfate	affects expression, increases expression	2
fluorene-9-bisphenol	increases expression	1
terbufos	increases methylation	1
hydroxyhydroquinone	decreases expression	1
zinc chloride	decreases expression	1
ferrous sulfate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
1-nitropyrene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Calcium	affects abundance	1
Cyclophosphamide	decreases expression	1
Fonofos	increases methylation	1
Methapyrilene	increases methylation	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Soot	decreases expression	1

ChEMBL screening assays

41 unique, capped per target: 23 binding, 18 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1045844	Functional	Antagonist activity at human CCR8	Increasing selectivity of CC chemokine receptor 8 antagonists by engineering nondesolvation related interactions with the intended and off-target binding sites. — *J Med Chem*
CHEMBL2039639	Binding	Inhibition of human CCR8 by FLIPR analysis	The design and synthesis of novel, potent and orally bioavailable N-aryl piperazine-1-carboxamide CCR2 antagonists with very high hERG selectivity. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

10 cell lines: 5 cancer cell line, 3 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1R22	NP-2/CCR8	Cancer cell line	Male
CVCL_1R28	NP-2/CD4/CCR8	Cancer cell line	Male
CVCL_C8V8	4DE4-CCR8	Cancer cell line
CVCL_E6A2	CHO-CCR8	Spontaneously immortalized cell line	Female
CVCL_E6AC	HEK293-CCR8	Transformed cell line	Female
CVCL_E6P6	Genomeditech CHO-K1 H_CCR8	Spontaneously immortalized cell line	Female
CVCL_E6TD	Genomeditech HEK-293 H_CCR8	Transformed cell line	Female
CVCL_E6VP	Genomeditech Jurkat H_CCR8	Cancer cell line	Male
CVCL_KW62	PathHunter CHO-K1 CCR8 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_S494	GHOST(3).CCR8	Cancer cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CCR8 across ~30M SureChEMBL compounds — explore on Sugi Predict.