CX3CR1

Summary

CX3CR1 (C-X3-C motif chemokine receptor 1, HGNC:2558) is a protein-coding gene on chromosome 3p22.2, encoding CX3C chemokine receptor 1 (P49238). Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune response, inflammation, cell adhesion and chemotaxis.

Fractalkine is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by this gene is a receptor for fractalkine. The encoded protein also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to HIV-1 infection and rapid progression to AIDS. Four transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 1524 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 53 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2558
Approved symbol	CX3CR1
Name	C-X3-C motif chemokine receptor 1
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	CMKDR1, V28, CCRL1
Ensembl gene	ENSG00000168329
Ensembl biotype	protein_coding
OMIM	601470
Entrez	1524

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000358309, ENST00000399220, ENST00000412814, ENST00000435290, ENST00000541347, ENST00000542107, ENST00000864857, ENST00000864858, ENST00000864859, ENST00000963325

RefSeq mRNA: 4 — MANE Select: NM_001337 NM_001171171, NM_001171172, NM_001171174, NM_001337

CCDS: CCDS43069, CCDS54571

Canonical transcript exons

ENST00000399220 — 2 exons

Exon	Start	End
ENSE00001537013	39279954	39280036
ENSE00001777225	39263496	39266518

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.86.

FANTOM5 (CAGE): breadth broad, TPM avg 7.6852 / max 761.5493, expressed in 302 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41747	6.3390	291
41751	1.1769	163
41749	0.0894	30
41750	0.0486	24
41748	0.0313	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.86	gold quality
inferior vagus X ganglion	UBERON:0005363	98.52	gold quality
superior vestibular nucleus	UBERON:0007227	97.89	gold quality
leukocyte	CL:0000738	97.68	gold quality
mononuclear cell	CL:0000842	97.54	gold quality
monocyte	CL:0000576	97.50	gold quality
ventral tegmental area	UBERON:0002691	96.58	gold quality
subthalamic nucleus	UBERON:0001906	95.83	gold quality
medulla oblongata	UBERON:0001896	94.86	gold quality
trigeminal ganglion	UBERON:0001675	94.01	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.49	gold quality
CA1 field of hippocampus	UBERON:0003881	93.26	gold quality
dorsal root ganglion	UBERON:0000044	93.23	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.15	gold quality
endothelial cell	CL:0000115	92.24	gold quality
blood	UBERON:0000178	92.14	gold quality
mammary duct	UBERON:0001765	91.84	gold quality
epithelium of mammary gland	UBERON:0003244	91.57	gold quality
cranial nerve II	UBERON:0000941	91.46	gold quality
adult organism	UBERON:0007023	90.36	gold quality
pons	UBERON:0000988	89.84	gold quality
entorhinal cortex	UBERON:0002728	88.94	gold quality
orbitofrontal cortex	UBERON:0004167	88.90	gold quality
palpebral conjunctiva	UBERON:0001812	88.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.63	gold quality
inferior olivary complex	UBERON:0002127	88.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.28	gold quality
substantia nigra pars compacta	UBERON:0001965	87.94	gold quality
trabecular bone tissue	UBERON:0002483	87.92	gold quality
middle frontal gyrus	UBERON:0002702	87.21	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	1122.87
E-CURD-122	yes	41.48
E-ANND-3	yes	13.73
E-MTAB-9067	yes	11.50
E-MTAB-6678	yes	10.49
E-GEOD-130148	yes	4.26
E-GEOD-75367	no	247.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CX3CL1, HIF1A, NFATC1, NFATC2, PPARG, TNF

miRNA regulators (miRDB)

76 targeting CX3CR1, 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-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-4672	99.50	71.58	2893

Literature-anchored findings (GeneRIF, showing 40)

• CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion (PMID:11909868)
• Fractalkine receptor CX3CR1 is selectively expressed on various lineages of lymphocytes with high contents of intracellular perforin and granzyme B. (PMID:12055230)
• CX3CR1 was up-regulated during chronic injury in areas of portal and lobular inflammation. (PMID:12076860)
• CX3CR1 has a role in the accumulation of intrarenal inflammatory cells in kidney diseases (PMID:12110009)
• CX3CR1 gene is controlled by three distinct promoter regions, which are regulated by their respective untranslated exons and that lead to the transcription of three mature messengers (PMID:12234253)
• a difference in genotype frequencies of the V249I and T280M polymorphisms in CX(3)CR1 between peripheral arterial disease patients and controls could not be detected (PMID:12535747)
• a subset of mononuclear cells expresses high levels of fractalkine in human coronary atherosclerotic plaques and smooth muscle cells within the neointima express the fractalkine receptor CX3CR1 (PMID:14581400)
• Two novel CX3CR1 isforms are described that have increased sensitivity to their CX3CL1 and HIV gp120 ligands in binding and functional assays (PMID:14607932)
• upregulated in circulating CD4(+) T lymphocytes in symptomatic allergic rhinitis and asthmatic patients (PMID:14657873)
• existence of CX(3)CR1 (fractalkine receptor) in ejaculated sperm and present findings suggest that fractalkine in the Fallopian tube contributes to immunodefence mechanism during fertilization and to sperm motion in the oviduct (PMID:14747189)
• the naturally occurring Ile249-Met280 variant of the chemokine receptor CX3CR1 has enhanced adhesive capacities (PMID:14990582)
• Polymorphisms of CX3CR1 are a genetic risk factor for internal carotid artery occlusive disease. (PMID:15118174)
• fractalkine (FKN) and CX(3)CR1 expression in the skin, serum sFKN levels, and CX(3)CR1 expression on blood leukocytes in patients with atopic dermatitis (PMID:15131578)
• A decrease, caused by sequence variation (V249I, T280M) and/or lower CX3CR1 expression, in CX3CR1-induced cellular activities could contribute to age-related macular degeneration development. (PMID:15208270)
• CX3CR1-fractalkine expression regulates cellular mechanisms involved in adhesion, migration, and survival of human prostate cancer cells. (PMID:15256432)
• Interleukin (IL)-15 and IL-2 reciprocally regulate expression of the chemokine receptor CX3CR1 through selective NFAT1- and NFAT2-dependent mechanisms (PMID:15347678)
• Replacement of the fractalkine N terminus with the cognate domain of vMIP-II disrupted the ability of FKN to bind CX3CR1. (PMID:15361546)
• distribution assessed in endometrium across the menstrual cycle, in early pregnancy & in women using progestin-only contraceptives; colocalized with CX3CL1 to glandular epithelium and decidualized stromal cells, with highest expression in secretory phase (PMID:15579768)
• We propose that the extra adhesion of monocytes observed in individuals carrying rare alleles of CX3CR1 may favor mechanisms leading to stroke. (PMID:15681302)
• Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. (PMID:15726664)
• V249I polymorphism is not associated wiwth hepatocellular carcinoma. (PMID:15809764)
• The impact of CX3CR1 polymorphisms on HIV-1 pathogenesis and infection progression in children is reported. (PMID:15871132)
• CX3CR1 receptor polymorphisms V249I and T280M have opposite effects in the development of acute coronary syndrome (PMID:15886814)
• CX3CR1 is downregulated in patients with multiple sclerosis (PMID:16144955)
• CX3CL1/CX3CR1 dyad may contribute to atherogenesis and plaque destabilization in human coronary artery disease (PMID:16224053)
• CX3CR1 249I variant allele is more frequent in Spanish HIV-1-infected long-term nonprogressors of more than 15 years (PMID:16284527)
• In heart transplantation, outcomes of early and late rejection episodes may be influenced by genetic variant interactions such as “CX3CR1 249I*CCR5 No-E” and “CCR5 E*RANTES -403A.” (PMID:16314800)
• CX3CR1 is critically dependent on the two negatively charged residues Asp25 and Glu254 located on the N-terminal domain and third extracellular loop, respectively. (PMID:16317113)
• Genetic variation of the fractalkine CXC3R1 system could be involved in systemic sclerosis-associated pulmonary arterial hypertension. (PMID:16584113)
• Presence of M280 polymorphism of fractalkine receptor CX3CR1 is associated with decreased common carotid artery intima-media thickness. Presence of I249 polymorphism does not play major role on progression of carotid atherosclerosis. (PMID:16675737)
• Polymorphisms related to a functional decrease in ligand binding activity of CX3CR1 are associated with disease in patients with retinal vasculitis. (PMID:16799040)
• Results may explain at the molecular and cell biology levels the genetic link between CX3CR1 and atherosclerosis. (PMID:16908772)
• CX3CR1 may play an important role in the development of interstitial fibrosis via mononuclear cell-induced cytokine production chronic kidney graft rejection. (PMID:16979977)
• role for the CX3CL1-CX3CR1 system in the pathogenesis of psoriasis (PMID:17002687)
• Five CX3CR1 single nucleotide polymorphisms have significant associations between their common alleles and asthma. (PMID:17082760)
• increased production of fractalkine by mucosal microvascular cells and increased numbers of circulating and mucosal CX3CR1+ cells in IBD point to a significant role of FKN in disease pathogenesis (PMID:17241867)
• CX3CR1 and CX3CL1 mediate heterotypic anchorage of foam cells to coronary artery smooth muscle cells in the context of atherosclerosis (PMID:17456471)
• Interactions with FKN via chemotactic and adhesive processes might contribute to accumulation of CD16+ monocytes expressing CX3CR1 at synovial tissue of rheumatoid arthritis and continuation of inflammation at site. (PMID:17471309)
• Short-term exposure of MSCs to 1% oxygen increased expression of the chemokine receptors CX3CR1and CXCR4, both as mRNA and as protein (PMID:17476338)
• Amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. (PMID:17505143)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cx3cr1	ENSMUSG00000052336
rattus_norvegicus	Cx3cr1	ENSRNOG00000018509

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), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

CX3C chemokine receptor 1 — P49238 (reviewed: P49238)

Alternative names: Beta chemokine receptor-like 1, Fractalkine receptor, G-protein coupled receptor 13, V28

All UniProt accessions (3): C9JLM2, C9JN40, P49238

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune response, inflammation, cell adhesion and chemotaxis. CX3CR1-CX3CL1 signaling mediates cell migratory functions. Responsible for the recruitment of natural killer (NK) cells to inflamed tissues. Acts as a regulator of inflammation process leading to atherogenesis by mediating macrophage and monocyte recruitment to inflamed atherosclerotic plaques, promoting cell survival. Involved in airway inflammation by promoting interleukin 2-producing T helper (Th2) cell survival in inflamed lung. Involved in the migration of circulating monocytes to non-inflamed tissues, where they differentiate into macrophages and dendritic cells. Acts as a negative regulator of angiogenesis, probably by promoting macrophage chemotaxis. Plays a key role in brain microglia by regulating inflammatory response in the central nervous system (CNS) and regulating synapse maturation. Required to restrain the microglial inflammatory response in the CNS and the resulting parenchymal damage in response to pathological stimuli. Involved in brain development by participating in synaptic pruning, a natural process during which brain microglia eliminates extra synapses during postnatal development. Synaptic pruning by microglia is required to promote the maturation of circuit connectivity during brain development. Acts as an important regulator of the gut microbiota by controlling immunity to intestinal bacteria and fungi. Expressed in lamina propria dendritic cells in the small intestine, which form transepithelial dendrites capable of taking up bacteria in order to provide defense against pathogenic bacteria. Required to initiate innate and adaptive immune responses against dissemination of commensal fungi (mycobiota) component of the gut: expressed in mononuclear phagocytes (MNPs) and acts by promoting induction of antifungal IgG antibodies response to confer protection against disseminated C.albicans or C.auris infection. Also acts as a receptor for C-C motif chemokine CCL26, inducing cell chemotaxis. (Microbial infection) Acts as a coreceptor with CD4 for HIV-1 virus envelope protein. (Microbial infection) Acts as a coreceptor with CD4 for HIV-1 virus envelope protein. May have more potent HIV-1 coreceptothr activity than isoform 1. (Microbial infection) Acts as a coreceptor with CD4 for HIV-1 virus envelope protein. May have more potent HIV-1 coreceptor activity than isoform 1.

Subunit / interactions. Found in a ternary complex with CX3CL1 and ITGAV:ITGB3 or ITGA4:ITGB1. (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) protein G; this interaction modulates host immune response. (Microbial infection) Interacts with HIV-1 envelope polyprotein gp160.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in lymphoid and neural tissues. Expressed in lymphocyte subsets, such as natural killer (NK) cells, gamma-delta T-cells and terminally differentiated CD8(+) T-cells. Expressed in smooth muscle cells in atherosclerotic plaques.

Post-translational modifications. This protein is not N-glycosylated which is unusual for G-protein-coupled receptors.

Disease relevance. Macular degeneration, age-related, 12 (ARMD12) [MIM:613784] A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. Expression is down-regulated by miR-27a-5p microRNA in natural killer (NK) cell lymphocytes in response to TGF-beta1.

Polymorphism. Variations in CX3CR1 are associated with rapid progression to AIDS [MIM:609423]. Increased susceptibility to HIV infection and rapid progression to AIDS are associated with the Ile-249/Met-280 haplotype.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P49238-1	1	yes
P49238-2	2
P49238-3	3
P49238-4	4

RefSeq proteins (4): NP_001164642, NP_001164643, NP_001164645, NP_001328* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR005387	Chemokine_CX3CR1	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (47 total): helix 13, topological domain 8, transmembrane region 7, sequence variant 6, turn 4, splice variant 3, strand 2, chain 1, modified residue 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7XBW	ELECTRON MICROSCOPY	2.8
7XBX	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49238-F1	80.66	0.40

Functional residue map

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

Post-translational modifications (1): 346

Disulfide bonds (1): 102–175

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions

MSigDB gene sets: 478 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_BEHAVIOR, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, ZHAN_MULTIPLE_MYELOMA_MF_UP, GOBP_MACROPHAGE_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, MODULE_45

GO Biological Process (50): positive regulation of neuroblast proliferation (GO:0002052), adaptive immune response (GO:0002250), microglial cell activation involved in immune response (GO:0002282), response to ischemia (GO:0002931), chemotaxis (GO:0006935), immune response (GO:0006955), cellular defense response (GO:0006968), cell adhesion (GO:0007155), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), brain development (GO:0007420), response to wounding (GO:0009611), negative regulation of angiogenesis (GO:0016525), calcium-mediated signaling (GO:0019722), central nervous system maturation (GO:0021626), leukocyte chemotaxis (GO:0030595), regulation of tumor necrosis factor production (GO:0032680), negative regulation of interleukin-1 beta production (GO:0032691), social behavior (GO:0035176), autocrine signaling (GO:0035425), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), regulation of nitric oxide biosynthetic process (GO:0045428), regulation of synaptic plasticity (GO:0048167), host-mediated modulation of intestinal microbiota composition (GO:0048874), regulation of neurogenesis (GO:0050767), positive regulation of neurogenesis (GO:0050769), modulation of chemical synaptic transmission (GO:0050804), leukocyte tethering or rolling (GO:0050901), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), synapse maturation (GO:0060074), cell chemotaxis (GO:0060326), antifungal innate immune response (GO:0061760), cellular response to lipopolysaccharide (GO:0071222), positive regulation of monocyte chemotaxis (GO:0090026), synapse pruning (GO:0098883), negative regulation of hippocampal neuron apoptotic process (GO:0110091), multiple spine synapse organization, single dendrite (GO:0150090)

GO Molecular Function (10): G protein-coupled receptor activity (GO:0004930), chemokine receptor activity (GO:0004950), G protein-coupled peptide receptor activity (GO:0008528), C-C chemokine receptor activity (GO:0016493), C-X3-C chemokine receptor activity (GO:0016495), C-C chemokine binding (GO:0019957), C-X3-C chemokine binding (GO:0019960), CX3C chemokine receptor binding (GO:0031737), cytokine receptor activity (GO:0004896), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), neuronal cell body membrane (GO:0032809), neuron projection (GO:0043005), perinuclear region of cytoplasm (GO:0048471), dendritic tree (GO:0097447), macropinosome membrane (GO:0160056), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Respiratory Syncytial Virus Infection Pathway	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemokine binding	3
cellular anatomical structure	3
immune response	2
response to stress	2
G protein-coupled receptor activity	2
G protein-coupled receptor signaling pathway	2
central nervous system development	2
transmembrane signaling receptor activity	2
chemokine receptor activity	2
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
microglial cell activation	1
macrophage activation involved in immune response	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
defense response	1
cellular process	1
signal transduction	1
phospholipase C activator activity	1
regulation of biological quality	1
cell communication	1
signaling	1
animal organ development	1
head development	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
intracellular signaling cassette	1
anatomical structure maturation	1
leukocyte migration	1
cell chemotaxis	1
tumor necrosis factor production	1
regulation of tumor necrosis factor superfamily cytokine production	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1

Protein interactions and networks

STRING

2622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CX3CR1	CX3CL1	P78423	999
CX3CR1	CCL2	P13500	996
CX3CR1	CCL5	P13501	982
CX3CR1	CD200	P41217	974
CX3CR1	CXCL12	P48061	974
CX3CR1	CCL26	Q9Y258	968
CX3CR1	CCL21	O00585	950
CX3CR1	CXCL1	P09341	950
CX3CR1	CXCL16	Q9H2A7	926
CX3CR1	CD47	Q08722	915
CX3CR1	CCL3	P10147	912
CX3CR1	CCL19	Q99731	910
CX3CR1	CXCL10	P02778	872
CX3CR1	CCL25	O15444	862
CX3CR1	CCL20	P78556	818

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CX3CR1	CX3CL1	psi-mi:“MI:0915”(physical association)	0.400
CX3CR1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
CX3CR1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CX3CR1	psi-mi:“MI:0915”(physical association)	0.400
ITGA4	CX3CR1	psi-mi:“MI:0914”(association)	0.350
ITGB3	CX3CR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): CX3CR1 (Co-localization), CCDC167 (Two-hybrid), CX3CR1 (Co-crystal Structure), HNRNPDL (Cross-Linking-MS (XL-MS)), CX3CR1 (Co-fractionation)

ESM2 similar proteins: A6QNL7, O00574, O18793, O18983, O19024, O54814, O55193, O62743, O97879, O97880, O97882, P32246, P35343, P35407, P35411, P49238, P51675, P51677, P51678, P51683, P56440, P56482, P56483, P56492, P60574, P61757, Q1ZY22, Q2HJ17, Q2KTE1, Q2Y2P0, Q5ECR9, Q64H34, Q6WN98, Q8HZT9, Q95NC2, Q95NC4, Q95NC6, Q95NC7, Q95NC9, Q9BDS6

Diamond homologs: A6QNL7, F5HF62, O00590, O08556, O08707, O09027, O18793, O54689, O54814, O55193, O62743, O97571, O97665, O97878, O97879, O97880, O97881, O97882, O97883, O97962, O97975, P21109, P25025, P32246, P35344, P35411, P41597, P46094, P49238, P51675, P51676, P51677, P51678, P51679, P51680, P51681, P51682, P51683, P51684, P51685

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CX3CL1	up-regulates	CX3CR1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

230 predictions. Top by Δscore:

Variant	Effect	Δscore
3:39266515:AGGC:A	acceptor_gain	1.0000
3:39266516:GGCC:G	acceptor_loss	1.0000
3:39266517:GC:G	acceptor_gain	1.0000
3:39266517:GCC:G	acceptor_loss	1.0000
3:39266518:CC:C	acceptor_gain	1.0000
3:39266519:C:CA	acceptor_loss	1.0000
3:39266520:T:A	acceptor_loss	1.0000
3:39266525:C:CT	acceptor_gain	1.0000
3:39266526:A:T	acceptor_gain	1.0000
3:39266514:AAGGC:A	acceptor_gain	0.9900
3:39266516:GGC:G	acceptor_gain	0.9900
3:39266519:C:CC	acceptor_gain	0.9900
3:39266519:C:T	acceptor_gain	0.9900
3:39280398:A:AC	donor_gain	0.9900
3:39280399:C:CC	donor_gain	0.9900
3:39280399:CTGGA:C	donor_gain	0.9700
3:39266516:GGCCT:G	acceptor_gain	0.9400
3:39266517:GCCTG:G	acceptor_gain	0.9400
3:39266515:AGGCC:A	acceptor_gain	0.9200
3:39266518:CCTGG:C	acceptor_gain	0.9100
3:39266519:C:A	acceptor_gain	0.9100
3:39266520:T:G	acceptor_gain	0.8900
3:39280391:AGTAC:A	donor_loss	0.8600
3:39280392:GTAC:G	donor_loss	0.8600
3:39280393:TACTC:T	donor_loss	0.8600
3:39280394:A:AT	donor_loss	0.8600
3:39280395:CTC:C	donor_loss	0.8600
3:39280396:T:TC	donor_loss	0.8600
3:39280397:C:CG	donor_loss	0.8600
3:39280398:ACT:A	donor_loss	0.8600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000158472 (3:39289276 C>T), RS1000217524 (3:39286886 A>C), RS1000324850 (3:39280993 C>T), RS1000363577 (3:39286432 T>C), RS1000377638 (3:39268468 C>G,T), RS1000416174 (3:39286583 G>A,C), RS1000432375 (3:39284157 G>A,C), RS1000448166 (3:39270780 C>T), RS1000591828 (3:39280736 C>G,T), RS1000621891 (3:39292335 C>T), RS1000668013 (3:39263764 C>G), RS1000823754 (3:39272079 T>C,G), RS1000948424 (3:39279208 CA>C), RS1000956628 (3:39263360 G>T), RS1000994032 (3:39292014 A>C)

Disease associations

OMIM: gene MIM:601470 | disease phenotypes: MIM:609423, MIM:607339, MIM:613784

GenCC curated gene-disease

Mondo (3): susceptibility to HIV infection (MONDO:0004951), coronary heart disease, susceptibility to, 1 (MONDO:0011817), age related macular degeneration 12 (MONDO:0013420)

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST002337_103	Amyotrophic lateral sclerosis (sporadic)	7.000000e-06
GCST003075_110	Cognitive decline rate in late mild cognitive impairment	3.000000e-07
GCST003075_6	Cognitive decline rate in late mild cognitive impairment	5.000000e-08
GCST003518_42	Daytime sleep phenotypes	8.000000e-06
GCST004608_68	Granulocyte percentage of myeloid white cells	2.000000e-25
GCST004609_106	Monocyte percentage of white cells	1.000000e-24
GCST004625_64	Monocyte count	6.000000e-32
GCST004627_95	Lymphocyte count	5.000000e-10
GCST010571_17	Autoimmune thyroid disease	1.000000e-10
GCST90002388_192	Lymphocyte count	5.000000e-33
GCST90002389_14	Lymphocyte percentage of white cells	1.000000e-11
GCST90002393_401	Monocyte count	8.000000e-83
GCST90002394_232	Monocyte percentage of white cells	6.000000e-53
GCST90002399_134	Neutrophil percentage of white cells	9.000000e-20
GCST90002407_44	White blood cell count	3.000000e-14
GCST90013663_90	Alanine aminotransferase levels	1.000000e-09
GCST90013664_64	Aspartate aminotransferase levels	7.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0007828	daytime rest measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4843 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 87,042 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1201082	FLUOXETINE HYDROCHLORIDE	4	18,871
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL1722209	TOLTERODINE TARTRATE	4	3,920
CHEMBL2111101	PIMAVANSERIN	4	1,357
CHEMBL502182	ELAGOLIX SODIUM	4	214
CHEMBL567	PERPHENAZINE	4	21,883
CHEMBL2349310	AZD-8797	2	57
CHEMBL3039531	DANIRIXIN	2	357

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
[125I]CX3CL1 (human)	Full agonist	9.72	pKd
JMS-17-2	Antagonist	9.49	pIC50
CX3CL1	Full agonist	8.9	pIC50
rugocrixan	Antagonist	8.14	pKi
AZD0233	Antagonist	7.0	pEC50

Binding affinities (BindingDB)

33 measured of 41 human assays (41 total across all organisms); most potent 33 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(4-((R*)-2-(3-Chloro-2-fluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 2)	IC50	68 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2R)-2-(2,3-difluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	104 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-6-[(2R)-2-(2,3,4-trifluorophenyl)propyl]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	115 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2R)-2-(2-fluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	180 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2R)-2-(4-chloro-2-fluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	348 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((R*)-2-(3,4-Dichlorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 2)	IC50	362 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2S)-2-(4-chloro-2-fluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	424 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2S)-2-(2,3-difluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	430 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((S*)-2-(3-Chloro-2-fluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 1)	IC50	448 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2R)-2-(2-fluoro-4-methoxyphenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	470 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-6-[(2R)-2-phenylpropyl]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	484 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2S)-2-(2-fluoro-4-methoxyphenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	566 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2S)-2-(2-fluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	637 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((R)-2-(2-Chloropyridin-4-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide	IC50	682 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2R)-2-(2-fluoro-6-methoxy-3-pyridinyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	691 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-6-[(2R)-2-(6-methoxy-3-pyridinyl)propyl]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	886 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((S*)-2-(2,4-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 1)	IC50	895 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((R*)-2-(2,4-Difluorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide Isomer 2	IC50	948 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[2-(2-fluorophenyl)butyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	987 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2R)-2-(5-chloro-2-pyridinyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	1530 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-(2-(2-Ethoxypyridin-4-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide	IC50	1830 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((R*)-2-(2-Cyclopropylpyrimidin-5-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 2)	IC50	1860 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((S)-2-(3,4-Dichlorophenyl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide	IC50	1970 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2R)-2-(4-fluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	2470 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((R*)-2-(6-methoxy-5-methylpyridin-3-yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 1)	IC50	2990 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((R*)-2-(6-methoxy-4-methylpyridin-3-yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 1)	IC50	4250 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((R*)-2-(2-methoxypyridin-3-yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 1)	IC50	4370 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[(2S)-2-(4-fluorophenyl)propyl]-6-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	4900 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-[4-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-6-[(2S)-2-(6-methoxy-3-pyridinyl)propyl]-1,3,5-triazin-2-yl]methanesulfonamide	IC50	5180 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((R*)-2-(2,6-Dimethoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 1)	IC50	5520 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((S*)-2-(2,6-Dimethoxypyridin-3-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 2)	IC50	11000 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-((S*)-2-(2-Chloropyridin-4-yl)propyl)-6-(((R)-1-hydroxy-4-methylpentan-2-yl)amino)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 1)	IC50	13500 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1
N-(4-(((R)-1-Hydroxy-4-methylpentan-2-yl)amino)-6-((S*)-2-(2-methoxypyridin-3-yl)propyl)-1,3,5-triazin-2-yl)methanesulfonamide (Isomer 2)	IC50	16700 nM	WO-2024083933: 2,4,6-TRISUBSTITUTED 1,3,5-TRIAZINES AS MODULATORS OF CX 3CR1

ChEMBL bioactivities

82 potent at pChembl≥5 of 84 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.41	Ki	3.9	nM	AZD-8797
8.40	Ki	4	nM	CHEMBL2349322
8.40	IC50	4	nM	CHEMBL4518556
8.33	Ki	4.7	nM	CHEMBL2349316
8.30	IC50	5	nM	CHEMBL4539605
8.24	Ki	5.8	nM	CHEMBL2349180
8.22	IC50	6	nM	CHEMBL4577003
8.22	IC50	6	nM	CHEMBL4474066
8.21	Ki	6.2	nM	CHEMBL2349179
8.11	Ki	7.8	nM	CHEMBL2349312
8.10	Ki	8	nM	CHEMBL2349313
8.09	Ki	8.1	nM	CHEMBL2349332
8.08	Ki	8.3	nM	CHEMBL2349303
8.00	Ki	10	nM	CHEMBL2349306
7.96	IC50	11	nM	CHEMBL4475030
7.92	IC50	12	nM	CHEMBL4442967
7.89	Ki	13	nM	CHEMBL2349314
7.89	IC50	13	nM	CHEMBL4565523
7.85	Ki	14	nM	CHEMBL2349318
7.85	IC50	14	nM	CHEMBL4551880
7.80	IC50	16	nM	CHEMBL4435586
7.80	IC50	16	nM	CHEMBL4443425
7.75	Ki	18	nM	CHEMBL2349182
7.75	Ki	18	nM	CHEMBL2349311
7.68	Ki	21	nM	CHEMBL2349181
7.68	IC50	21	nM	CHEMBL4456446
7.64	Ki	23	nM	CHEMBL2349324
7.55	Ki	28	nM	CHEMBL2349319
7.52	Ki	30	nM	CHEMBL2349321
7.51	IC50	31	nM	CHEMBL4447653
7.50	Ki	32	nM	CHEMBL2349328
7.38	Ki	42	nM	CHEMBL2349317
7.37	Ki	43	nM	CHEMBL2349302
7.36	Ki	44	nM	CHEMBL2349186
7.33	Ki	47	nM	CHEMBL2349330
7.32	Ki	48	nM	CHEMBL2349335
7.29	Ki	51	nM	CHEMBL2349323
7.16	Ki	70	nM	CHEMBL2349325
7.15	Ki	71	nM	CHEMBL2349333
7.04	Ki	91	nM	CHEMBL2349301
7.04	Ki	91	nM	CHEMBL2349329
7.00	Ki	99	nM	CHEMBL2349327
7.00	Ki	100	nM	CHEMBL2349339
6.99	Ki	102	nM	CHEMBL2349315
6.96	Ki	110	nM	CHEMBL2349184
6.96	Ki	110	nM	CHEMBL2349183
6.92	Ki	120	nM	CHEMBL2349326
6.72	Ki	190	nM	CHEMBL2349320
6.66	Ki	220	nM	CHEMBL2349304
6.66	Ki	220	nM	CHEMBL2349337

PubChem BioAssay actives

51 with measured affinity, of 83 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
(2R)-2-[[2-amino-5-[(1S)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0039	uM
(2R)-2-[[2-amino-5-[(2-bromophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0040	uM
(2R)-2-[[2-amino-5-[(1S)-1-(2-fluorophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0047	uM
5-[(1S)-1-(4-chloro-2-pyridinyl)ethyl]sulfanyl-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0058	uM
(2R)-2-[[2-amino-5-[(1S)-1-(4-chloro-2-pyridinyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0062	uM
7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-5-[(1S)-1-phenylethyl]sulfanyl-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0078	uM
7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-5-[(1R)-1-phenylethyl]sulfanyl-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0080	uM
(2R)-2-[[2-amino-5-[(4-bromo-2-fluorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0081	uM
methyl (2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentanoate	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0083	uM
5-[(2,3-difluorophenyl)methylsulfanyl]-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0100	uM
(2R)-2-[[2-amino-5-[(1S)-1-(2-bromophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0130	uM
3-[(1S)-1-[[7-[[(2R)-1-hydroxypentan-2-yl]amino]-2-oxo-3H-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0140	uM
(2R)-2-[[2-amino-5-[(1R)-1-phenylethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0180	uM
(2R)-2-[[2-amino-5-(2-phenylethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0180	uM
5-[(1S)-1-(4-chloro-3-pyridinyl)ethyl]sulfanyl-7-[[(2R)-1-hydroxypentan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0210	uM
(2R)-2-[[2-amino-5-[(2-fluorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0230	uM
(2R)-2-[[2-amino-5-[(1S)-1-(3-methylsulfonylphenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0280	uM
5-benzylsulfanyl-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0300	uM
(2R)-2-[[2-amino-5-[(3-bromophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0320	uM
3-[(1S)-1-[[2-amino-7-[[(2R)-1-hydroxypentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanyl]ethyl]benzonitrile	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0420	uM
methyl (2R)-2-[[2-amino-5-[(2-chlorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentanoate	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0430	uM
7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-5-phenylmethoxy-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0440	uM
(2R)-2-[[2-amino-5-[(4-bromophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0470	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0480	uM
(2R)-2-[[2-amino-5-[(2-chlorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0510	uM
(2R)-2-[[2-amino-5-[(2-methylphenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0700	uM
(2R)-2-[[2-amino-5-[(2,3-difluorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0710	uM
3-[[2-amino-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanylmethyl]benzonitrile	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0910	uM
(3R)-3-[[2-amino-5-[(2-chlorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-5-methylhexan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0910	uM
(2R)-2-[[2-amino-5-[(2-methoxyphenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.0990	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]pentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.1000	uM
(2R)-2-[[2-amino-5-[(1R)-1-(2-bromophenyl)ethyl]sulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.1020	uM
5-benzylsulfonyl-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.1100	uM
(2R)-2-[[2-amino-5-(3-phenylpropylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.1100	uM
2-[[2-amino-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanylmethyl]benzonitrile	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.1200	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-3,3-dimethylbutan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.1900	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentanamide	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.2200	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-2-phenylethanol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.2200	uM
5-benzylsulfinyl-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.2800	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentanoic acid	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.3200	uM
(2R)-2-[[2-amino-5-(pyridin-2-ylmethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.3600	uM
5-benzylsulfanyl-7-[[(2R)-1-hydroxybutan-2-yl]amino]-3H-[1,3]thiazolo[4,5-d]pyrimidin-2-one	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.5600	uM
(2S)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.6000	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-3-methylbutan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.6400	uM
(2R)-2-[[2-amino-5-(pyridin-3-ylmethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.6700	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]butan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.7700	uM
(2R)-2-[[2-amino-5-(pyridin-4-ylmethylsulfanyl)-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	0.9000	uM
(2R)-2-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]propan-1-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	1.1000	uM
(3R)-3-[(2-amino-5-benzylsulfanyl-[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-2,5-dimethylhexan-2-ol	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	1.2000	uM
4-[[2-amino-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-[1,3]thiazolo[4,5-d]pyrimidin-5-yl]sulfanylmethyl]benzonitrile	740906: Displacement of [125I]-CX3CL1 from human CX3CR1 transfected in HEK293 cells after 24 hrs by scintillation counting analysis	ki	1.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Nickel	decreases expression, increases expression	2
Ozone	affects expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenite	affects methylation	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
vanadium pentoxide	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
GW 501516	decreases expression	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
perfluorobutanesulfonic acid	decreases expression	1
incobotulinumtoxinA	increases expression	1
Rosiglitazone	affects localization, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Hexachlorocyclohexane	decreases expression	1
Cadmium	decreases expression	1
Choline	affects expression	1
Diazinon	decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1

ChEMBL screening assays

26 unique, capped per target: 19 binding, 7 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003797	Binding	Displacement of [125I]fractalkine from human CX2CR1 expressed in CHO cells at 10 uM	Synthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists. — Bioorg Med Chem Lett
CHEMBL2328507	Functional	Antagonist activity at CX3CR1 (unknown origin) assessed as inhibition of calcium flux at 10 uM	1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 4 spontaneously immortalized cell line, 2 cancer cell line, 1 undefined cell line type

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

Cellosaurus	Name	Category	Sex
CVCL_1E09	GHOST(3).V28/CX3CR1	Cancer cell line	Female
CVCL_B9XI	Abcam THP-1 CX3CR1 KO	Cancer cell line	Male
CVCL_KS82	Chem-4 CX3CR1	Undefined cell line type
CVCL_KW64	PathHunter CHO-K1 CCRL1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KW77	PathHunter CHO-K1 CX3CR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_RP99	ValiScreen human CX3CR1	Spontaneously immortalized cell line	Female
CVCL_RQ21	CHO-K1 (+Galpha16) AequoScreen CX3CR1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05945394	Not specified	UNKNOWN	The Surem TRAF3IP2 Level and Atherosclerotic Plaque Development in Human