CX3CL1 Gene

HGNC Family	Endogenous ligands, Chemokine ligands (CCL)
Name	chemokine (C-X3-C motif) ligand 1
Description	This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fractalkine (CX3CL1) is a unique chemokine that functions dually as both a soluble chemoattractant and a membrane‐bound adhesion molecule. It is expressed by a variety of cell types – including endothelial and smooth muscle cells, neurons, and epithelial cells – and plays a central role in mediating leukocyte trafficking, cell survival, and intercellular communication under both homeostatic and inflammatory conditions. For example, in vascular inflammation and atherosclerosis, CX3CL1 produced by lesional smooth muscle cells recruits circulating monocytes and supports their survival, thereby contributing to foam cell formation and lesion progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Similarly, CX3CL1 directs the migration of cytotoxic effector lymphocytes – including natural killer cells and CD8⁺ T cells – by capturing them from blood flow and enhancing their response to secondary chemokine signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, the chemokine is rapidly released from apoptotic cells to attract macrophages for efficient clearance of dying cells, thereby contributing to tissue remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " A comprehensive review of fractalkine’s functions emphasizes its dual adhesive and chemotactic properties, which impact diverse immunopathological states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond the vasculature, CX3CL1 also plays a critical role in tissue repair and regeneration. In skin wound healing, for instance, fractalkine expressed on macrophages and endothelial cells mediates the recruitment of bone marrow–derived monocytes that secrete profibrotic and angiogenic mediators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In the developing central nervous system, neuronal CX3CL1 regulates microglial recruitment and activation, thereby influencing synaptic pruning and the maturation of glutamatergic circuits; this mechanism is also implicated in neurodegenerative pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Structural insights have further revealed that CX3CL1 interacts intimately with receptor sites – as exemplified by its binding to the cytomegalovirus GPCR US28 – underscoring its conserved mode of receptor activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In pulmonary arterial hypertension, endothelial-derived CX3CL1 contributes to the recruitment and activation of T lymphocytes, thereby participating in the inflammatory milieu of the diseased vasculature."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Similarly, in chronic liver injury, fractalkine produced by hepatocytes and hepatic stellate cells modulates the survival and differentiation of infiltrating macrophages, ultimately limiting fibrogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings demonstrate that CX3CL1 acts as a pivotal mediator in diverse biological contexts by orchestrating immune cell recruitment, ensuring the survival of mononuclear phagocytes, and facilitating crucial cell–cell interactions. Its multifaceted roles make the CX3CL1/CX3CR1 signaling axis a promising therapeutic target in inflammatory, neurodegenerative, and cardiovascular diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Philippe Lesnik, Christopher A Haskell, Israel F Charo "}, {"type": "b", "children": [{"type": "t", "text": "Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine in atherogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI15555"}], "href": "https://doi.org/10.1172/JCI15555"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12569158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12569158"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Limor Landsman, Liat Bar-On, Alma Zernecke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-07-170787"}], "href": "https://doi.org/10.1182/blood-2008-07-170787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18971423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18971423"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sherine Ensan, Angela Li, Rickvinder Besla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni.3343"}], "href": "https://doi.org/10.1038/ni.3343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26642357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26642357"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Miyuki Nishimura, Hisanori Umehara, Takashi Nakayama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual functions of fractalkine/CX3C ligand 1 in trafficking of perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by CX3CR1 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.168.12.6173"}], "href": "https://doi.org/10.4049/jimmunol.168.12.6173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12055230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12055230"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lucy A Truman, Catriona A Ford, Marta Pasikowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-06-162404"}], "href": "https://doi.org/10.1182/blood-2008-06-162404"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18799722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18799722"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hisanori Umehara, Eda T Bloom, Toshiro Okazaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fractalkine in vascular biology: from basic research to clinical disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000095360.62479.1F"}], "href": "https://doi.org/10.1161/01.ATV.0000095360.62479.1F"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12969992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12969992"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shih-Chieh Hung, Radhika R Pochampally, Shu-Ching Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0000416"}], "href": "https://doi.org/10.1371/journal.pone.0000416"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17476338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17476338"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Maki Hoshiko, Isabelle Arnoux, Elena Avignone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1167-12.2012"}], "href": "https://doi.org/10.1523/JNEUROSCI.1167-12.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23100431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23100431"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Paula Marie Hughes, Michelle Sandra Botham, Stefan Frentzel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11870871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11870871"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "John S Burg, Jessica R Ingram, A J Venkatakrishnan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aaa5026"}], "href": "https://doi.org/10.1126/science.aaa5026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25745166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25745166"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Karl Balabanian, Arnaud Foussat, Peter Dorfmüller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CX(3)C chemokine fractalkine in pulmonary arterial hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Crit Care Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1164/rccm.2106007"}], "href": "https://doi.org/10.1164/rccm.2106007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12016106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12016106"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Karlin Raja Karlmark, Henning W Zimmermann, Christoph Roderburg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The fractalkine receptor CX₃CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.23894"}], "href": "https://doi.org/10.1002/hep.23894"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21038415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21038415"}]}]}]}
Synonyms	CXC3C, ABCD-3, FRACTALKINE, C3XKINE, NTT, SCYD1, NEUROTACTIN, CXC3
Proteins	X3CL1_HUMAN
NCBI Gene ID	6376
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CX3CL1 has 9,596 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 113 datasets.

Click the + buttons to view associations for CX3CL1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CX3CL1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CX3CL1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CX3CL1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CX3CL1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CX3CL1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CX3CL1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CX3CL1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CX3CL1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CX3CL1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CX3CL1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CX3CL1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CX3CL1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CX3CL1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CX3CL1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CX3CL1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CX3CL1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CX3CL1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing CX3CL1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CX3CL1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CX3CL1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CX3CL1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CX3CL1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CX3CL1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CX3CL1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CX3CL1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CX3CL1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CX3CL1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CX3CL1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CX3CL1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CX3CL1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CX3CL1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CX3CL1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CX3CL1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CX3CL1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CX3CL1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CX3CL1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CX3CL1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CX3CL1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CX3CL1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CX3CL1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of CX3CL1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.