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Protein / target

CX3C chemokine receptor 1

Encoded byCX3CR1P49238Homo sapiensSwiss-Prot
Small-molecule tractable
Druggability
Structure with Ligand
3
Research papers

Protein at a glance

Biological role

G protein-coupled peptide receptor

Strongest disease association

Hypothyroidism

Via encoding gene CX3CR1 · Genetic evidence · score 0.80

Research activity

Emerging research

3 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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 (PubMed:12055230, PubMed:23125415, PubMed:9390561, PubMed:9782118). CX3CR1-CX3CL1 signaling mediates cell migratory functions (By similarity). Responsible for the recruitment of natural killer (NK) cells to inflamed tissues (By similarity). Acts as a regulator of inflammation process leading to atherogenesis by mediating macrophage and monocyte recruitment to inflamed atherosclerotic plaques, promoting cell survival (By similarity). Involved in airway inflammation by promoting interleukin 2-producing T helper (Th2) cell survival in inflamed lung (By similarity). Involved in the migration of circulating monocytes to non-inflamed tissues, where they differentiate into macrophages and dendritic cells (By similarity). Acts as a negative regulator of angiogenesis, probably by promoting macrophage chemotaxis (PubMed:14581400, PubMed:18971423). Plays a key role in brain microglia by regulating inflammatory response in the central nervous system (CNS) and regulating synapse maturation (By similarity). Required to restrain the microglial inflammatory response in the CNS and the resulting parenchymal damage in response to pathological stimuli (By similarity). Involved in brain development by participating in synaptic pruning, a natural process during which brain microglia eliminates extra synapses during postnatal development (By similarity). Synaptic pruning by microglia is required to promote the maturation of circuit connectivity during brain development (By similarity). Acts as an important regulator of the gut microbiota by controlling immunity to intestinal bacteria and fungi (By similarity). 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 (By similarity). 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 (PubMed:29326275). Also acts as a receptor for C-C motif chemokine CCL26, inducing cell chemotaxis (PubMed:20974991)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (58)

Gene Ontology

  • Ccell surface
  • Cdendritic tree
  • Cexternal side of plasma membrane
  • Cmacropinosome membrane
  • Cneuron projection
  • Cneuronal cell body membrane
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • FC-C chemokine binding
  • FC-C chemokine receptor activity
  • FC-X3-C chemokine binding
  • FC-X3-C chemokine receptor activity

355 aa · 40 kDa · 4 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GOCell migrationUniProt · GOCell proliferation & survivalUniProtImmune signallingUniProt · GOCell adhesionUniProt · GOG protein-coupled signallingGO
View supporting evidence

Synaptic signalling

  • ·Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte c…
  • ·modulation of chemical synaptic transmission
  • ·multiple spine synapse organization, single dendrite
  • ·synapse maturation

Cell migration

  • ·Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte c…
  • ·cell chemotaxis
  • ·chemotaxis
  • ·leukocyte chemotaxis

Cell proliferation & survival

  • ·Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte c…

Immune signalling

  • ·Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte c…
  • ·adaptive immune response
  • ·antifungal innate immune response
  • ·immune response

Cell adhesion

  • ·Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte c…
  • ·cell adhesion

G protein-coupled signalling

  • ·G protein-coupled peptide receptor activity
  • ·G protein-coupled receptor activity
  • ·G protein-coupled receptor signaling pathway
  • ·phospholipase C-activating G protein-coupled receptor signaling pathway

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CX3CR1

Gene-level evidence surfaced through the gene CX3CR1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Hypothyroidism
0.80Well supported

Genetic evidence dominant · Open Targets 0.49

Macular Degeneration
0.68Moderately supported

Genetic literature evidence dominant · Open Targets 0.40

Thyroid Diseases
0.53Moderately supported

Genetic evidence dominant · Open Targets 0.32

Thyroiditis, Autoimmune
0.44Limited support

Genetic evidence dominant · Open Targets 0.27

Retinitis Pigmentosa
0.39Preliminary

Animal model evidence dominant · Open Targets 0.12 · no direct causal or clinical evidence

View evidence synthesis (5)
HypothyroidismWell supported
0.80
agreement 0.680.92
Genetic100%

Open Targets aggregate 0.49 · 1 independent evidence family

Macular DegenerationModerately supported
0.68
agreement 0.550.81
Genetic literature55%Animal model37%Literature9%

Open Targets aggregate 0.40 · 3 independent evidence families

Thyroid DiseasesModerately supported
0.53
agreement 0.410.65
Genetic100%

Open Targets aggregate 0.32 · 1 independent evidence family

Thyroiditis, AutoimmuneLimited support
0.44
agreement 0.320.56
Genetic100%

Open Targets aggregate 0.27 · 1 independent evidence family

Retinitis PigmentosaPreliminary
0.39
agreement 0.210.56
Animal model97%Literature3%

Open Targets aggregate 0.12 · 2 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Hypothyroidism0.49
Macular Degeneration0.40
Thyroid Diseases0.32
Thyroiditis, Autoimmune0.27
Alcohol drinking0.16
Neoplasms0.12
Retinitis Pigmentosa0.12

Tractability

Small moleculesEmerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

3 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.