Protein / target
C-X-C chemokine receptor type 4
Protein at a glance
Biological role
C-X-C motif chemokine 12 receptor activity
Primary system
Nervous system
Strongest disease association
WHIM syndrome
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 5 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:10074102, PubMed:10452968, PubMed:10644702, PubMed:10825158, PubMed:18799424, PubMed:20048153, PubMed:20505072, PubMed:24912431, PubMed:28978524, PubMed:8752280, PubMed:8752281). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:16725153, PubMed:17197449, PubMed:18799424, PubMed:39093700). CXCR4 is coupled to G(i) G alpha proteins and mediates inhibition of adenylate cyclase (PubMed:17197449, PubMed:39093700). Involved in the AKT signaling cascade (PubMed:24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed:28978524). Also acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed:20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Involved in hematopoiesis and in cardiac ventricular septum formation (By similarity). Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells (By similarity). Involved in cerebellar development; in the CNS, could mediate hippocampal-neuron surviva (By similarity)
Subcellular location
Domains and Gene Ontology detail (45)Hide
Gene Ontology
- Canchoring junction
- Ccell leading edge
- Ccell surface
- Ccytoplasm
- Ccytoplasmic vesicle
- Cearly endosome
- Cexternal side of plasma membrane
- Cextracellular exosome
- Clate endosome
- Clysosome
- Cplasma membrane
- Cprotein-containing complex
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing int…
- ·cellular response to cytokine stimulus
- ·immune response
- ·inflammatory response
Cell adhesion
- ·Cell junction
- ·regulation of cell adhesion
G protein-coupled signalling
- ·G protein-coupled receptor activity
- ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- ·G protein-coupled receptor signaling pathway
Apoptosis & cell death
- ·apoptotic process
Muscle contraction
- ·myosin light chain binding
View underlying pathways (7)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
C-X-C chemokine receptor type 4 partial agonist
Appears in clinical studies involving acute lymphoblastic leukemia, plasma cell myeloma, non-Hodgkin lymphoma, non-Hodgkin lymphoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 2,464 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 8 total
macular degeneration · Hodgkins lymphoma · non-Hodgkin lymphoma
inborn error of immunity · neoplasm · WHIM syndrome
acute lymphoblastic leukemia · plasma cell myeloma · non-Hodgkin lymphoma
neoplasm
plasma cell myeloma · neoplasm · acute myeloid leukemia by FAB classification
breast cancer · plasma cell myeloma · ST Elevation Myocardial Infarction
sarcoma
plasma cell myeloma · acute myeloid leukemia · malignant pancreatic neoplasm
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
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 underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationA phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome.
- Regulatory approval
Approval: Plerixafor Accord (EMA)
- Regulatory approval
Approval: Mozobil (EMA)
- New publicationRapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.