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GeneE
50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CXCL12
C-X-C motif chemokine ligand 12
Chromosome 10 · 10q11.21
NCBI Gene: 6387Ensembl: ENSG00000107562.18HGNC: HGNC:10672UniProt: P48061
1,470PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of cell adhesionpositive regulation of T cell migrationintegrin bindingprotein bindingHIV-1 infectioncoronary artery diseaseresponse to reverse transcriptase inhibitormyocardial infarction
✦AI Summary

CXCL12 is a homeostatic chemokine that functions primarily through binding to receptors CXCR4 and CXCR7 to regulate cell migration and activation 1. In normal physiology, CXCL12 induces migration and activation of hematopoietic progenitor cells, endothelial cells, and leukocytes, playing essential roles in embryogenesis, hematopoiesis, and angiogenesis 1. The chemokine exhibits context-dependent activity: at lower concentrations it acts as a chemoattractant for lymphocytes, while higher concentrations may produce chemorepellent effects 2. CXCL12 can be regulated through interaction with cell surface proteoglycans and post-translational modifications that preserve local activity 3. In disease contexts, CXCL12-CXCR4/CXCR7 signaling promotes tumor cell proliferation, survival, angiogenesis, and metastasis across multiple cancer types including leukemia, breast cancer, lung cancer, and pancreatic cancer 4. Binding to CXCR4 activates pro-survival pathways including PI3K/mTOR and MEK/ERK, while CXCR7 engagement triggers β-arrestin signaling 2. The axis also contributes to fibrotic disease pathology through effects on inflammation, immunity, and epithelial-mesenchymal transition 5. Recent evidence indicates CXCL12 participates in androgenic alopecia, with androgen-induced CXCL12 expression in human hair follicle cells contributing to hair miniaturization 6. CXCL12-CXCR4/CXCR7 represents a promising biomarker and therapeutic target, with CXCR4 antagonists like Plerixafor currently in clinical trials 2.

Sources cited
1
CXCL12 is a homeostatic chemokine inducing migration/activation of hematopoietic progenitor cells, endothelial cells, and leukocytes through CXCR4 and CXCR7; essential for embryogenesis, hematopoiesis, and angiogenesis
PMID: 36725964
2
CXCL12 binding to cell surface proteoglycans inhibits formation of inactive SDF-1-alpha(3-67) and preserves activity on local sites
PMID: 14525775
3
CXCL12-CXCR4/CXCR7 signaling promotes tumor cell proliferation, survival, angiogenesis, and metastasis in leukemia, breast cancer, lung cancer, prostate cancer, and multiple myeloma
PMID: 37497001
4
CXCL12 binding to CXCR4 activates PI3K/mTOR and MEK/ERK signaling; binding to CXCR7 activates β-arrestin signaling; exhibits dual chemoattractant/chemorepellant properties based on concentration
PMID: 31874281
5
CXCL12/CXCR4 contributes to fibrosis pathology through effects on inflammation, immunity, epithelial-mesenchymal transition, and angiogenesis
PMID: 36442720
6
Androgen-induced CXCL12 expression in human dermal papilla and dermal sheath cup cells contributes to hair miniaturization in androgenic alopecia
PMID: 39795953
Disease Associationsⓘ20
HIV-1 infectionOpen Targets
0.37Weak
coronary artery diseaseOpen Targets
0.36Weak
response to reverse transcriptase inhibitorOpen Targets
0.36Weak
myocardial infarctionOpen Targets
0.34Weak
secondary malignant neoplasmOpen Targets
0.34Weak
pernicious anemiaOpen Targets
0.33Weak
biliary tract diseaseOpen Targets
0.32Weak
coronary atherosclerosisOpen Targets
0.32Weak
Herpes ZosterOpen Targets
0.32Weak
nervous system diseaseOpen Targets
0.31Weak
complicationOpen Targets
0.31Weak
Myocardial IschemiaOpen Targets
0.31Weak
adolescent idiopathic scoliosisOpen Targets
0.29Weak
Abnormal pupillary functionOpen Targets
0.29Weak
angina pectorisOpen Targets
0.27Weak
Abruptio PlacentaeOpen Targets
0.26Weak
cervical carcinomaOpen Targets
0.26Weak
heart diseaseOpen Targets
0.25Weak
intermediate coronary syndromeOpen Targets
0.25Weak
chronic hepatitisOpen Targets
0.23Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCR2Protein interaction100%PPBPProtein interaction100%CCL28Protein interaction100%CXCL14Protein interaction100%CXCL17Protein interaction100%XCL2Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Liver
95%
Bone Marrow
51%
Ovary
35%
Lung
23%
Brain
5%
Gene Interaction Network
Click a node to explore
CXCL12CCR2PPBPCCL28CXCL14CXCL17XCL2
PROTEIN STRUCTURE
Preparing viewer…
PDB3GV3 · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.47 [0.23–1.07]
RankingsWhere CXCL12 stands among ~20K protein-coding genes
  • #89of 20,598
    Most Researched1,470 · top 1%
  • #10,754of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedCXCL12
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.
PMID: 37497001
Int J Biol Sci · 2023
1.00
2
The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
PMID: 36725964
Cell Mol Immunol · 2023
0.90
3
Synergy by Ristocetin and CXCL12 in Human Platelet Activation: Divergent Regulation by Rho/Rho-Kinase and Rac.
PMID: 37298667
Int J Mol Sci · 2023
0.86
4
CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma.
PMID: 36300800
Cancer Med · 2023
0.84
5
CXCL12 Gene Polymorphisms and Serum Levels: Associations with Multiple Sclerosis Prevalence and Clinical Parameters in Lithuania.
PMID: 39273501
Int J Mol Sci · 2024
0.82