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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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XCL2
X-C motif chemokine ligand 2
Chromosome 1 · 1q24.2
NCBI Gene: 6846Ensembl: ENSG00000143185.4HGNC: HGNC:10646UniProt: Q9UBD3
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingchemokine activityCCR chemokine receptor bindinginflammatory responsepsoriasisneurodegenerative diseasebasal cell carcinomalung cancer
✦AI Summary

XCL2 (X-C motif chemokine ligand 2) is a chemokine that functions primarily in immune cell recruitment and activation, particularly targeting lymphocytes rather than monocytes or neutrophils 1. The protein exhibits a unique metamorphic structure, exchanging between monomeric and dimeric forms under physiological conditions, with the monomeric form responsible for G protein-coupled receptor activation and the dimeric form important for glycosaminoglycan binding 1. XCL2 plays a critical role in tumor immunity by facilitating recruitment of conventional type 1 dendritic cells (cDC1) into the tumor microenvironment, where it correlates with NK cell gene signatures and improved patient survival 2. The chemokine supports tissue-resident memory T cell formation and positioning, with enforced expression promoting intratumoral cDC1 accumulation and enhanced T cell persistence, leading to improved tumor control 3. XCL2 expression is generally downregulated in tumor tissues and correlates with cancer prognosis, DNA methylation status, and immune cell infiltration patterns 4. Additionally, XCL2 has been implicated in various disease contexts, including serving as a potential diagnostic marker in Parkinson's disease progression through its specific expression in NK cell subclusters 5, and showing associations with bronchiectasis risk through DNA methylation-mediated mechanisms 6.

Sources cited
1
XCL2 exhibits metamorphic structure and lymphocyte-specific chemotactic activity
PMID: 25497737
2
XCL2 facilitates cDC1 recruitment in tumor microenvironment and correlates with patient survival
PMID: 29429633
3
XCL2 supports tissue-resident memory T cell formation and tumor control
PMID: 39841133
4
XCL2 expression is downregulated in tumors and correlates with cancer prognosis and immune infiltration
PMID: 37905956
5
XCL2 serves as potential diagnostic marker in Parkinson's disease through NK cell expression
PMID: 39366969
6
XCL2 shows associations with bronchiectasis risk through DNA methylation mechanisms
PMID: 40536885
Disease Associationsⓘ20
psoriasisOpen Targets
0.40Weak
neurodegenerative diseaseOpen Targets
0.39Weak
basal cell carcinomaOpen Targets
0.39Weak
lung cancerOpen Targets
0.34Weak
non-melanoma skin carcinomaOpen Targets
0.31Weak
hypothyroidismOpen Targets
0.31Weak
Hashimoto's thyroiditisOpen Targets
0.30Weak
skin cancerOpen Targets
0.30Weak
polypOpen Targets
0.15Weak
body weight gainOpen Targets
0.15Weak
blood coagulation diseaseOpen Targets
0.15Weak
ThromboembolismOpen Targets
0.14Weak
thrombophiliaOpen Targets
0.12Weak
gestational diabetesOpen Targets
0.10Suggestive
cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
myeloid leukemiaOpen Targets
0.07Suggestive
HepatitisOpen Targets
0.06Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.05Suggestive
systemic lupus erythematosusOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
XCR1Protein interaction100%CXCR3Protein interaction100%PF4Protein interaction100%PF4V1Protein interaction100%CCL21Protein interaction100%CXCL12Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
18%
Lung
16%
Brain
1%
Ovary
1%
Heart
0%
Gene Interaction Network
Click a node to explore
XCL2XCR1CXCR3PF4PF4V1CCL21CXCL12
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UBD3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.66LoF Tolerant
pLIⓘ
0.02Tolerant
Observed/Expected LoF0.83 [0.43–1.66]
RankingsWhere XCL2 stands among ~20K protein-coding genes
  • #13,800of 20,598
    Most Researched22
  • #15,936of 17,882
    Most Constrained (LOEUF)1.66
Genes detectedXCL2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control.
PMID: 29429633
Cell · 2018
1.00
2
Single-cell RNA sequencing reveals peripheral immunological features in Parkinson's Disease.
PMID: 39366969
NPJ Parkinsons Dis · 2024
0.90
3
The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.
PMID: 39841133
J Exp Med · 2025
0.80
4
Comprehensive analysis reveals XCL2 as a cancer prognosis and immune infiltration-related biomarker.
PMID: 37905956
Aging (Albany NY) · 2023
0.70
5
Structural and agonist properties of XCL2, the other member of the C-chemokine subfamily.
PMID: 25497737
Cytokine · 2015
0.60