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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ACKR2
atypical chemokine receptor 2
Chromosome 3 · 3p22.1
NCBI Gene: 1238Ensembl: ENSG00000144648.17HGNC: HGNC:1565UniProt: O00590
67PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
chemokine receptor activitycytosolprotein bindingactin filamentIntrahepatic cholestasis of pregnancyAlzheimer diseaseliver diseaseneoplasm
✦AI Summary

ACKR2 (atypical chemokine receptor 2) is a specialized chemokine scavenger that regulates inflammatory responses by binding and degrading CC chemokines without triggering conventional G-protein signaling cascades 1. The receptor is expressed in various cell types including lymphatic endothelial cells, trophoblasts, and lung capillary endothelial cells (aerocytes) 2. ACKR2 functions by sequestering inflammatory chemokines like CCL5 and CXCL10, thereby modulating immune cell recruitment and tissue inflammation 3. In reproductive biology, ACKR2 in trophoblasts protects against inflammation-induced pregnancy complications and is essential for normal placental development and fetal survival 4. In cancer, ACKR2 exhibits context-dependent roles: it can promote tumor progression by inducing CD8+ T cell senescence in cervical cancer after chemoradiotherapy 5, facilitate lung cancer metastasis through CXCL14-dependent signaling 6, yet also suppress lung metastases by regulating T lymphocyte extravasation 2. Clinically, ACKR2 expression serves as a prognostic biomarker in various cancers, with therapeutic targeting showing promise for enhancing immunotherapy responses, particularly in 'cold' tumors resistant to immune checkpoint blockade 3.

Sources cited
1
ACKR2 is a chemokine scavenger that binds CC chemokines and affects inflammatory microenvironments
PMID: 35677043
2
ACKR2 is expressed in lymphatic endothelial cells and lung capillary endothelial cells (aerocytes)
PMID: 39843164
3
ACKR2 sequesters chemokines like CCL5 and CXCL10 and modulates immune cell recruitment
PMID: 40248897
4
ACKR2 in trophoblasts protects against pregnancy complications and is essential for placental development
PMID: 25297873
5
ACKR2 promotes CD8+ T cell senescence in cervical cancer after chemoradiotherapy
PMID: 38723624
6
ACKR2 facilitates lung cancer metastasis through CXCL14-dependent signaling
PMID: 37056937
7
ACKR2 suppresses lung metastases by regulating T lymphocyte extravasation
PMID: 39843164
8
ACKR2 targeting shows promise for enhancing immunotherapy responses
PMID: 40248897
Disease Associationsⓘ20
Intrahepatic cholestasis of pregnancyOpen Targets
0.16Weak
Alzheimer diseaseOpen Targets
0.16Weak
liver diseaseOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
cholestasis, intrahepatic, of pregnancy 3Open Targets
0.10Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.09Suggestive
cervical carcinomaOpen Targets
0.07Suggestive
acne inversa, familial, 3Open Targets
0.07Suggestive
kidney diseaseOpen Targets
0.06Suggestive
dermatomycosisOpen Targets
0.06Suggestive
cervical cancerOpen Targets
0.06Suggestive
psoriasisOpen Targets
0.06Suggestive
psoriatic arthritisOpen Targets
0.06Suggestive
melanomaOpen Targets
0.06Suggestive
uterine cervix neoplasmOpen Targets
0.06Suggestive
lung cancerOpen Targets
0.06Suggestive
lupus nephritisOpen Targets
0.05Suggestive
acne inversa, familial, 1Open Targets
0.05Suggestive
chilblain lupus 2Open Targets
0.05Suggestive
X-linked intellectual disability-seizures-psoriasis syndromeOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CD8AProtein interaction100%CCL8Protein interaction100%CCL28Protein interaction100%CCL14Protein interaction99%ACKR1Protein interaction99%CCL3L3Protein interaction99%
Tissue Expression6 tissues
Liver
100%
Lung
14%
Brain
10%
Heart
8%
Bone Marrow
7%
Ovary
4%
Gene Interaction Network
Click a node to explore
ACKR2CD8ACCL8CCL28CCL14ACKR1CCL3L3
PROTEIN STRUCTURE
Preparing viewer…
PDB8J8V · 3.22 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.93LoF Tolerant
pLIⓘ
0.12Tolerant
Observed/Expected LoF2.63 [0.36–1.93]
RankingsWhere ACKR2 stands among ~20K protein-coding genes
  • #6,962of 20,598
    Most Researched67
  • #17,515of 17,882
    Most Constrained (LOEUF)1.93
Genes detectedACKR2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Chemoradiotherapy-induced ACKR2
PMID: 38723624
Cell Rep Med · 2024
1.00
2
CXCL14 promotes metastasis of non-small cell lung cancer through ACKR2-depended signaling pathway.
PMID: 37056937
Int J Biol Sci · 2023
0.90
3
Selective expression and significance of ACKR2 in lung aerocytes.
PMID: 39843164
J Immunother Cancer · 2025
0.80
4
The Role of Atypical Chemokine Receptor D6 (ACKR2) in Physiological and Pathological Conditions; Friend, Foe, or Both?
PMID: 35677043
Front Immunol · 2022
0.70
5
Atypical chemokine receptors in cancer.
PMID: 38266462
Cytokine · 2024
0.60