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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCR6
C-C motif chemokine receptor 6
Chromosome 6 · 6q27
NCBI Gene: 1235Ensembl: ENSG00000112486.19HGNC: HGNC:1607UniProt: P51684
210PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneReceptor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
C-C chemokine receptor activitysperm midpiecesperm principal piecesperm plasma membranerheumatoid arthritisneurodegenerative diseaseACPA-positive rheumatoid arthritisprimary biliary cirrhosis
✦AI Summary

CCR6 is a C-C chemokine receptor primarily functioning as a ligand-binding receptor for CCL20, the only known high-affinity chemokine ligand 1. Upon CCL20 binding, CCR6 transduces signals through increased intracellular calcium and cAMP levels 23. Beyond chemokines, CCR6 also binds non-chemokine ligands including β-defensins (DEFB1, DEFB4, DEFB4A/B), which activate similar signaling pathways and regulate sperm motility 34. CCR6 is expressed on B cells, dendritic cells, innate lymphoid cells, regulatory T cells, and Th17 cells, mediating their chemotaxis to inflammatory sites 1. It plays critical roles in immune homeostasis and responses at mucosal surfaces, including recruitment of both pro-inflammatory Th17 and anti-inflammatory Treg cells to intestinal tissues and other inflammation sites 5. CCR6-CCL20 axis dysregulation is implicated in multiple autoimmune and malignant diseases. Genome-wide association studies demonstrate strong correlations between CCR6 expression and severity in inflammatory bowel disease, psoriasis, rheumatoid arthritis, and multiple sclerosis 1. In cancer contexts, CCR6+ cell infiltration supports tumor immunosuppression through Treg recruitment in hepatocellular carcinoma 6 and represents a dysfunctional T cell population in lung adenocarcinoma 7. Blocking CCR6-CCL20 interactions therapeutically reduces disease severity across autoimmune conditions 1.

Sources cited
1
CCR6 expression on immune cell subsets (B cells, dendritic cells, Th17, Tregs); CCL20 as high-affinity ligand; GWAS correlations with IBD, psoriasis, RA, MS disease severity; therapeutic targeting reduces disease
PMID: 33971346
2
CCL20 binding to CCR6 increases intracellular calcium; CCR6 binds defensins DEFB4 and DEFB4A/B mediating chemotactic effects
PMID: 20068036
3
CCR6 binds non-chemokine ligands β-defensins in addition to CCL20; β-defensins can activate CCR6-expressing cells
PMID: 25585877
4
CCR6 binding to DEFB1 increases intracellular calcium and cAMP; essential for DEFB1 regulation of sperm motility and bactericidal activity
PMID: 25122636
5
CCR6-CCL20 pair responsible for chemotaxis of dendritic cells and T/B cells; essential for immune responses to microbes in intestinal mucosa and inflammatory modulation
PMID: 21376174
6
In hepatocellular carcinoma, CCL20 secretion from lipid droplet-laden macrophages recruits CCR6+ Tregs supporting immunosuppression and tumor progression
PMID: 38942796
7
CCR6+ TCF1+ cells represent dysfunctional T cell subset in lung adenocarcinoma lacking preferential benefit from immune checkpoint blockade
PMID: 34534464
Disease Associationsⓘ20
rheumatoid arthritisOpen Targets
0.53Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
ACPA-positive rheumatoid arthritisOpen Targets
0.36Weak
primary biliary cirrhosisOpen Targets
0.36Weak
skin cancerOpen Targets
0.30Weak
placenta praeviaOpen Targets
0.29Weak
skin neoplasmOpen Targets
0.27Weak
viral eye infectionOpen Targets
0.26Weak
cutaneous melanomaOpen Targets
0.24Weak
neoplasmOpen Targets
0.12Weak
experimental autoimmune encephalomyelitisOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.11Weak
psoriasisOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
systemic lupus erythematosusOpen Targets
0.10Suggestive
infectionOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.09Suggestive
asthmaOpen Targets
0.09Suggestive
systemic sclerodermaOpen Targets
0.09Suggestive
arthritisOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCL8Protein interaction100%DEFB4BProtein interaction100%CXCL14Protein interaction100%CCL3L1Protein interaction100%CCL13Protein interaction100%CCL15Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
27%
Brain
8%
Liver
5%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
CCR6CCL8DEFB4BCXCL14CCL3L1CCL13CCL15
PROTEIN STRUCTURE
Preparing viewer…
PDB6WWZ · 3.34 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.54LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.52 [0.21–1.54]
RankingsWhere CCR6 stands among ~20K protein-coding genes
  • #1,985of 20,598
    Most Researched210 · top 10%
  • #15,388of 17,882
    Most Constrained (LOEUF)1.54
Genes detectedCCR6
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
CCR6-CCL20 axis as a therapeutic target for autoimmune diseases.
PMID: 33971346
Autoimmun Rev · 2021
1.00
2
Lipid droplet accumulation mediates macrophage survival and Treg recruitment via the CCL20/CCR6 axis in human hepatocellular carcinoma.
PMID: 38942796
Cell Mol Immunol · 2024
0.90
3
Antigen dominance hierarchies shape TCF1
PMID: 34534464
Cell · 2021
0.80
4
Interleukin-17A and Keratinocytes in Psoriasis.
PMID: 32070069
Int J Mol Sci · 2020
0.70
5
The CCL20-CCR6 Axis in Cancer Progression.
PMID: 32707869
Int J Mol Sci · 2020
0.64