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CCR6

gene
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Also known as CKR-L3GPR-CY4CMKBR6GPR29DRY-6DCR2BN-1CD196

Summary

CCR6 (C-C motif chemokine receptor 6, HGNC:1607) is a protein-coding gene on chromosome 6q27, encoding C-C chemokine receptor type 6 (P51684). Receptor for the C-C type chemokine CCL20.

This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. The gene is preferentially expressed by immature dendritic cells and memory T cells. The ligand of this receptor is macrophage inflammatory protein 3 alpha (MIP-3 alpha). This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dentritic and T cells during inflammatory and immunological responses. Alternatively spliced transcript variants that encode the same protein have been described for this gene.

Source: NCBI Gene 1235 — RefSeq curated summary.

At a glance

  • GWAS associations: 36
  • Clinical variants (ClinVar): 40 total — 1 pathogenic
  • Phenotypes (HPO): 31
  • Druggable target: yes — 3 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_031409

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1607
Approved symbolCCR6
NameC-C motif chemokine receptor 6
Location6q27
Locus typegene with protein product
StatusApproved
AliasesCKR-L3, GPR-CY4, CMKBR6, GPR29, DRY-6, DCR2, BN-1, CD196
Ensembl geneENSG00000112486
Ensembl biotypeprotein_coding
OMIM601835
Entrez1235

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000341935, ENST00000349984, ENST00000400926, ENST00000643861, ENST00000884634, ENST00000884635, ENST00000884636, ENST00000884637

RefSeq mRNA: 3 — MANE Select: NM_031409 NM_001394582, NM_004367, NM_031409

CCDS: CCDS5298

Canonical transcript exons

ENST00000341935 — 3 exons

ExonStartEnd
ENSE00001385774167123096167123223
ENSE00001412265167136240167139141
ENSE00003804296167136038167136143

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 84.94.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2450 / max 399.3507, expressed in 202 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
711801.9349140
711840.8595124
711830.277257
711820.139628
711850.033715

Top tissues by expression

120 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
lymph nodeUBERON:000002984.94gold quality
vermiform appendixUBERON:000115481.47gold quality
spleenUBERON:000210680.11gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047377.82gold quality
granulocyteCL:000009475.81gold quality
bloodUBERON:000017869.54gold quality
duodenumUBERON:000211467.96gold quality
gall bladderUBERON:000211066.99gold quality
small intestine Peyer’s patchUBERON:000345466.38gold quality
rectumUBERON:000105265.61gold quality
small intestineUBERON:000210865.52gold quality
tonsilUBERON:000237263.99gold quality
mucosa of transverse colonUBERON:000499161.15gold quality
left testisUBERON:000453360.06gold quality
testisUBERON:000047359.68gold quality
right testisUBERON:000453459.22gold quality
bone marrowUBERON:000237158.93gold quality
prefrontal cortexUBERON:000045155.46gold quality
bone marrow cellCL:000209255.01gold quality
smooth muscle tissueUBERON:000113554.32gold quality
islet of LangerhansUBERON:000000654.29gold quality
superior frontal gyrusUBERON:000266153.66gold quality
cortical plateUBERON:000534353.27gold quality
Brodmann (1909) area 9UBERON:001354051.94gold quality
leukocyteCL:000073851.79gold quality
frontal cortexUBERON:000187051.53gold quality
dorsolateral prefrontal cortexUBERON:000983451.49gold quality
colonic epitheliumUBERON:000039751.21gold quality
nucleus accumbensUBERON:000188250.80gold quality
cerebral cortexUBERON:000095650.10gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

ExperimentMarker?Max mean expression
E-GEOD-75688yes243.53
E-CURD-46yes17.39
E-ANND-3yes9.13
E-MTAB-6678yes4.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR3C2, PAX1, RORA, RORC, TP53

Literature-anchored findings (GeneRIF, showing 40)

  • Up-regulation on distinct subpopulations of antigen-activated CD4+ T lymphocytes (PMID:11751947)
  • CCR6 preferentially attracts memory B cells and becomes an efficacious B-cell receptor following cellular activation, acquiring an enhanced function due to changes in the responsiveness of downstream signaling pathways. (PMID:11994436)
  • CCR6, appears to have an important role in the selective recruitment of T cells, in the context of periodontal inflammation. (PMID:12067311)
  • CCR1, CCR6, and CXCR6 are preferentially expressed by the low cytokine-producing CD8 and CD4(-)CD8(-) subsets of natural killer T-cells. (PMID:12070001)
  • Mutating the four extracellular cysteines reveals their differing roles in receptor trafficking, ligand binding, and signaling. (PMID:12081481)
  • Clustering of CCR6 and coassociation with critical integrins such as CD18/beta2 integrin serve to strengthen adhesion between T cells and activated dermal microvascular endothelial cells in vitro. (PMID:12193700)
  • characterized the expression of CCR6 on B cells and B-cell non-Hodgkin’s lymphomas (PMID:12514792)
  • Coincident expression of CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis may contribute to their accumulation in nonlymphoid organs such as skin and bone (PMID:12642342)
  • CCR6 on polarized intestinal epithelial cells, alter specialized intestinal epithelial cell functions, including electrogenic ion secretion and possibly epithelial cell adhesion and migration (PMID:15483227)
  • CCR6 has multiple domains involved in ligand binding and receptor signaling (PMID:15591779)
  • We hypothesize that Mip-3alpha and its CCR6 receptor promote pancreatic cancer cell invasion (PMID:15701269)
  • MIP-3alpha/CCL20 has a role in amplification of the immune response during renal allograft rejection by attraction of CCR6+ inflammatory cells, which may include DC, to the site of inflammation (PMID:16095490)
  • CCR6 mediated signals result in increased IEC migration and proliferation suggesting an important role in intestinal homeostasis and intestinal inflammation by mediating chemotaxis of IEC but also in mediating migration of CRC cells. (PMID:16215992)
  • association between expression level of CCR6 in primary CRC and synchronous liver metastases suggests that CCR6 and its ligand may be involved in the metastatic spread to the liver (PMID:16622267)
  • Findings strongly suggest an association between CCL20/CCR6 expression in human colorectal cancer and the promotion of colorectal liver metastasis. (PMID:16641550)
  • CXCR4 expression in colorectal liver metastases suggests it is a predictive factor. CCL20 and receptor CCR6 expression in hepatocellular carcinomas indicates a role of a CCL20/CCR6 ligand-receptor pair in liver carcinogenesis and progression. (PMID:17075975)
  • Our results add new insight to the important role of the CCL20/CCR6, RANKL system in the bone tissue of rheumatoid arthritis. (PMID:17133360)
  • CCR6-expressing CD8+ T cells have the ability to migrate in response to CCL20, may migrate to tissues such as colon, and are involved in mucosal immunity. (PMID:17171755)
  • Interaction between CCL20 and CCR6 may play a role in chemokine-mediated lymphocyte trafficking during gastric inflammation in Helicobacter infection. (PMID:17562763)
  • T cells expressing CCR6, CXCR3, and CXCR6 act coordinately with respective ligands and Th1 inflammatory cytokines in the alveolitic/granuloma phases of the disease. (PMID:17615381)
  • All IL-17-producing CD4+ T cells expressed CCR6, a receptor found on approximately 50% of CD4+ memory peripheral blood leukocytes. (PMID:18097022)
  • Expression levels of CCR6 in prostate cancer are associated with clinical and pathologic features of more advanced and aggressive prostate cancer. (PMID:18465142)
  • CCL6 is overexpressed in myeloma microenvironment related to osteolytic bone lesions. (PMID:18703490)
  • CCR6 regulation of the actin cytoskeleton orchestrates human beta defensin-2- and CCL20-mediated restitution of colonic epithelial cells (PMID:19233848)
  • the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS. (PMID:19305396)
  • KSHV and K13-mediated induction of CCL20 and CCR6 may contribute to the recruitment of dendritic cells and lymphocytes into the KS lesions, and to tumor growth and metastases. (PMID:19324905)
  • This study demonstrates a different expression of CCL20-positive osteoblasts in osteoarthritis versus rheumatoid arthritis disease that seem to be associated with the presence of infiltrating mononuclear cells. (PMID:19492413)
  • Recombinant human granulocyte colony-stimulating factor significantly decreases the expression of CXCR3 and CCR6 on T cells and preferentially induces T helper cells to a T helper 17 phenotype in peripheral blood harvests (PMID:19539215)
  • Data show that number of peripheral Th17 lymphocytes, expression of CCR6 on Th cells, and ex vivo IL-23, anti-CD3 and anti-CD28 induced production of IL-22 by PBMC were significantly elevated in asthmatic patients. (PMID:19811428)
  • Isoleucine/leucine in the N-terminal alpha-helix region of this beta-defensin is essential for CCR6-mediated chemotaxis. (PMID:20022113)
  • CCR6 ligands inhibit HIV by inducing APOBEC3G. (PMID:20023216)
  • CCR6 mediates induction APOBEC3G expression, resulting in inhibition of HIV infection in highly susceptible CCR6+ cells (PMID:20023216)
  • Data show that recombinant mBD4:Ig and hBD2:Ig fusion proteins retained potent antimicrobial activity against Gram-negative and Gram-positive bacteria, and that these fusion proteins showed specific binding to CCR6-expressing cells. (PMID:20068036)
  • CCR6 positive memory T cells producea suppressive IL-10 but not IL-2 upon stimulation with autologous immature dendritic cells. (PMID:20194631)
  • CCR6 is expressed at higher levels in plasmacytoid dendritic cells from melanoma patients compared to healthy controls. CCR6 may have a role in these cells’ migration to tumor sites where CCL20 is produced. (PMID:20220766)
  • We suggest that CCR4 and CCR6 expression on CD4(+) T cells should be considered as markers of disease activity in systemic lupus erythematosus. (PMID:20334681)
  • We studied a unique cohort of 21 primary lung cancers with matched adrenal metastases for the expression of CX3CR1, CXCR4, CCR6, and CCR7 (PMID:20439195)
  • The CCR6DNP genotype was correlated with the expression level of CCR6 and was associated with the presence of interleukin-17 (IL-17) in the sera of subjects with rheumatoid arthritis (PMID:20453841)
  • CCL20 and CCR6 play a role in the development and progression of pancreatic cancer and may constitute potential targets for novel treatment strategies. (PMID:20459729)
  • human beta-defensin (hBD)2 and 3 are chemotactic for a broad spectrum of leukocytes in a CCR6- and CCR2-dependent manner (PMID:20483750)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_rerioccr6bENSDARG00000038968
danio_rerioccr6aENSDARG00000087474
mus_musculusCcr6ENSMUSG00000040899
rattus_norvegicusCcr6ENSRNOG00000012964

Paralogs (23): CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-C chemokine receptor type 6 — P51684 (reviewed: P51684)

Alternative names: Chemokine receptor-like 3, DRY6, G-protein coupled receptor 29, GPR-CY4, LARC receptor

All UniProt accessions (1): P51684

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the C-C type chemokine CCL20. Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels. Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins. Binds to defensin DEFB1 leading to increase in intracellular calcium ions and cAMP levels. Its binding to DEFB1 is essential for the function of DEFB1 in regulating sperm motility and bactericidal activity. Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects. The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/ memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCR6-mediated signals are essential for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma. CCR6 is essential for the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for the normal migration of Th17 cells in Peyers-patches and other related tissue sites of the intestine and plays a role in regulating effector T-cell balance and distribution in inflamed intestine. Plays an important role in the coordination of early thymocyte precursor migration events important for normal subsequent thymocyte precursor development, but is not required for the formation of normal thymic natural regulatory T-cells (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte precursors. Essential for B-cell localization in the subepithelial dome of Peyers-patches and for efficient B-cell isotype switching to IgA in the Peyers-patches. Essential for appropriate anatomical distribution of memory B-cells in the spleen and for the secondary recall response of memory B-cells. Positively regulates sperm motility and chemotaxis via its binding to CCL20.

Subcellular location. Cell membrane. Cell surface.

Tissue specificity. Sperm. Mainly localized in the tail and in the postacrosomal region but is also found in the midpiece and basal region in a small percentage of sperm cells. Reduced levels found in the sperms of asthenozoospermia and leukocytospermia patients (at protein level). Spleen, lymph nodes, appendix, and fetal liver. Expressed in lymphocytes, T-cells and B-cells but not in natural killer cells, monocytes or granulocytes.

Induction. By IL2/interleukin-2.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (3): NP_001381511, NP_004358, NP_113597* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR000355Chemokine_rcptFamily
IPR004067Chemokine_CCR6Family
IPR017452GPCR_Rhodpsn_7TMDomain
IPR050119CCR1-9-likeFamily

Pfam: PF00001

UniProt features (60 total): mutagenesis site 17, helix 10, sequence conflict 9, topological domain 8, transmembrane region 7, strand 5, glycosylation site 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
6WWZELECTRON MICROSCOPY3.34

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P51684-F179.560.45

Antibody-complex structures (SAbDab): 1 — 6WWZ

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 118–197

Glycosylation sites (2): 7, 23

Mutagenesis-validated functional residues (17):

PositionPhenotype
36no loss of calcium flux but loss of chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
36loss of calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
36no loss of calcium flux but loss of chemotaxis in response to ccl20 stimulation, impaired ccl20-binding and no effect on
57no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
118loss of calcium flux and chemotaxis in response to ccl20 stimulation, impaired ccl20-binding and significant reduction i
131no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
138no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
168no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
197loss of calcium flux and chemotaxis in response to ccl20 stimulation, impaired ccl20-binding and significant reduction i
233no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
266no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
288no loss of calcium flux but loss of chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
288no loss of calcium flux but loss of chemotaxis in response to ccl20 stimulation, impaired ccl20-binding and no effect on
309no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
310no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on cell surface expression.
336reduced calcium flux and chemotaxis in response to ccl20 stimulation, and reduced ccl20-binding. no effect on cell surfa
348no effect on calcium flux and chemotaxis in response to ccl20 stimulation. no effect on ccl20-binding and cell surface e

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

IDPathway
R-HSA-1461957Beta defensins
R-HSA-380108Chemokine receptors bind chemokines
R-HSA-418594G alpha (i) signalling events
R-HSA-1461973Defensins
R-HSA-162582Signal Transduction
R-HSA-168249Innate Immune System
R-HSA-168256Immune System
R-HSA-372790Signaling by GPCR
R-HSA-373076Class A/1 (Rhodopsin-like receptors)
R-HSA-375276Peptide ligand-binding receptors
R-HSA-388396GPCR downstream signalling
R-HSA-500792GPCR ligand binding
R-HSA-6803157Antimicrobial peptides

MSigDB gene sets: 413 (showing top): FUNG_IL2_SIGNALING_2, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOCC_CELL_SURFACE, CERVERA_SDHB_TARGETS_1_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS

GO Biological Process (21): dendritic cell chemotaxis (GO:0002407), leukocyte migration involved in inflammatory response (GO:0002523), chemotaxis (GO:0006935), immune response (GO:0006955), humoral immune response (GO:0006959), cellular defense response (GO:0006968), signal transduction (GO:0007165), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), isotype switching to IgA isotypes (GO:0048290), cell chemotaxis (GO:0060326), positive regulation of flagellated sperm motility involved in capacitation (GO:0060474), lymphocyte migration (GO:0072676), T cell migration (GO:0072678), thymocyte migration (GO:0072679), DN2 thymocyte differentiation (GO:1904155), DN3 thymocyte differentiation (GO:1904156), regulation of T cell migration (GO:2000404), positive regulation of dendritic cell chemotaxis (GO:2000510), G protein-coupled receptor signaling pathway (GO:0007186), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (6): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), signaling receptor activity (GO:0038023), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), sperm flagellum (GO:0036126), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm plasma membrane (GO:0097524), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

CategoryPathways
Signaling by GPCR2
Defensins1
Peptide ligand-binding receptors1
GPCR downstream signalling1
Antimicrobial peptides1
Immune System1
Signal Transduction1
GPCR ligand binding1
Class A/1 (Rhodopsin-like receptors)1
Innate Immune System1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
T cell migration2
T cell differentiation in thymus2
chemokine binding2
plasma membrane2
sperm flagellum2
leukocyte chemotaxis1
dendritic cell migration1
inflammatory response1
leukocyte migration1
response to chemical1
taxis1
immune system process1
response to stimulus1
immune response1
defense response1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
regulation of biological quality1
intracellular signaling cassette1
isotype switching1
chemotaxis1
cell migration1
cellular response to chemical stimulus1
reproductive process1
sperm capacitation1
positive regulation of flagellated sperm motility1
mononuclear cell migration1
lymphocyte migration1
regulation of lymphocyte migration1
dendritic cell chemotaxis1
positive regulation of leukocyte chemotaxis1
positive regulation of mononuclear cell migration1
regulation of dendritic cell chemotaxis1
G protein-coupled receptor activity1
signal transduction1
G protein-coupled chemoattractant receptor activity1

Protein interactions and networks

STRING

1738 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CCR6CCL20P78556999
CCR6DEFB4AO15263995
CCR6CCL2P13500990
CCR6DEFB1P60022989
CCR6DEFB103AP81534976
CCR6CXCL16Q9H2A7975
CCR6CCR2P41597973
CCR6CCL19Q99731969
CCR6CXCL9Q07325945
CCR6CCL3P10147927
CCR6CCL4P13236904
CCR6CCL5P13501904
CCR6CCL17Q92583900
CCR6KLRB1Q12918892
CCR6IL17AQ16552889

IntAct

9 interactions, top by confidence:

ABTypeScore
CCR6PODXLpsi-mi:“MI:0914”(association)0.530
CCR6RAMP2psi-mi:“MI:0915”(physical association)0.400
RAMP3CCR6psi-mi:“MI:0915”(physical association)0.400
QSOX1CCR6psi-mi:“MI:0915”(physical association)0.370
CCR6GPR89Apsi-mi:“MI:0914”(association)0.350

BioGRID (85): CCR6 (Synthetic Growth Defect), QSOX1 (Two-hybrid), CCL20 (Reconstituted Complex), LPCAT3 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), LCLAT1 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ND4 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), CERS6 (Affinity Capture-MS), ATP8B2 (Affinity Capture-MS), MCOLN1 (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), PIGN (Affinity Capture-MS), TSPAN15 (Affinity Capture-MS)

ESM2 similar proteins: A1A5S3, A5PLE7, B0UXR0, B5X337, D4A7K7, O00398, O18982, O54689, O97663, P21556, P25105, P25106, P32249, P35351, P35374, P46002, P47749, P47900, P48042, P49650, P49651, P49685, P50052, P51684, P56412, Q1RMI1, Q28929, Q2NNR5, Q3U507, Q3U6B2, Q3UJF0, Q5ZI82, Q61038, Q62035, Q8BZR0, Q8IYL9, Q8K1Z6, Q924T8, Q95N02, Q95N03

Diamond homologs: A6QNL7, F5HF62, O00590, O08556, O08707, O09027, O18793, O54689, O54814, O55193, O62743, O97571, O97665, O97878, O97879, O97880, O97881, O97882, O97883, O97962, O97975, P21109, P25025, P32246, P35344, P35411, P41597, P46094, P49238, P51675, P51676, P51677, P51678, P51679, P51680, P51681, P51682, P51683, P51684, P51685

SIGNOR signaling

5 interactions.

AEffectBMechanism
hsa-miR-150-5p“down-regulates quantity by repression”CCR6“post transcriptional regulation”
hsa-miR-518a-5p“down-regulates quantity by repression”CCR6“post transcriptional regulation”
CCL20“up-regulates activity”CCR6binding
CCR6“up-regulates activity”MMP9
CCR6up-regulatesM2_polarization

Disease & clinical

Clinical variants and AI predictions

ClinVar

40 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance30
Likely benign6
Benign1

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
253576GRCh37/hg19 6q27(chr6:165443824-170892302)x1Pathogenic

SpliceAI

505 predictions. Top by Δscore:

VariantEffectΔscore
6:167136234:TTCCA:Tacceptor_loss1.0000
6:167136236:CCA:Cacceptor_loss1.0000
6:167136237:CA:Cacceptor_loss1.0000
6:167136238:A:AGacceptor_gain1.0000
6:167136238:AG:Aacceptor_gain1.0000
6:167136239:G:GAacceptor_gain1.0000
6:167136239:GG:Gacceptor_gain1.0000
6:167136239:GGA:Gacceptor_gain1.0000
6:167112011:ATTGG:Adonor_loss0.9900
6:167112012:TTGG:Tdonor_loss0.9900
6:167112015:G:GAdonor_loss0.9900
6:167112015:G:GGdonor_gain0.9900
6:167112016:TAAGT:Tdonor_loss0.9900
6:167136037:GA:Gacceptor_gain0.9900
6:167136139:GCGGG:Gdonor_gain0.9900
6:167136239:GGAAT:Gacceptor_gain0.9900
6:167136036:A:AGacceptor_gain0.9800
6:167136037:G:GGacceptor_gain0.9800
6:167136037:GAGTC:Gacceptor_gain0.9800
6:167136141:GGG:Gdonor_gain0.9800
6:167136142:GG:Gdonor_gain0.9800
6:167136142:GGG:Gdonor_gain0.9800
6:167136143:GG:Gdonor_gain0.9800
6:167136143:GGTAA:Gdonor_loss0.9800
6:167136144:G:Cdonor_loss0.9800
6:167136145:T:Adonor_loss0.9800
6:167112012:TTG:Tdonor_gain0.9700
6:167135272:G:GTdonor_gain0.9700
6:167136032:TCTTA:Tacceptor_loss0.9700
6:167136035:TAGA:Tacceptor_loss0.9700

AlphaMissense

2466 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
6:167136648:A:CS140R0.998
6:167136650:C:AS140R0.998
6:167136650:C:GS140R0.998
6:167137197:T:CF323L0.997
6:167137199:C:AF323L0.997
6:167137199:C:GF323L0.997
6:167136422:T:AN64K0.996
6:167136422:T:GN64K0.996
6:167136658:G:CR143P0.996
6:167136744:T:AW172R0.996
6:167136744:T:CW172R0.996
6:167137017:T:CF263L0.995
6:167137019:T:AF263L0.995
6:167137019:T:GF263L0.995
6:167136563:G:CW111C0.994
6:167136563:G:TW111C0.994
6:167136417:G:AG63R0.993
6:167136417:G:CG63R0.993
6:167136408:G:CG60R0.992
6:167136504:G:CD92H0.992
6:167136505:A:CD92A0.992
6:167137168:C:AP313H0.992
6:167136506:C:AD92E0.991
6:167136506:C:GD92E0.991
6:167136582:T:AC118S0.991
6:167136583:G:CC118S0.991
6:167136819:T:AC197S0.991
6:167136820:G:CC197S0.991
6:167136399:T:CC57R0.990
6:167136409:G:AG60D0.990

dbSNP variants (sampled 300 via entrez): RS1000008485 (6:167122974 C>A,T), RS1000020625 (6:167114817 C>T), RS1000091334 (6:167115208 T>C,G), RS1000111774 (6:167129585 T>C), RS1000651818 (6:167137986 C>T), RS1000655492 (6:167125465 A>G), RS1000836364 (6:167129284 C>T), RS1000946942 (6:167134845 C>A), RS1001057082 (6:167113748 T>C), RS1001149163 (6:167115256 C>G), RS1001183702 (6:167122599 G>A,C), RS1001235536 (6:167129204 C>A), RS1001445656 (6:167134628 G>A), RS1001586794 (6:167112395 C>T), RS1001861591 (6:167113737 G>A)

Disease associations

OMIM: gene MIM:601835 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPOTerm
HP:0000083Renal insufficiency
HP:0000217Xerostomia
HP:0000670Carious teeth
HP:0000951Abnormality of the skin
HP:0001000Abnormality of skin pigmentation
HP:0001053Hypopigmented skin patches
HP:0001324Muscle weakness
HP:0001369Arthritis
HP:0001371Flexion contracture
HP:0001635Congestive heart failure
HP:0002015Dysphagia
HP:0002017Nausea and vomiting
HP:0002020Gastroesophageal reflux
HP:0002024Malabsorption
HP:0002092Pulmonary arterial hypertension
HP:0002094Dyspnea
HP:0002113Pulmonary infiltrates
HP:0002206Pulmonary fibrosis
HP:0002797Osteolysis
HP:0002829Arthralgia
HP:0002960Autoimmunity
HP:0008366Foot joint contracture
HP:0009473Joint contracture of the hand
HP:0030016Dyspareunia
HP:0030142Abnormal bowel sounds
HP:0100520Oliguria
HP:0100579Mucosal telangiectasiae
HP:0100585Telangiectasia of the skin
HP:0100735Hypertensive crisis
HP:0100958Narrow foramen obturatorium

GWAS associations

36 associations (top):

StudyTraitp-value
GCST000207_9Crohn’s disease1.000000e-12
GCST000677_1Rheumatoid arthritis8.000000e-19
GCST000692_2Vitiligo1.000000e-16
GCST000705_7Crohn’s disease6.000000e-08
GCST000879_22Crohn’s disease3.000000e-12
GCST001725_92Inflammatory bowel disease7.000000e-21
GCST002094_6Crohn’s disease8.000000e-12
GCST002228_3Social autistic-like traits3.000000e-06
GCST002318_145Rheumatoid arthritis5.000000e-35
GCST002318_146Rheumatoid arthritis1.000000e-22
GCST002318_62Rheumatoid arthritis2.000000e-18
GCST002433_4Rheumatoid arthritis7.000000e-15
GCST002433_7Rheumatoid arthritis2.000000e-10
GCST002434_3Rheumatoid arthritis4.000000e-09
GCST002468_5Triglycerides7.000000e-09
GCST002951_9Response to zileuton treatment in asthma (FEV1 change interaction)4.000000e-07
GCST003602_2Inflammatory bowel disease1.000000e-06
GCST004131_51Inflammatory bowel disease9.000000e-15
GCST004132_22Crohn’s disease2.000000e-20
GCST004302_13Primary biliary cholangitis6.000000e-07
GCST004748_52Lung cancer9.000000e-06
GCST004785_22Vitiligo2.000000e-18
GCST005524_5Autoimmune thyroid diseases (Graves disease or Hashimoto’s thyroiditis)2.000000e-07
GCST005526_5Graves’ disease3.000000e-07
GCST005568_21Rheumatoid arthritis (ACPA-positive)3.000000e-10
GCST005568_36Rheumatoid arthritis (ACPA-positive)1.000000e-12
GCST005569_10Rheumatoid arthritis2.000000e-08
GCST005569_43Rheumatoid arthritis3.000000e-06
GCST005987_42Albumin-globulin ratio1.000000e-08
GCST006048_4Rheumatoid arthritis (ACPA-positive)5.000000e-17

EFO canonical traits (5, from GWAS)

EFO IDTrait name
EFO:0005426autism spectrum disorder symptom
EFO:0004530triglyceride measurement
EFO:0005921FEV change measurement
EFO:0005128albumin:globulin ratio measurement
EFO:0010176keratinocyte carcinoma

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4423 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,764 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1516474TEGASEROD MALEATE41,823
CHEMBL216981NAVARIXIN ANHYDROUS2932
CHEMBL6068520PF-0705489419

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (4 total), top 4:

LigandActionAffinityParameter
[125I]CCL20 (human)Full agonist10.0pKd
CCL20-SEAP(His)6Full agonist9.0pKd
CCL20Full agonist8.5pIC50
PF-07054894Antagonist8.24pIC50

Binding affinities (BindingDB)

71 measured of 82 human assays (292 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
2-hydroxy-N,N-dimethyl-3-[[2-[[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzamideIC501.4 nMUS-9090596: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated pathologies
methyl (2R)-1-[2-hydroxy-3-[[2-[[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzoyl]pyrrolidine-2-carboxylateIC505.8 nMUS-9090596: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated pathologies
2,5-bis(chloranyl)-3-[2-(dimethylamino)-1,3-thiazol-5-yl]-6-pyrrolidin-1-yl-cyclohexa-2,5-diene-1,4-dioneEC50210 nM
MLS000374486IC50348 nM
(NE)-N-[3-[(4-hydroxyphenyl)amino]-4-oxidanylidene-naphthalen-1-ylidene]-4-methoxy-benzenesulfonamideIC50441 nM
3-[4-chloro-2-hydroxy-3-(4-methylpiperazin-1-yl)sulfonylanilino]-4-[[(R)-(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino]cyclobutane-1,2-dioneIC50450 nMUS-9090596: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated pathologies
MLS000585839IC50453 nM
(NZ)-N-[3-(4-hydroxyanilino)-4-keto-1-naphthylidene]thiophene-2-sulfonamideIC50656 nM
3-[[(4E)-4-(2,4-dimethylphenyl)sulfonylimino-1-keto-2-naphthyl]amino]benzoic acidIC50919 nM
(E)-2-cyano-3-[5-(4-nitrophenyl)-2-furanyl]-N-(4-thiophen-2-yl-2-thiazolyl)-2-propenamideIC501180 nM
4-[(E)-[3-(2-carbomethoxyanilino)-4-keto-1-naphthylidene]amino]sulfonylbenzoic acidIC501260 nM
(NE)-4-ethyl-N-[3-(4-hydroxyanilino)-4-keto-1-naphthylidene]benzenesulfonamideIC501280 nM
3-ethoxy-N-(m-tolylthiocarbamoyl)benzamideEC501330 nM
MLS000335562EC501380 nM
1-(1H-benzimidazol-2-yl)-3-methyl-4-phenyl-1H-pyrazol-5-amineEC501420 nM
6-chloro-2-hydroxy-N,N-dimethyl-3-[[2-[[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzenesulfonamideIC501500 nMUS-9090596: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated pathologies
4-[[(4E)-1-keto-4-mesitylsulfonylimino-2-naphthyl]amino]benzoic acidIC501680 nM
5-[(2E)-2-(8-oxidanylidenequinolin-5-ylidene)hydrazinyl]naphthalene-1-sulfonic acidIC501700 nM
1-ethoxy-4-(2-nitrovinyl)naphthaleneIC502180 nM
7-(hydroxymethyl)-2-(2-phenylphenyl)-4,7a-dihydro-3aH-octahydro-1H-4,7-epoxyisoindole-1,3-dioneEC502260 nM
2,5-bis(chloranyl)-3-piperidin-1-yl-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dioneEC502320 nM
2-azanylidene-3-[5-[(3-chlorophenyl)methyl]-1,3-thiazol-2-yl]-1,3-thiazolidin-4-oneEC502530 nM
2-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-4-(3-ethoxy-4-hydroxybenzylidene)-5-phenyl-2,4-dihydro-3H-pyrazol-3-oneIC502540 nM
cid_4561725EC502680 nM
MLS000777166IC503770 nM
4-((3E)-3-{[5-(4-nitrophenyl)-2-furyl]methylene}-2-oxo-5-phenyl-2,3-dihydro-1H-pyrrol-1-yl)benzoic acidIC503930 nM
(6Z)-6-[1-[N’-(2-quinolyl)hydrazino]ethylidene]cyclohexa-2,4-dien-1-oneIC504120 nM
MLS000757112IC504290 nM
9-(3,6-diketocyclohexa-1,4-dien-1-yl)-2-phenethyl-3,6,7,8-tetrahydropyrido[1,2-a]pyrazine-1,4-quinoneIC504750 nM
2-[(5Z)-5-[1-[2-(3-bromoanilino)-2-keto-ethyl]-2-keto-indolin-3-ylidene]-4-keto-2-thioxo-thiazolidin-3-yl]ethanesulfonic acidIC504920 nM
(5Z)-5-[(2-phenyl-1H-indol-3-yl)methylene]-2-thioxo-thiazolidin-4-oneIC504970 nM
2-chloro-N-(3,4-dimethylphenyl)-5-(2,5-dioxo-1-pyrrolyl)benzamideIC505400 nM
(1Z)-1-(1,3-benzodioxol-5-yl)ethan-1-one N-phenylthiosemicarbazoneEC505460 nM
2-chloranyl-3-(1H-indazol-6-ylamino)naphthalene-1,4-dioneIC506250 nM
MLS002153995IC506410 nM
2-acetamido-4,5-dinitro-benzoic acid ethyl esterEC507180 nM
SMR000439471IC507220 nM
2-(2,5-dinitro-3-thienyl)pyrimidineEC507570 nM
5-(4-chlorophenyl)-N-[(5-methyl-2-oxidanyl-phenyl)carbamothioyl]furan-2-carboxamideIC507680 nM
(1-methylbenzimidazol-2-yl)-(1-propylbenzimidazol-2-yl)amineIC507900 nM
6-Nitro-quinolin-8-olEC507940 nM
MLS002695979IC509070 nM
(E)-2-cyano-3-[5-(3-nitrophenyl)-2-furanyl]-N-(4-thiophen-2-yl-2-thiazolyl)-2-propenamideEC509150 nM
2-Butenoic acid, 3-[(1,3-dihydroxy-2-naphthalenyl)thio]-, ethyl ester, (Z)-IC5010500 nM
cid_4261263IC5011000 nM
cid_2884240IC5012100 nM
(3Z)-3-(1-methyl-5-oxidanylidene-2-sulfanylidene-imidazolidin-4-ylidene)-1H-indol-2-oneEC5013400 nM
1,4-diketo-3-p-anisyl-naphthalene-2-carboxylic acid ethyl esterEC5013600 nM
cid_805087IC5013900 nM
SMR000254838IC5014800 nM

ChEMBL bioactivities

283 potent at pChembl≥5 of 507 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.21IC500.62nMCHEMBL5517631
9.00IC501nMCHEMBL6177449
8.92IC501.2nMCHEMBL6176579
8.85IC501.4nMCHEMBL3704570
8.80IC501.6nMCHEMBL6049426
8.74IC501.8nMCHEMBL6173557
8.72IC501.9nMCHEMBL3704573
8.70IC502nMCHEMBL5979255
8.66IC502.2nMCHEMBL5979255
8.66IC502.2nMCHEMBL3952996
8.60IC502.5nMCHEMBL6173137
8.60IC502.5nMCHEMBL6170643
8.54IC502.9nMCHEMBL5561521
8.51Ki3.09nMPF-07054894
8.51Ki3.1nMPF-07054894
8.47IC503.4nMCHEMBL3701196
8.31IC504.9nMCHEMBL6172570
8.25IC505.6nMCHEMBL6177228
8.24IC505.8nMCHEMBL3701188
8.24IC505.7nMPF-07054894
8.22IC506nMCHEMBL4248604
8.22IC506nMCHEMBL5557717
8.22IC506nMCHEMBL3951994
8.22IC506nMCHEMBL5758919
8.22IC506nMCHEMBL5830817
8.22IC506nMCHEMBL6172267
8.21IC506.1nMCHEMBL5532548
8.21IC506.1nMCHEMBL6176579
8.10IC508nMCHEMBL3951994
8.10IC508nMCHEMBL6056260
8.09IC508.1nMCHEMBL5564432
8.06IC508.8nMCHEMBL5559793
8.06IC508.7nMCHEMBL5558277
8.06IC508.8nMCHEMBL3901913
8.06Ki8.7nMCHEMBL6172267
8.05IC509nMCHEMBL5977734
8.04IC509.2nMCHEMBL5563619
8.01IC509.8nMCHEMBL5559785
8.01IC509.7nMCHEMBL3901913
8.00IC5010nMCHEMBL5563681
7.96IC5011nMCHEMBL3904195
7.92IC5012nMCHEMBL4239904
7.92IC5012nMCHEMBL5561521
7.92IC5012nMCHEMBL5936951
7.92Ki12nMCHEMBL6172570
7.89IC5013nMCHEMBL4250007
7.89IC5013nMCHEMBL5559983
7.89IC5013nMCHEMBL5563681
7.85IC5014nMCHEMBL5940263
7.77IC5017nMCHEMBL4245355

PubChem BioAssay actives

114 with measured affinity, of 165 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-[3-[3-[(S)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]phenyl]-1,2,4-oxadiazol-5-yl]-1,1,1-trifluoropropan-2-ol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0006uM
(1,3-dimethylazetidin-3-yl)-(5-pyrrolidin-1-yl-3-pyridinyl)-[4-(trifluoromethoxy)phenyl]methanol2071636: Antagonist activity at CCR6 in human CCR6+ CD4+ Th17 cells assessed as inhibition of cell migration to CCL20 measured after 24 hrs in presence of CCL20ic500.0029uM
4-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]pyridine-2-carboxamide1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0060uM
(S)-(1,3-dimethylazetidin-3-yl)-[3-[5-(1-methoxy-2-methylpropan-2-yl)-1,2,4-oxadiazol-3-yl]phenyl]-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0060uM
(S)-(1,3-dimethylazetidin-3-yl)-[3-[3-(oxan-4-yloxymethyl)-1,2,4-oxadiazol-5-yl]phenyl]-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0061uM
5-[5-[(R)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]pyridazin-3-yl]-5-azaspiro[2.4]heptan-6-one2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0081uM
(S)-(1,3-dimethylazetidin-3-yl)-[3-[3-(oxan-4-yl)-1,2,4-oxadiazol-5-yl]phenyl]-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0087uM
(R)-(1,3-dimethylazetidin-3-yl)-(4-propan-2-ylphenyl)-(6-pyrrolidin-1-ylpyridazin-4-yl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0088uM
1-[3-[3-[(S)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]phenyl]-1,2,4-oxadiazol-5-yl]cyclobutan-1-ol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0092uM
(R)-[5-[(3S,4R)-3,4-difluoropyrrolidin-1-yl]-3-pyridinyl]-(1,3-dimethylazetidin-3-yl)-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0098uM
2-[3-[3-[(S)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]phenyl]-1,2,4-oxadiazol-5-yl]propan-2-ol2071676: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in T cells incubated for 30 mins by flow cytometryic500.0100uM
3-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]benzamide1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0120uM
4-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]benzamide1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0130uM
1-[3-[3-[(S)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]phenyl]-1,2,4-oxadiazol-5-yl]-2-methylpropan-2-ol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0130uM
4-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]benzonitrile1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0170uM
5-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]pyridine-2-carboxamide1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0170uM
(S)-(1,3-dimethylazetidin-3-yl)-[3-[5-(oxan-4-yl)-1,2,4-oxadiazol-3-yl]phenyl]-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0190uM
(S)-(1,3-dimethylazetidin-3-yl)-[3-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]phenyl]-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0190uM
N-[4-(4-pyridin-4-ylphenyl)sulfonylcyclohexyl]-5-(trifluoromethyl)pyridin-2-amine1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0240uM
(R)-(1,3-dimethylazetidin-3-yl)-(4-propan-2-ylphenyl)-(5-pyrrolidin-1-yl-3-pyridinyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0240uM
5-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]pyridine-2-carbonitrile1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0270uM
(1,3-dimethylazetidin-3-yl)-(6-pyrrolidin-1-ylpyridazin-4-yl)-[4-(trifluoromethoxy)phenyl]methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0270uM
1-[5-[(R)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]-3-pyridinyl]-4-propan-2-ylpyrrolidin-2-one2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0280uM
2-[(3S)-1-[5-[(R)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]-3-pyridinyl]pyrrolidin-3-yl]propan-2-ol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0290uM
3-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]benzonitrile1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0310uM
(1,3-dimethylazetidin-3-yl)-[3-(2-methylpropoxy)phenyl]-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.0374uM
(S)-(3-chlorophenyl)-(1,3-dimethylazetidin-3-yl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.0380uM
(R)-(1,3-dimethylazetidin-3-yl)-[5-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-3-pyridinyl]-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0470uM
2-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]benzonitrile1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0480uM
N-[4-(4-pyridin-3-ylphenyl)sulfonylcyclohexyl]-5-(trifluoromethyl)pyridin-2-amine1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0480uM
(1,3-dimethylazetidin-3-yl)-(2-pyrrolidin-1-yl-4-pyridinyl)-[4-(trifluoromethoxy)phenyl]methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.0530uM
(1,3-dimethylazetidin-3-yl)-(5-ethoxy-3-pyridinyl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.0700uM
(3-chlorophenyl)-(1,3-dimethylazetidin-3-yl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.0700uM
N-[4-(4-phenylphenyl)sulfonylcyclohexyl]-5-(trifluoromethyl)pyridin-2-amine1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.0760uM
(1,3-dimethylazetidin-3-yl)-(3-methoxyphenyl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.0912uM
1-[5-[(R)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]-3-pyridinyl]pyrrolidin-2-one2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.1110uM
(3S)-1-[5-[(R)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]-3-pyridinyl]pyrrolidin-3-ol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.1190uM
(R)-(1,3-dimethylazetidin-3-yl)-(5-morpholin-4-yl-3-pyridinyl)-(4-propan-2-ylphenyl)methanol2071628: Antagonist activity at CCR6 in human whole blood assessed as inhibition of CCL20-stimulated receptor internalization in lymphocytes incubated for 30 mins by flow cytometryic500.1300uM
1-[5-[(R)-(1,3-dimethylazetidin-3-yl)-hydroxy-(4-propan-2-ylphenyl)methyl]-3-pyridinyl]-4-(1,3-dimethylpyrazol-4-yl)pyrrolidin-2-one2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.1370uM
6-[[4-[4-(4-tert-butylphenyl)phenyl]sulfonylcyclohexyl]amino]pyridine-3-carbonitrile1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.1400uM
(4-chlorophenyl)-(1,3-dimethylazetidin-3-yl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.1530uM
(1,3-dimethylazetidin-3-yl)-(3-pyrrolidin-1-ylphenyl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.1550uM
N-[1-(4-phenylphenyl)sulfonylpiperidin-4-yl]-5-(trifluoromethyl)pyridin-2-amine1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.1700uM
(1,3-dimethylazetidin-3-yl)-phenyl-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.1780uM
(1,3-dimethylazetidin-3-yl)-(2-fluorophenyl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.1800uM
6-[[4-(4-phenylphenyl)sulfonylcyclohexyl]amino]pyridine-3-carbonitrile1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.1900uM
(1,3-dimethylazetidin-3-yl)-(5-methoxy-3-pyridinyl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.2090uM
6-[[1-(4-tert-butylphenyl)sulfonylpiperidin-4-yl]amino]pyridine-3-carbonitrile1399325: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in CCL20-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assayic500.2200uM
(3-chlorophenyl)-(3-fluoro-1-methylazetidin-3-yl)-[4-(trifluoromethoxy)phenyl]methanol2071627: Antagonist activity at human CCR6 expressed in HEK293 cells assessed as inhibition of CCL20-stimulated intracellular calcium mobilization by Fluo-8-AM based FLIPR analysisic500.2300uM
6-[[1-(4-phenylphenyl)sulfonylpiperidin-4-yl]amino]pyridine-3-carbonitrile1399330: Inhibition of human CCR6 expressed in CHO cells assessed as decrease in human CCL20-dependent cell migration incubated for 4 hrs by Diff-Quik staining based assayic500.2400uM

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
(+)-JQ1 compounddecreases expression, increases expression3
Benzo(a)pyreneaffects methylation, decreases expression, increases expression3
Nickeldecreases expression, increases expression, affects expression, decreases reaction2
Tetrachlorodibenzodioxinincreases expression2
Asian ginsengdecreases reaction, increases expression, affects cotreatment1
bisphenol Adecreases methylation1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)affects expression, affects response to substance1
trichostatin Aaffects expression, decreases reaction1
thallium sulfatedecreases expression1
zinc chloridedecreases expression1
sodium arseniteaffects methylation1
ferrous sulfatedecreases expression1
1-nitropyrenedecreases expression1
di-n-butylphosphoric acidaffects expression1
chloropicrinincreases expression1
6-formylindolo(3,2-b)carbazoleaffects expression1
lipopolysaccharide, E. coli O26-B6decreases expression1
2-(1’H-indole-3’-carbonyl)thiazole-4-carboxylic acid methyl esteraffects expression1
theaflavin-3,3’-digallateaffects expression1
Irinotecandecreases expression1
Arsenic Trioxidedecreases expression1
Leflunomideincreases expression1
Acetaminophendecreases expression1
Arsenicaffects expression1
Vehicle Emissionsdecreases methylation1
Cannabidioldecreases expression, decreases reaction1
Cannabinoidsdecreases expression, decreases reaction, increases abundance1
Diethylhexyl Phthalatedecreases reaction, increases expression, affects cotreatment1
Diurondecreases expression1
Nicotinedecreases expression1

ChEMBL screening assays

60 unique, capped per target: 33 functional, 27 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1010852BindingInhibition of CCR6 receptorDiscovery of a potent, selective and orally bioavailable 3,9-diazaspiro[5.5]undeca-2-one CCR5 antagonist. — Bioorg Med Chem Lett
CHEMBL1738164FunctionalPUBCHEM_BIOASSAY: Dose Response confirmation of small molecule antagonists of the CCR6 receptor: a luminescent beta-arrestin assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID493098, AID493121, AID493159]PubChem BioAssay data set

Cellosaurus cell lines

11 cell lines: 6 cancer cell line, 3 spontaneously immortalized cell line, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_A6URNP-2/CD4/CCR6Cancer cell lineMale
CVCL_B8CQAbcam HCT 116 CCR6 KOCancer cell lineMale
CVCL_B8THAbcam MCF-7 CCR6 KOCancer cell lineFemale
CVCL_B9EYAbcam A-549 CCR6 KOCancer cell lineMale
CVCL_D2T1CHO/hCCR6Spontaneously immortalized cell lineFemale
CVCL_E6IWHEK 293/CCR6Transformed cell lineFemale
CVCL_KU90cAMP Hunter CHO-K1 CCR6 GiSpontaneously immortalized cell lineFemale
CVCL_KW60PathHunter CHO-K1 CCR6 beta-arrestinSpontaneously immortalized cell lineFemale
CVCL_KZ97PathHunter U2OS CCR6 Activated GPCR InternalizationCancer cell lineFemale
CVCL_UE36293T human CCR6Transformed cell lineFemale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot