CCR6
protein-codingC-C motif chemokine receptor 6, the group of C-C motif chemokine receptors|CD molecules
Gene summary
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. [provided by RefSeq, Jul 2008]
- STRL22
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~27.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCR6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031409.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 3 | |||
| missense | 27 | 6 | 33 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 27 | 8 | 1 | 36 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_113597.2 | 2 | MANE Select | |
| Ensembl | ENSP00000343952.5 | 2 | MANE Select | |
| RefSeq | NP_001381511.1 | 2 | Standard | |
| RefSeq | NP_004358.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chemokine signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- Peptide GPCRs
- Chemokine signaling pathway
- GPCRs, Class A Rhodopsin-like
Biological Process
- dendritic cell chemotaxis
- leukocyte migration involved in inflammatory response
- chemotaxis
- immune response
- humoral immune response
Molecular Function
- chemokine receptor activity
- protein binding
- C-C chemokine receptor activity
- chemokine binding
- C-C chemokine binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- external side of plasma membrane
- cell surface
- sperm flagellum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000341935
- Coding exons
- 2
- Length
- 27890
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125748
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.13 | 127 | 215 | 0.591 | 0.0000120 | 2459 |
| Missense (PolyPhen) | 21 | 52.824 | 0.39755 | 664 | ||
| Synonymous | -0.582 | 100 | 92.9 | 1.08 | 0.00000602 | 749 |
| Loss of Function | 1.48 | 5 | 10.1 | 0.496 | 5.98e-7 | 117 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins (PubMed:25585877). 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 (PubMed:25122636). Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects (PubMed:20068036). 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 (PubMed:21376174). CCR6 is essential for the recruitment of both the proinflammatory 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 (By similarity). Positively regulates sperm motility and chemotaxis via its binding to CCL20 (PubMed:23765988). {ECO:0000250|UniProtKB:O54689, ECO:0000269|PubMed:20068036, ECO:0000269|PubMed:23765988, ECO:0000269|PubMed:25122636, ECO:0000269|PubMed:9169459, ECO:0000303|PubMed:21376174, ECO:0000303|PubMed:25585877}.;
Recessive Scores
- pRec
- 0.0938
Intolerance Scores
- LoFtool
- 0.479
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.35
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.834
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |