CCL5
protein-codingC-C motif chemokine ligand 5, the group of Chemokine ligands
Gene summary
This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, functions as a chemoattractant for blood monocytes, memory T helper cells and eosinophils. It causes the release of histamine from basophils and activates eosinophils. This cytokine is one of the major HIV-suppressive factors produced by CD8+ cells. It functions as one of the natural ligands for the chemokine receptor chemokine (C-C motif) receptor 5 (CCR5), and it suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]
- D17S136E
- SCYA5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.3 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 CCL5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002985.3. 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 | 0 | |||||
| missense | 10 | 1 | 11 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 11 | 1 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002976.2 | 3 | MANE Select | |
| Ensembl | ENSP00000475057.1 | 3 | MANE Select | |
| RefSeq | NP_001265665.1 | 4 | Standard | |
| Ensembl | ENSP00000474141.2 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prion diseases - Homo sapiens (human)
- Influenza A - Homo sapiens (human)
- TNF signaling pathway - Homo sapiens (human)
- Chemokine signaling pathway - Homo sapiens (human)
- Cytosolic DNA-sensing pathway - Homo sapiens (human)
Biological Process
- MAPK cascade
- dendritic cell chemotaxis
- monocyte chemotaxis
- regulation of chronic inflammatory response
- calcium ion transport
Molecular Function
- phosphatidylinositol phospholipase C activity
- protein kinase activity
- protein binding
- chemokine activity
- phospholipase activator activity
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1- infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1- 68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells (PubMed:23979485). {ECO:0000269|PubMed:1380064, ECO:0000269|PubMed:15923218, ECO:0000269|PubMed:16791620, ECO:0000269|PubMed:17001303, ECO:0000269|PubMed:23979485, ECO:0000269|PubMed:8525373, ECO:0000269|PubMed:9516414}.;
Recessive Scores
- pRec
- 0.467
Intolerance Scores
- LoFtool
- 0.625
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.170