CCL5

Chr 17

C-C motif chemokine ligand 5

Also known as: D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228, eoCP

NCBI Gene: 6352ENSG00000271503UniProt: P13501

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]

Primary Disease Associations & Inheritance

{HIV-1 disease, delayed progression of}MIM #609423
{HIV-1 disease, rapid progression of}MIM #609423
6
Active trials
7
Pathogenic / LP
23
ClinVar variants
8
Pubs (1 yr)
0.4
Missense Z
1.82
LOEUF
Clinical Summary— CCL5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 13 VUS of 23 total submissions
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Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — CCL5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.82LOEUF
pLI 0.002
Z-score 0.06
OE 0.97 (0.46–1.82)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.40Z-score
OE missense 0.86 (0.68–1.08)
51 obs / 59.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.97 (0.46–1.82)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.68–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 4 / 4.1Missense obs/exp: 51 / 59.6Syn Z: -0.65
DN
0.7326th %ile
GOF
0.3590th %ile
LOF
0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

23 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
VUS13
Likely Benign2
Benign1
7
Pathogenic
13
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
0
0
0
VUS
0
9
4
0
13
Likely Benign
0
1
1
0
2
Benign
0
0
1
0
1
Total01013023

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CCL5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Idiopathic Intracranial Hypertension

Biomarkers in the Etiology of Idiopathic Intracranial Hypertension

RECRUITING
NCT06059703Phase NAUniversity Hospital, MontpellierStarted 2023-11-27
Blood punctionCentral blood samplingIntracranial pressure measurement
Knee Osteoarthritis

Dietary Supplementation With Blueberry in OA

ACTIVE NOT RECRUITING
NCT05784545Phase NAUniversity of ExeterStarted 2023-05-22
Blueberry powder supplementMaltodextrin supplementation
Coronary Disease

Genetic Polymorphism Associated With Coronary Heart Disease Susceptibility and Variability of Clopidogrel Response

ACTIVE NOT RECRUITING
NCT03373552Hôpital Universitaire Fattouma BourguibaStarted 2015-08-12
Platelet function assay
Cutaneous Squamous Cell Carcinoma (CSCC)

Next-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.

RECRUITING
NCT07064330Instituto de Investigación Biomédica de SalamancaStarted 2025-07-17
Cemiplimab
Porphyria, Acute Intermittent

Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment

RECRUITING
NCT06273644Phase NANordlandssykehuset HFStarted 2024-01-27
Carbohydrates
Phyllodes Breast TumorArtificial IntelligenceMultiomics

AI-Assisted System for Accurate Diagnosis and Prognosis of Breast Phyllodes Tumors

RECRUITING
NCT06286267Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityStarted 2023-03-01
imaging
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Alkaline Phosphatase-Regulated C-C Motif Chemokine Ligand 5 (CCL5) Functions as a Critical Mediator of Hair Follicle Neogenesis.
Kwack MH et al.·Tissue Eng Regen Med
2026
EZH2 inhibition overcomes immune evasion in lung adenocarcinoma by restoring CCL5-mediated T-cell recruitment and MHC class I antigen presentation.
Lin Q et al.·Acta Biochim Biophys Sin (Shanghai)
2026
PP4 modulates macrophage-neutrophil crosstalk to restrict CCL5 -driven NETosis in sepsis.
Yang FM et al.·Redox Biol
2026
Astrocytic CCL5 orchestrates CCR5-positive neuronal necroptosis in subarachnoid hemorrhage.
Chen P et al.·J Neuroinflammation
2026Open Access
Employing epigenetic protein degradation techniques to block CCL5-mediated photodynamic therapy via a programmed delivery platform.
Yang T et al.·Signal Transduct Target Ther
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients