CCL3

Chr 17

C-C motif chemokine ligand 3

Also known as: G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI, SCYA3

NCBI Gene: 6348ENSG00000277632UniProt: P10147

The protein functions as a monokine (macrophage inflammatory protein 1 alpha) that binds to CCR1, CCR4 and CCR5 receptors to mediate inflammatory and chemokinetic responses, and serves as a major HIV-suppressive factor produced by CD8+ T-cells. Polymorphisms in this gene are associated with resistance to HIV-1 infection through a dominant negative mechanism. The inheritance pattern for HIV resistance appears to follow a dominant pattern based on the predicted dominant negative pathogenicity mechanism.

Summary from RefSeq, OMIM, UniProt, Mechanism

Primary Disease Associations & Inheritance

{HIV infection, resistance to}MIM #609423
6
Active trials
325
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
1.04
LOEUF
DN
Mechanism· predicted
Clinical Summary— CCL3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 15 VUS of 33 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.350
Z-score 1.53
OE 0.22 (0.08–1.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.12Z-score
OE missense 0.95 (0.76–1.20)
51 obs / 53.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.08–1.04)
0≤0.351.4
Missense OE0.95 (0.76–1.20)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 1 / 4.5Missense obs/exp: 51 / 53.5Syn Z: 0.15
DN
0.74top 25%
GOF
0.5366th %ile
LOF
0.2092th %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

33 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS15
Likely Benign2
10
Pathogenic
15
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
11
4
0
15
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total01314027

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

View in ClinVar →

Protein Context — Lollipop Plot

CCL3 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
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
CCL3+ neutrophil signature predicts response to neoadjuvant toripalimab plus chemotherapy in patients with hypopharyngeal squamous cell carcinoma: A phase II trial.
Chen F et al.·Clin Cancer Res
2026Cohort
Aging-induced decrease in progenitor B cells enhances the osteoclastogenesis of bone marrow macrophages via ROS-activated Fos/CCL3 signaling‌ pathway.
Sun R et al.·Immun Ageing
2026
CCL3 and LPS combination therapy significantly reduces infection and stimulates wound healing in diabetic mice by boosting proinflammatory responses.
Padmakumari RG et al.·J Invest Dermatol
2026
CCL3 is produced by aged neutrophils across cancers and promotes tumor growth.
Bolli E et al.·Cancer Cell
2026
Rosuvastatin in Combination With Bortezomib Promotes Osteogenesis in Myeloma Bone Disease by Inhibiting the Secretion of CCL3.
Qu F et al.·EJHaem
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