CCL2

Chr 17

C-C motif chemokine ligand 2

Also known as: GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1, SCYA2, SMC-CF

NCBI Gene: 6347ENSG00000108691UniProt: P13500

This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]

Primary Disease Associations & Inheritance

{HIV-1, resistance to}MIM #609423
12
Active trials
25
ClinVar variants
4
Pathogenic / LP
1.2
Missense Z
1.00
LOEUF
8
Pubs (2 yr)
Clinical Summary— CCL2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 17 VUS of 25 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
1.00LOEUF
pLI 0.608
Z-score 1.59
OE 0.00 (0.00–1.00)
Moderately constrained

Typical tolerance to LoF variation

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.
1.19Z-score
OE missense 0.54 (0.40–0.74)
29 obs / 53.5 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.0.00 (0.00–1.00)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.40–0.74)
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.1.06
0≤1.21.6
LoF obs/exp: 0 / 3.0Missense obs/exp: 29 / 53.5Syn Z: -0.21

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS17
Likely Benign3
Benign1
4
Pathogenic
17
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
6
11
0
17
Likely Benign
0
0
2
1
3
Benign
0
0
0
1
1
Total0617225

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

View in ClinVar →

Protein Context — Lollipop Plot

CCL2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{HIV-1, resistance to}

MIM #609423

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting hepatic macrophages to treat liver diseases.
Tacke F·J Hepatol
2017Review
FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2.
Xie M et al.·J Hepatol
2023
Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure.
Hanna A et al.·Cardiovasc Drugs Ther
2020Review
Spatial dissection of tumour microenvironments in gastric cancers reveals the immunosuppressive crosstalk between CCL2+ fibroblasts and STAT3-activated macrophages.
Lee SH et al.·Gut
2025
Losartan Blocks Osteosarcoma-Elicited Monocyte Recruitment, and Combined With the Kinase Inhibitor Toceranib, Exerts Significant Clinical Benefit in Canine Metastatic Osteosarcoma.
Regan DP et al.·Clin Cancer Res
2022
Role of the CCL2-CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting.
Xu M et al.·Cell Prolif
2021Review
Role of the CCL2-CCR2 axis in cardiovascular disease: Pathogenesis and clinical implications.
Zhang H et al.·Front Immunol
2022Review
LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression.
Zhao L et al.·Cell Mol Biol Lett
2024
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis.
Qian BZ et al.·Nature
2011
The role of CCL2/CCR2 axis in cancer and inflammation: The next frontier in nanomedicine.
Pozzi S et al.·Adv Drug Deliv Rev
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PRMT6 is required for initiating and amplifying macrophage-induced inflammation in heterotopic ossification by increasing CCL2 expression.
Chu W et al.·Bone Res
2026
tPLGA nanoparticles combined with CCL2/CCR2 inhibitor mitigate post-thrombolytic hemorrhagic transformation.
Luo F et al.·Biomater Sci
2026
CCL2 drives macrophage M2 polarization via CH25H-mediated metabolic reprogramming to ameliorate post-myocardial infarction remodeling.
Yang C et al.·Cell Signal
2026Functional
The STAT3-ZEB1 axis contributes to CCL2-mediated resistance to osimertinib in lung cancer.
Chang TH et al.·Front Oncol
2026Open Access
Jurkat T-Cell Antigen-Independent Elimination of PMA-Activated Neuroblastoma Cells Is Triggered by CCL2/CCR2, Depends Upon Lipid Raft LFA1/ICAM1 Immune Synapses, Is Mediated by m-TRAIL and Is Augmented by the TrkAIII Oncoprotein.
Sbaffone M et al.·Int J Mol Sci
2026
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Does C-C Motif Chemokine Ligand 2 (CCL2) Link Obesity to a Pro-Inflammatory State?
Dommel S et al.·Int J Mol Sci
2021
Rational Design of de novo CCL2 Binding Peptides
Davidoff Aguas E et al.·Adv Theory Simul
2023
CC Chemokine Ligand-2: A Promising Target for Overcoming Anticancer Drug Resistance
Shi Z et al.·Cancers (Basel)
2022
The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis
Yoshimura T et al.·Cell Mol Immunol
2023
Role of CC-chemokine ligand 2 in gynecological cancer
Zhang JJ et al.·Cancer Cell Int
2022
CC Chemokine 2 Promotes Ovarian Cancer Progression through the MEK/ERK/MAP3K19 Signaling Pathway
Liu W et al.·Int J Mol Sci
2023
Expression of a Fungal Lectin in Arabidopsis Enhances Plant Growth and Resistance Toward Microbial Pathogens and a Plant-Parasitic Nematode
Moradi A et al.·Front Plant Sci
2021
The effect of C-C motif chemokine ligand 2 supplementation on in vitro maturation of porcine cumulus-oocyte complexes and subsequent developmental competence after parthenogenetic activation
Kim S et al.·Front Vet Sci
2023
C-C Motif Chemokine Ligand 2 Enhances Macrophage Chemotaxis, Osteogenesis, and Angiogenesis during the Inflammatory Phase of Bone Regeneration
Shinohara I et al.·Biomolecules
2023
Anti-CCL2 antibody combined with etoposide prolongs survival in a minimal residual disease mouse model of neuroblastoma
Lascano D et al.·Sci Rep
2023Functional
Top 10 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
RETT Syndrome With Proven MECP2 MutationRett Syndrome

Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome

NOT YET RECRUITING
NCT07257978Phase PHASE2, PHASE3Fenix Innovation GroupStarted 2026-07-01
NTI164Placebo
Low Back Pain

The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain "BETA"

ACTIVE NOT RECRUITING
NCT05544656Phase PHASE3Semmelweis UniversityStarted 2019-12-13
Tolperisone HydrochloridePlacebo
DysferlinopathyMiyoshi MyopathyLGMDR2

Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy (LGMD R2) in the RF

ENROLLING BY INVITATION
NCT04824040Artgen BiotechStarted 2020-01-15
COPD

Immuno-inflammatory Response of Erdosteine in COPD

NOT YET RECRUITING
NCT07329946Phase NAPierachille Santus, MD, PhDStarted 2026-02-28
ErdosteineStandard of Care (SOC)
Atherosclerosis Cardiovascular DiseaseObesityMetabolic Syndrome

Deciphering the Effect of Moderate Wine Consumption on Healthy Aging Through Postprandial Extracellular Vesicles.

RECRUITING
NCT07361887Phase NAUniversity of SevilleStarted 2025-11-01
White WineRed WineWater
Iron DeficiencyIron Deficiency Anaemia

Assessing the Effect of a Mineral-enriched Powder on Iron Deficiency in Women of Reproductive Age

ACTIVE NOT RECRUITING
NCT05990166Phase PHASE2Carleton UniversityStarted 2023-04-27
Mineral-enriched powderPlacebo powder
Amyotrophic Lateral Sclerosis (ALS)

A Patient-tailored Genetic/Biomarker/iPSC Combined Approach in ALS - PERMEALS

RECRUITING
NCT06917924A.O.U. Città della Salute e della ScienzaStarted 2023-05-20
lumbar puncture
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
AutismAutism Spectrum DisorderAutism Disorder

NTI164 in Autism Spectrum Disorder

NOT YET RECRUITING
NCT07257939Phase PHASE3Fenix Innovation GroupStarted 2026-07-01
NTI164Placebo
Breast CancerBladder CancerKidney Cancer

Germline Alterations of Tumor Susceptibility Genes in New York Cancer Patients

ACTIVE NOT RECRUITING
NCT00579514Phase NAMemorial Sloan Kettering Cancer CenterStarted 2000-03
PCR/PCR/LDR Strategy
Non-Allergic Rhinitis With Eosinophilia Syndrome

Efficacy and Safety of Stapokibart in Non-Allergic Rhinitis With Eosinophilia Syndrome

NOT YET RECRUITING
NCT07240376Phase NAHuazhong University of Science and TechnologyStarted 2025-11-25
Stapokibart (CM310)Placebo
Alcohol Use DisorderRisk Behavior, HealthDysbiosis

Alcohol Misuse, Gut Microbial Dysbiosis and PrEP Care Continuum: Application and Efficacy of SBIRT Intervention

RECRUITING
NCT06005298Phase NAShirish S BarveStarted 2023-08-01
Screening, Brief Intervention, Referral to Treatment (SBIRT)

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