| HGNC Family | Chemokine ligands (CCL) |
| Name | chemokine (C-C motif) ligand 3-like 3 |
| Description | This gene is one of several cytokine genes that are clustered on the q-arm of chromosome 17. Cytokines are a family of secreted proteins that function in inflammatory and immunoregulatory processes. The protein encoded by this gene binds to several chemokine receptors, including chemokine binding protein 2 and chemokine (C-C motif) receptor 5 (CCR5). CCR5 is a co-receptor for HIV, and binding of this protein to CCR5 inhibits HIV entry. The copy number of this gene varies among individuals, where most individuals have one to six copies, and a minority of individuals have zero or more than six copies. There are conflicting reports about copy number variation of this gene and its correlation to disease susceptibility.[provided by RefSeq, Apr 2014] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The chemokine gene family member CCL3L3—one of several highly similar, copy‐number–variable genes at the 17q12 locus encoding proteins related to macrophage inflammatory protein 1–α (MIP‑1α)—plays an important role in host immune defense. Its protein product binds to the chemokine receptor CCR5, thereby participating in innate and adaptive immune responses by promoting immune cell chemotaxis and modulating T‐cell activation. In addition, by engaging CCR5, the chemokine exerts potent anti–HIV‐1 activity through competitive inhibition of viral entry, and variations in its genomic dosage have been linked to differences in HIV‐1 susceptibility and disease progression. In various studies, individuals with a lower gene copy number (and hence lower levels of secreted chemokine) were found to have an increased risk of HIV‐1 infection and more rapid progression to AIDS, whereas higher copy numbers appear to correlate with more robust HIV‐suppressive responses (see, for example."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its antiviral role, the balance of CCL3L3, together with related chemokine genes (such as CCL3, CCL4, and CCL4L1), is emerging as a determinant of inflammatory tone. Elevated gene dosage may enhance chemokine‐mediated inflammatory responses and has been associated with autoimmune conditions such as rheumatoid arthritis and type 1 diabetes—especially when interacting with variants in the CCR5 gene—thereby influencing susceptibility to and severity of autoimmunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, detailed analyses of the genomic architecture of this chemokine cluster indicate that not only the total copy number but also the relative proportion of distinct gene components (for example, those producing classical versus alternatively spliced transcripts) can differentially affect immune modulation and disease risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CCL3L3 functions as a key mediator of host defense by modulating leukocyte recruitment and T‐cell activation, inhibiting HIV‐1 entry via its interaction with CCR5, and influencing inflammatory responses that can contribute to autoimmunity. The range of copy number variation within this gene provides a genetic basis for the diverse immune responses observed in individuals, linking both resistance to viral infection and susceptibility to immune‐mediated disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Enrique Gonzalez, Hemant Kulkarni, Hector Bolivar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1101160"}], "href": "https://doi.org/10.1126/science.1101160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15637236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15637236"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Matthew J Dolan, Hemant Kulkarni, Jose F Camargo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1521"}], "href": "https://doi.org/10.1038/ni1521"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17952079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17952079"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sharon Shalekoff, Stephen Meddows-Taylor, Diana B Schramm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Host CCL3L1 gene copy number in relation to HIV-1-specific CD4+ and CD8+ T-cell responses and viral load in South African women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Acquir Immune Defic Syndr (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/QAI.0b013e31816fdc77"}], "href": "https://doi.org/10.1097/QAI.0b013e31816fdc77"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18360285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18360285"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "SiJie Liu, Lei Yao, DongLin Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCL3L1 copy number variation and susceptibility to HIV-1 infection: a meta-analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0015778"}], "href": "https://doi.org/10.1371/journal.pone.0015778"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21209899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21209899"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "C McKinney, M E Merriman, P T Chapman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Rheum Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/ard.2007.075028"}], "href": "https://doi.org/10.1136/ard.2007.075028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17604289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17604289"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M Mamtani, J-M Anaya, W He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2009.71"}], "href": "https://doi.org/10.1038/gene.2009.71"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19741716"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19741716"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "W Shao, J Tang, W Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCL3L1 and CCL4L1: variable gene copy number in adolescents with and without human immunodeficiency virus type 1 (HIV-1) infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.gene.6364378"}], "href": "https://doi.org/10.1038/sj.gene.6364378"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17330138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17330138"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ludmila Shostakovich-Koretskaya, Gabriel Catano, Zoya A Chykarenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combinatorial content of CCL3L and CCL4L gene copy numbers influence HIV-AIDS susceptibility in Ukrainian children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "AIDS (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/QAD.0b013e3283270b3f"}], "href": "https://doi.org/10.1097/QAD.0b013e3283270b3f"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19279442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19279442"}]}]}]}
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| Synonyms | 464.2 |
| NCBI Gene ID | 414062 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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CCL3L3 has 1,610 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 49 datasets.
Click the + buttons to view associations for CCL3L3 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of CCL3L3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of CCL3L3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of CCL3L3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of CCL3L3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of CCL3L3 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of CCL3L3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of CCL3L3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of CCL3L3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of CCL3L3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| CTD Gene-Disease Associations | diseases associated with CCL3L3 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by CCL3L3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with CCL3L3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of CCL3L3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of CCL3L3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with CCL3L3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing CCL3L3 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of CCL3L3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of CCL3L3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of CCL3L3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of CCL3L3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of CCL3L3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of CCL3L3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of CCL3L3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of CCL3L3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with CCL3L3 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of CCL3L3 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of CCL3L3 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with CCL3L3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by CCL3L3 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for CCL3L3 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of CCL3L3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of CCL3L3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways 2026 | pathways involving CCL3L3 protein from the KEGG Pathways 2026 dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of CCL3L3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of CCL3L3 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain CCL3L3 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by CCL3L3 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MiRTarBase microRNA Targets | microRNAs targeting CCL3L3 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of CCL3L3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by CCL3L3 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of CCL3L3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving CCL3L3 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving CCL3L3 protein from the Wikipathways PFOCR 2024 dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of CCL3L3 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of CCL3L3 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of CCL3L3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of CCL3L3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| WikiPathways Pathways 2014 | pathways involving CCL3L3 protein from the Wikipathways Pathways 2014 dataset. | |
| WikiPathways Pathways 2024 | pathways involving CCL3L3 protein from the WikiPathways Pathways 2024 dataset. | |
