CCL3L3

Chr 17

C-C motif chemokine ligand 3 like 3

Also known as: 464.2, D17S1718, G0S19-2, LD78, LD78BETA, SCYA3L, SCYA3L1

NCBI Gene: 414062ENSG00000276085UniProt: P16619

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]

0
Active trials
45
ClinVar variants
32
Pathogenic / LP
0.3
Missense Z
1.86
LOEUF
5
Pubs (2 yr)
Clinical Summary— CCL3L3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 5 VUS of 45 total submissions

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.
1.86LOEUF
pLI 0.315
Z-score 0.52
OE 0.00 (0.00–1.86)
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.
0.31Z-score
OE missense 0.60 (0.27–1.50)
3 obs / 5.0 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 (0.00–1.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.27–1.50)
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.0.48
0≤1.21.6
LoF obs/exp: 0 / 0.3Missense obs/exp: 3 / 5.0Syn Z: 0.59

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic3
VUS5
Likely Benign6
Benign2
29
Pathogenic
3
Likely Pathogenic
5
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
3
0
3
VUS
0
4
1
0
5
Likely Benign
0
1
5
0
6
Benign
0
0
2
0
2
Total0540045

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

View in ClinVar →

Protein Context — Lollipop Plot

CCL3L3 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deciphering distinct pathogenic mechanisms of ankylosing spondylitis and systemic sclerosis via shared biomarkers ZSWIM6 and CCL3L3: Insights from an integrative bioinformatics approach.
Huang L et al.·Autoimmunity
2025Functional
ScRNA-seq and bulk RNA-seq identified NUPR1 as novel biomarkers related to CD4 + T cells infiltration for abdominal aortic aneurysm.
Zhou Z et al.·Mol Biol Rep
2024
Population-wide copy number variation calling using variant call format files from 6,898 individuals.
Png G et al.·Genet Epidemiol
2020
Distribution and prognostic impact of microglia/macrophage subpopulations in gliomas.
Zeiner PS et al.·Brain Pathol
2019
Identification of Inflammation-Related Biomarker Pro-ADM for Male Patients With Gout by Comprehensive Analysis.
Qiu K et al.·Front Immunol
2022Cohort
Transcriptome Analysis of Host Inflammatory Responses to the Ectoparasitic Mite Sarcoptes scabiei var. hominis.
Shehwana H et al.·Front Immunol
2021
African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors associated with immunologic functions and environmental exposures.
Singh U et al.·Sci Rep
2021
Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes.
Yeo AS et al.·PLoS One
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Chlamydia trachomatis Stimulation Enhances HIV-1 Susceptibility through the Modulation of a Member of the Macrophage Inflammatory Proteins.
Dzakah EE et al.·J Invest Dermatol
2022
Establishing a Ten Disulfidptosis-related Gene Signature for Prognostic Prediction in Skin Cutaneous Melanoma.
Li H et al.·Comb Chem High Throughput Screen
2024
Pulmonary exposure to renewable diesel exhaust particles alters protein expression and toxicity profiles in bronchoalveolar lavage fluid and plasma of mice
McCarrick S et al.·Arch Toxicol
2024
Gene expression profile and long noncoding RNA analysis in Candida albicans insoluble beta-glucan-stimulated CD14+ monocytes and THP-1 cells.
Hou JS et al.·Microb Pathog
2021
Identification of biomarkers, pathways and potential therapeutic agents for salt-sensitive hypertension using RNA-seq
Chao X et al.·Front Cardiovasc Med
2022
Profile for mRNA transcript abundances in the pig endometrium where inflammation was induced by Escherichia coli.
Jana B et al.·Anim Reprod Sci
2021
Seasonal Influences on Human Placental Transcriptomes Associated with Spontaneous Preterm Birth
Akram KM et al.·Cells
2025
Top 7 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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