CCL21

Chr 9

C-C motif chemokine ligand 21

Also known as: 6Ckine, CKb9, ECL, SCYA21, SLC, TCA4

NCBI Gene: 6366ENSG00000137077UniProt: O00585

This antimicrobial gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. Similar to other chemokines the protein encoded by this gene inhibits hemopoiesis and stimulates chemotaxis. This protein is chemotactic in vitro for thymocytes and activated T cells, but not for B cells, macrophages, or neutrophils. The cytokine encoded by this gene may also play a role in mediating homing of lymphocytes to secondary lymphoid organs. It is a high affinity functional ligand for chemokine receptor 7 that is expressed on T and B lymphocytes and a known receptor for another member of the cytokine family (small inducible cytokine A19). [provided by RefSeq, Sep 2014]

101
ClinVar variants
70
Pathogenic / LP
0.04
pLI score
3
Active trials
Clinical Summary— CCL21
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
70 Pathogenic / Likely Pathogenic· 26 VUS of 101 total submissions
💊
Clinical Trials
3 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?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.
1.21LOEUF
pLI 0.036
Z-score 1.24
OE 0.47 (0.21–1.21)
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.
0.12Z-score
OE missense 0.96 (0.80–1.17)
73 obs / 75.9 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.0.47 (0.21–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.80–1.17)
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.0.99
0≤1.21.6
LoF obs/exp: 3 / 6.4Missense obs/exp: 73 / 75.9Syn Z: 0.06

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic8
VUS26
Likely Benign2
Benign1
62
Pathogenic
8
Likely Pathogenic
26
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
8
0
8
VUS
0
14
12
0
26
Likely Benign
0
2
0
0
2
Benign
0
0
0
1
1
Total01682199

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

View in ClinVar →

Protein Context — Lollipop Plot

CCL21 · 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
CXCL10 and CCL21 Promote Migration of Pancreatic Cancer Cells Toward Sensory Neurons and Neural Remodeling in Tumors in Mice, Associated With Pain in Patients.
Hirth M et al.·Gastroenterology
2020Cohort
Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment.
Wang YF et al.·Theranostics
2022
Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation.
Wang X et al.·Nat Commun
2025
Tertiary lymphoid structures as a biomarker in immunotherapy and beyond: Advancing towards clinical application.
Cui X et al.·Cancer Lett
2025Review
Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.
Mastini C et al.·Sci Transl Med
2023
Tertiary lymphoid organs are associated with the progression of kidney damage and regulated by interleukin-17A.
Luo R et al.·Theranostics
2021
Enhancing Th17 cells drainage through meningeal lymphatic vessels alleviate neuroinflammation after subarachnoid hemorrhage.
Gao D et al.·J Neuroinflammation
2024
The pathogenic importance of CCL21 and CCR7 in rheumatoid arthritis.
Van Raemdonck K et al.·Cytokine Growth Factor Rev
2020Review
Baseline Serum and Stool Microbiome Biomarkers Predict Clinical Efficacy and Tissue Molecular Response After Ritlecitinib Induction Therapy in Ulcerative Colitis.
Hassan-Zahraee M et al.·J Crohns Colitis
2024Clinical trial
CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.
Salehi-Rad R et al.·J Immunother Cancer
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Prostate CancerProstate Inflammation

Characterization of Microbiological and Genetic Features in Prostate Cancer and Their Association with Disease Stage

ENROLLING BY INVITATION
NCT06505356Phase NAEdgaras BurzinskisStarted 2024-09-01
Prostate biopsy
Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8Stage IVA Lung Cancer AJCC v8

CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer

ACTIVE NOT RECRUITING
NCT03546361Phase PHASE1Jonsson Comprehensive Cancer CenterStarted 2019-07-08
Autologous Dendritic Cell-Adenovirus CCL21 VaccinePembrolizumab
Scarring Alopecia

Non-Ablative Laser to Treat Scarring Alopecia With Hair Follicle Gene Expression Analysis

RECRUITING
NCT06946550Phase NAMontefiore Medical CenterStarted 2025-12-09
1470nm non-ablative fractional laser

External Resources

Links to major genomics databases and tools