CCL20

Chr 2

C-C motif chemokine ligand 20

Also known as: CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A, SCYA20, ST38

NCBI Gene: 6364 ENSG00000115009 UniProt: P78556 OMIM: 601960

The protein CCL20 is a chemokine that binds to receptor CCR6 to attract immune cells including dendritic cells, T-cells, and B-cells to sites of inflammation and mucosal surfaces, and also exhibits antimicrobial activity against bacteria. This gene is not highly constrained against loss-of-function mutations (pLI = 0.0002, LOEUF = 1.875) and is not currently associated with established Mendelian disease phenotypes in pediatric patients.

OMIM ResearchSummary from RefSeq, UniProt

This antimicrobial gene belongs to the subfamily of small cytokine CC genes. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The protein encoded by this gene displays chemotactic activity for lymphocytes and can repress proliferation of myeloid progenitors. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

Active trials

480

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.000

Z-score -0.31

OE 1.16 (0.58–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.59Z-score

OE missense 0.78 (0.61–1.00)

43 obs / 55.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.16 (0.58–1.88)

0≤0.351.4

Missense OE?0.78 (0.61–1.00)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 5 / 4.3Missense obs/exp: 43 / 55.3Syn Z: 0.57

Background carrier burden — how many people carry a rare variant somewhere in CCL20?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 660

113 rare PASS variants

Rare truncating (LoF)

1 in 8,500

28 rare PASS variants

Rare synonymous (reference)

1 in 900

41 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCL20. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 1,000	1 in 9,000
South Asian	~43k	1 in 200	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 450	≈ 1 in 9,400
European (Finnish)	~27k	1 in 2,700	1 in 4,300
Admixed American	~22k	1 in 540	1 in 3,700
African / African American	~21k	1 in 520	≈ 1 in 5,400
East Asian	~20k	1 in 600	1 in 2,600
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 4 coding exons well covered in gnomAD exomes; exons 2, 3, 4 marginal. Genomes: all 4.? see exons ↓