CCL22

Chr 16

C-C motif chemokine ligand 22

Also known as: A-152E5.1, ABCD-1, DC/B-CK, MDC, SCYA22, STCP-1

NCBI Gene: 6367 ENSG00000102962 UniProt: O00626 OMIM: 602957

The protein encoded by this gene is a chemokine that attracts monocytes, dendritic cells, natural killer cells, and activated T lymphocytes to inflammatory sites by binding to the CCR4 receptor. The gene shows low constraint to loss-of-function variation (pLI = 0.008, LOEUF = 1.8), suggesting it may tolerate complete loss of function. No established Mendelian diseases have been associated with CCL22 mutations in current databases.

OMIM ResearchSummary from RefSeq, UniProt

This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for monocytes, dendritic cells, natural killer cells and for chronically activated T lymphocytes. It also displays a mild activity for primary activated T lymphocytes and has no chemoattractant activity for neutrophils, eosinophils and resting T lymphocytes. The product of this gene binds to chemokine receptor CCR4. This chemokine may play a role in the trafficking of activated T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

Active trials

194

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.80

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.80LOEUF

pLI 0.008

Z-score 0.22

OE 0.87 (0.38–1.80)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.45Z-score

OE missense 0.84 (0.67–1.06)

53 obs / 63.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.38–1.80)

0≤0.351.4

Missense OE?0.84 (0.67–1.06)

0≤0.61.4

Synonymous OE?1.43

0≤1.21.6

LoF obs/exp: 3 / 3.4Missense obs/exp: 53 / 63.1Syn Z: -1.68

Background carrier burden — how many people carry a rare variant somewhere in CCL22?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 410

123 rare PASS variants

Rare truncating (LoF)

1 in 5,700

20 rare PASS variants

Rare synonymous (reference)

1 in 1,000

58 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCL22. 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 420	1 in 4,600
South Asian	~43k	1 in 370	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 430	1 in 4,300
European (Finnish)	~27k	1 in 1,700	none seen
Admixed American	~22k	1 in 500	1 in 1,600
African / African American	~21k	1 in 200	none seen
East Asian	~20k	1 in 620	none seen
Ashkenazi Jewish	~13k	1 in 2,200	none seen
Middle Eastern	~2,884	1 in 480	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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓