CCL8

Chr 17

C-C motif chemokine ligand 8

Also known as: HC14, MCP-2, MCP2, SCYA10, SCYA8

NCBI Gene: 6355 ENSG00000108700 UniProt: P80075

This antimicrobial gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes, lymphocytes, basophils and eosinophils. By recruiting leukocytes to sites of inflammation this cytokine may contribute to tumor-associated leukocyte infiltration and to the antiviral state against HIV infection. [provided by RefSeq, Sep 2014]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

0.1

Missense Z

1.75

LOEUF

Clinical Summary— CCL8

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 Pathogenic / Likely Pathogenic· 22 VUS of 35 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Some data sources returned errors (1)

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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.

1.75LOEUF

pLI 0.041

Z-score 0.50

OE 0.69 (0.27–1.75)

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.

0.13Z-score

OE missense 0.95 (0.76–1.20)

50 obs / 52.7 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.0.69 (0.27–1.75)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.76–1.20)

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.1.68

0≤1.21.6

LoF obs/exp: 2 / 2.9Missense obs/exp: 50 / 52.7Syn Z: -2.33

0.76top 25%

GOF

0.4381th %ile

LOF

0.2091th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.