CCR8

Chr 3

C-C motif chemokine receptor 8

Also known as: CC-CKR-8, CCR-8, CDw198, CKRL1, CMKBR8, CMKBRL2, CY6, GPRCY6

This G protein-coupled receptor binds various chemokines including CCL1, CCL8, CCL16, and CCL18 to regulate monocyte and eosinophil chemotaxis, T cell positioning, and microglial phagocytosis. CCR8 mutations cause primary immunodeficiency with recurrent infections and follows an autosomal recessive inheritance pattern. The gene shows low constraint to loss-of-function variants, which is consistent with recessive disease.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.33
Clinical SummaryCCR8
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 43 VUS of 60 total submissions
Some data sources returned errors (1)

opentargets: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.008
Z-score 1.00
OE 0.59 (0.291.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.24Z-score
OE missense 0.95 (0.841.08)
172 obs / 181.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.291.33)
00.351.4
Missense OE0.95 (0.841.08)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 4 / 6.8Missense obs/exp: 172 / 181.2Syn Z: 0.09
DN
0.84top 10%
GOF
0.77top 25%
LOF
0.1895th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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.

ClinVar Variant Classifications

60 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS43
Likely Benign4
8
Pathogenic
1
Likely Pathogenic
43
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
42
1
0
43
Likely Benign
0
2
2
0
4
Benign
0
0
0
0
0
Total04412056

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

View in ClinVar →

Protein Context — Lollipop Plot

CCR8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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