ACKR4

Chr 3

atypical chemokine receptor 4

Also known as: CC-CKR-11, CCBP2, CCR-11, CCR10, CCR11, CCRL1, CCX CKR, CCX-CKR

The protein encoded by this gene is a member of the G protein-coupled receptor family, and is a receptor for C-C type chemokines. This receptor has been shown to bind dendritic cell- and T cell-activated chemokines including CCL19/ELC, CCL21/SLC, and CCL25/TECK. A pseudogene of this gene is found on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2013]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.80
Clinical SummaryACKR4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
4 VUS of 6 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.80LOEUF
pLI 0.000
Z-score -0.55
OE 1.19 (0.761.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.84Z-score
OE missense 0.82 (0.720.94)
147 obs / 178.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?1.19 (0.761.80)
00.351.4
Missense OE?0.82 (0.720.94)
00.61.4
Synonymous OE?0.99
01.21.6
LoF obs/exp: 12 / 10.1Missense obs/exp: 147 / 178.7Syn Z: 0.05

This gene — mechanism propensity

DN
0.75top 25%
GOF
0.7029th %ile
LOF
0.2483th %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

6 submitted variants in ClinVar

Classification Summary

VUS4
Likely Benign1
4
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
4
0
0
4
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total04015

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap ACKR4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

ACKR4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →