ACKR3
Chr 2ARatypical chemokine receptor 3
Also known as: CMKOR1, CXC-R7, CXCR-7, CXCR7, GPR159, RDC-1, RDC1
ACKR3 encodes an atypical chemokine receptor that regulates chemokine levels through high-affinity binding and internalization, and controls axon guidance in the oculomotor system by regulating CXCL12 levels. Mutations cause oculomotor-abducens synkinesis with autosomal recessive inheritance. This gene has moderate constraint against loss-of-function variants (LOEUF 0.68).
Primary Disease Associations & Inheritance
Some data sources returned errors (1)
gnomad: TimeoutError: The operation was aborted due to timeout
Population Genetics & Constraint
Constraint data not available from gnomAD.
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
128 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 68 | 0 | 69 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 35 | 8 | 0 | 43 |
Likely Benign | 0 | 4 | 5 | 0 | 9 |
Benign | 0 | 1 | 0 | 2 | 3 |
Conflicting | — | 1 | |||
| Total | 0 | 41 | 82 | 2 | 126 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ACKR3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools