ACKR1 (Atypical Chemokine Receptor 1): Gene, Function, and Clinical Significance
A comprehensive overview of the ACKR1 gene, its protein product, expression patterns, associated diseases, and mutations.
Gene Information Card
| Symbol | ACKR1 |
|---|---|
| Full Name | Atypical Chemokine Receptor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 1q23.2 |
| NCBI Gene ID | 2532 ncbi.nlm.nih.gov/gene/2532 |
| Ensembl ID | ENSG00000120688 |
| UniProt ID | Q16570 |
| OMIM ID | 613665 |
| HGNC ID | 16572 |
| Aliases | DARC, FY, GPD, CCBP1, CD234, Duffy blood group antigen |
Description
ACKR1 (Atypical Chemokine Receptor 1), also known as Duffy antigen receptor for chemokines (DARC), is a seven-transmembrane protein that binds various chemokines but does not signal through G proteins. It is expressed on erythrocytes, endothelial cells, and other tissues, playing roles in chemokine clearance, inflammation modulation, and malaria susceptibility. The gene also determines the Duffy blood group system.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Malaria (Plasmodium vivax) | ACKR1 on erythrocytes serves as the entry receptor for P. vivax; Duffy-negative individuals are resistant. | OMIM 613665; PubMed studies |
| Duffy blood group incompatibility | Antigenic variants (FY*A, FY*B) can cause transfusion reactions or hemolytic disease of the newborn. | OMIM 110700 (Duffy blood group) |
| Inflammatory diseases (e.g., asthma, atherosclerosis) | ACKR1 modulates chemokine levels, influencing leukocyte recruitment and inflammation. | PubMed; ClinVar |
| HIV infection | ACKR1 may influence HIV susceptibility or progression via chemokine interactions. | PubMed; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 0.0 | Not detected |
| Bone Marrow | 0.0 | Not detected |
| Brain | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Vasculature | High | Endothelial cells (not in GTEx) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Erythrocytes | N/A | High expression; not in GTEx |
| Endothelial cells | N/A | High expression; not in GTEx |
| HEK293 | 0.0 | Not expressed |
| HeLa | 0.0 | Not expressed |
| K562 | 0.0 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2814778 (GATA box mutation) | SNP (promoter) | High in African populations (Duffy-negative allele) | Disrupts erythroid expression; confers resistance to P. vivax malaria |
| FY*A (Gly42Asp) | Missense | Common in many populations | Alters antigenicity; no known functional effect on chemokine binding |
| FY*B (Gly42Asp) | Missense | Common | Same as FY*A; antigenic variant |
| Other rare variants | Various | Rare | Potential effects on expression or binding; limited data |
Mutation functional classification
Loss of Function (LOF)
The Duffy-null allele (rs2814778) causes loss of erythroid expression, leading to loss of chemokine clearance on red blood cells and resistance to P. vivax malaria.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may alter binding affinity but not signaling.
Dominant Negative (DN)
Not applicable; ACKR1 is not known to form dominant-negative interactions.
View complete mutation data：
Gene Ontology (GO)
| • chemokine binding | • chemokine receptor activity |
| • G protein-coupled receptor activity | • plasma membrane |
| • integral component of membrane | • inflammatory response |
| • chemokine-mediated signaling pathway | • cell surface receptor signaling pathway |
Pathways
• Chemokine signaling pathway (hsa04062)
• Cytokine-cytokine receptor interaction (hsa04060)
• Malaria (hsa05144)
Protein Summary
ACKR1 is a seven-transmembrane protein that binds multiple inflammatory chemokines (e.g., CXCL8, CCL2, CCL5) with high affinity but does not activate G protein signaling. It acts as a 'chemokine sink' or scavenger, regulating chemokine availability and leukocyte migration. On erythrocytes, it is the Duffy blood group antigen and the receptor for Plasmodium vivax invasion. It is also expressed on endothelial cells, where it may facilitate chemokine transcytosis. The protein is a member of the atypical chemokine receptor family.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACKR1 Knockout HEK293 Cell Line | EDJ-KQ4647 | Human | 2532 | Details Get a Quote |
| ACKR1 Knockout HeLa Cell Line | EDJ-KQ53281 | Human | 2532 | Details Get a Quote |
| ACKR1 Knockout A-549 Cell Line | EDJ-KQ61763 | Human | 2532 | Details Get a Quote |
| ACKR1 Knockout HCT 116 Cell Line | EDJ-KQ70245 | Human | 2532 | Details Get a Quote |
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