ACKR1 is the approved gene symbol for DARC, the Duffy Antigen Receptor for Chemokines.
ACKR1 encodes for the Duffy blood group antigen, also called Fy glycoprotein (FY) or CD234 (Cluster of Differentiation 234). There are 2 major codominant alleles: FY*A and FY*B, encoded by rs12075, resulting in the common phenotypes: Fy(a+b+), Fy(a+b-), and Fy(a-b+). Frequencies for these three phenotypes vary but one source cites the following:
- Fy(a+b+): 49% Caucasians, 1% Blacks, 9% Chinese
- Fy(a-b+): 34% Caucasians, 22% Blacks, <1% Chinese
- Fy(a+b-): 17% Caucasians, 9% Blacks, 91% Chinese
In the promoter region of the ACKR1 gene, at rs2814778, a variant exists that abolishes all Duffy antigen. As a result, individuals who are homozygous for this variant and therefore have the rs2814778(G;G) genotype have the Fy(a-b-) phenotype. Also known as the Duffy null phenotype, Fy(a-b-) is very rare in Caucasians but is found in 68% of Blacks.
Duffy antigens have many significant clinical roles. Infection resistance, in particular to malaria, is the most noted, but there are important autoimmunity effects.