Important chemokine system mutations strongly associated with human disease
| Molecule | Mutation | Disease | Phenotype | Mechanism |
|---|---|---|---|---|
| CCR5 | CCR5Δ32 (loss of function) | HIV/AIDS | Resistance to initial infection (−/−) | Loss of HIV coreceptor CCR5 prevents cell entry by R5-tropic HIV-1 |
| Delayed disease progression (+/−) | ||||
| West Nile virus infection | Increased risk of symptomatic infection (−/−) | Reduced leukocyte trafficking to brain | ||
| Rheumatoid arthritis | Reduced risk (+/−) | Reduced inflammation | ||
| Chronic renal allograft rejection | Reduced risk (−/−) | Reduced inflammation | ||
| CXCR4 | C-tail truncations (gain of function) | WHIM Syndrome | Warts | Impaired egress of leukocytes from bone marrow |
| Hypoglobulinemia | ||||
| Infections | ||||
| Myelokathexis (Mendelian AD) | ||||
| CX3CR1 | CX3CR1-M280 | Cardiovascular disease | Reduced risk (+/−) | Reduced foam cell accumulation in vessel wall |
| Age-related macular degeneration | Increased risk (+/−) | Microglial cell accumulation in the subretinal space | ||
| ACKR1 | FYB(ES) (loss of function) | Plasmodium vivax malaria | Resistance to initial infection (−/−) | Promoter mutation abolishes RBC expression of ACKR1, which is required for cell entry by P. vivax |
| CCL26 | CCL26 GG | Eosinophilic esophagitis | Increased risk (GG) | CCR3-dependent eosinophil trafficking |
−/−, Homozygous; +/−, heterozygous; AD, autosomal dominant; GG, genotype GG; RBC, red blood cell.