Polymorphisms in the PAR4 gene (f2rl3) give rise to sequence variants that have altered reactivities. (A) PAR4-120T is hyperreactive compared with PAR4-120A. The rare PAR4 variant, PAR4-296V, has low reactivity regardless of the amino acid at 120. (B) Individuals heterozygous for PAR4-296V have low PAR4 reactivity and subsequent low platelet response to PAR4 agonists. A potential mechanism is that the hyporeactive allele sequesters the hyperreactive allele as a dominant-negative receptor.