Molecular basis of familial erythrocytosis. Four types are shown, resulting from loss-of-function (LoF) or gain-of-function (GoF) missense mutations in the genes encoding EPOR (type 1), VHL (type 2), PHD2 (type 3), and HIF-2α (type 4), respectively. Note that the symbols for the genes encoding PHD2 and HIF-2α are EGLN1 and EPAS1, respectively. The familial erythrocytoses are inherited as autosomal-dominant traits, except for type 2 (Chuvash polycythemia), which displays autosomal-recessive inheritance. A variety of mutations that result in a truncated and constitutively active EPOR have been reported as the cause of type 1 familial erythrocytosis.