mutations in epas1 gene are related to early onset of neuroendocrine tumors such as paragangliomas, somatostatinomas and/or pheochromocytomas. the mutations are commonly somatic missense mutations that locate in the primary hydroxylation site of hif-2α, which disrupt the protein hydroxylation/degradation mechanism, and leads to protein stabilization and pseudohypoxic signaling. in addition, these neuroendocrine tumors release erythropoietin (epo) into circulating blood, and lead to polycythemia.