title: A gain-of-function mutation in the HIF2A gene in familial erythrocytosis.
abstract: Hypoxia-inducible factor (HIF) alpha, which has three isoforms, is central to the continuous balancing of the supply and demand of oxygen throughout the body. HIF-alpha is a transcription factor that modulates a wide range of processes, including erythropoiesis, angiogenesis, and cellular metabolism. We describe a family with erythrocytosis and a mutation in the HIF2A gene, which encodes the HIF-2alpha protein. Our functional studies indicate that this mutation leads to stabilization of the HIF-2alpha protein and suggest that wild-type HIF-2alpha regulates erythropoietin production in adults.
authors.affiliation: Belfast City Hospital, Northern Ireland, United Kingdom. melanie.percy@belfasttrust.hscni.net
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Percy
authors.forename: Paul W
authors.initials: PW
authors.lastname: Furlow
authors.forename: Guy S
authors.initials: GS
authors.lastname: Lucas
authors.forename: Xiping
authors.initials: X
authors.lastname: Li
authors.forename: Terence R J
authors.initials: TR
authors.lastname: Lappin
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: McMullin
authors.forename: Frank S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004920:Erythropoiesis / Q000235:genetics*; D004921:Erythropoietin / Q000096:biosynthesis*; D005260:Female; D005838:Genotype; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011086:Polycythemia / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004921:Erythropoietin; D006454:Hemoglobins; D000099162:Endothelial PAS Domain-Containing Protein 1