Two new mutations in the HIF2A gene associated with erythrocytosis
Open accessAbstract
Abstract Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen‐sensing pathway that regulates the Erythropoietin (EPO) gene. More specifically, recent studies have identified erythrocytosis‐associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor‐2α (HIF‐2α), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met‐535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe‐540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF‐2α with both VHL and PHD2. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
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Most gain-of-function mutations in HIF-2α are in direct proximity to proline residue 531.
“Most gain-of-function mutations in HIF-2α are in direct proximity to proline residue 531, which is one of the two main hydroxylation sites (the other major hydroxylation site is proline 405). 147–154”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [154]
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Regulation of erythropoiesis by hypoxia-inducible factors
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- Authors
- Percy, M. J., Chung, Y. J., Harrison, C., Mercieca, J., Hoffbrand, A. V., Dinardo, C. L., Santos, P. C. J. L., Fonseca, G. H. H., Gualandro, S. F. M., Pereira, A. C., Lappin, T. R. J., McMullin, M. F., & Lee, F. S.
- Affiliations
- Belfast City Hospital (GB)
- University of Pennsylvania (US)
- St Thomas' Hospital (GB)
- St Helier Hospital (GB)
- The Royal Free Hospital (GB)
- Universidade de São Paulo (BR)
- Queen's University Belfast (GB)
- Corresponding author
- Lee, Frank S.
- ORCID
- Venue
- American Journal of Hematology
- Publisher
- Wiley
- Published
- 2012-02-24
- Volume
- 87
- Issue
- 4
- Pages
- 439-442
- ISSN
- 0361-8609 (ISSN-L)
- 1096-8652
- PMC
- PMC3399664
- OpenAlex
- W1985535116
- Cited by
- 37
- References
- 25
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 8
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Hematology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Universidade de São Paulo
- National Cancer Institute (R01CA153347)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- HIF-2α, erythrocytosis, familial erythrocytosis, missense mutations, PHD2, von Hippel-Lindau protein, protein-protein interaction, oxygen sensing, erythropoietin regulation, polycythemia
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Adult, Amino Acid Sequence, Base Sequence, Erythropoietin, Exons, Female, Heterozygote, Humans, Male, Middle Aged, Molecular Sequence Data, Polycythemia, Procollagen-Proline Dioxygenase, Signal Transduction, Sequence Alignment, Conserved Sequence, Point Mutation, Sequence Homology, Amino Acid, Amino Acid Substitution, Mutation, Missense, Protein Interaction Mapping, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor-Proline Dioxygenases
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