The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis
Open accessAbstract
Erythrocytosis can arise from deregulation of the erythropoietin (Epo) axis resulting from defects in the oxygen-sensing pathway. Epo synthesis is controlled by the hypoxia inducible factor (HIF) complex, composed of an alpha and a beta subunit. There are 2 main alpha subunits, HIF-1 alpha and HIF-2 alpha. Recently, a HIF-2 alpha Gly537Trp mutation was identified in a family with erythrocytosis. This raises the possibility of HIF2A mutations being associated with other cases of erythrocytosis. We now report a subsequent analysis of HIF2A in a cohort of 75 erythrocytosis patients and identify 4 additional patients with novel heterozygous Met535Val and Gly537Arg mutations. All patients presented at a young age with elevated serum Epo. Mutations at Gly-537 account for 4 of 5 HIF2A mutations associated with erythrocytosis. These findings support the importance of HIF-2 alpha in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis.
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“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 [148]
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Self-citationStructure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling
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Metadata
- Authors
- Percy, M. J., Beer, P. A., Campbell, G., Dekker, A. W., Green, A. R., Oscier, D., Rainey, M. G., van Wijk, R., Wood, M., Lappin, T. R. J., McMullin, M. F., & Lee, F. S.
- Affiliations
- Belfast City Hospital (GB)
- University of Cambridge (GB)
- National Health Service (GB)
- University Medical Center Utrecht (NL)
- Royal Bournemouth Hospital (GB)
- Vale of Leven District General Hospital (GB)
- Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands;
- Queen's University Belfast (GB)
- University of Pennsylvania (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2008-06-01
- Volume
- 111
- Issue
- 11
- Pages
- 5400-5402
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2396730
- OpenAlex
- W2028331311
- Cited by
- 127
- References
- 21
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 7 · 2023: 6 · 2022: 3 · 2021: 8 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 11 · 2015: 4 · 2014: 9 · 2013: 18 · 2012: 4
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Cancer Research UK
- National Institutes of Health
- National Cancer Institute (R01CA090261)
- 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 (clinical) › Hemoglobinopathies and Related Disorders
- Keywords
- erythrocytosis, HIF-2α, erythropoietin regulation, hypoxia-inducible factor, HIF-1α, oxygen sensing, serum erythropoietin
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Adolescent, Adult, Base Sequence, DNA Mutational Analysis, Erythropoietin, Female, Humans, Male, Molecular Sequence Data, Mutation, Polycythemia, Polymerase Chain Reaction, Basic Helix-Loop-Helix Proteins
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