A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove
Open accessAbstract
The molecular basis of the erythrocytosis group of red cell disorders is incompletely defined. Some cases are due to dysregulation of erythropoietin (Epo) synthesis. The hypoxia inducible transcription factor (HIF) tightly regulates Epo synthesis. HIF in turn is regulated through its alpha subunit, which under normoxic conditions is hydroxylated on specific prolines and targeted for degradation by the von Hippel Lindau (VHL) protein. Several mutations in VHL have been reported in erythrocytosis, but only 1 mutation in the HIF prolyl hydroxylase PHD2 (prolyl hydroxylase domain protein 2) has been described. Here, we report a novel PHD2 mutation, Arg371His, which causes decreased HIF binding, HIF hydroxylase, and HIF inhibitory activities. In the tertiary structure of PHD2, Arg371 lies close to the previously described Pro317Arg mutation site. These findings substantiate PHD2 as a critical enzyme controlling HIF and therefore Epo in humans, and furthermore suggest the location of an active site groove in PHD2 that binds HIF.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Patients heterozygous for PHD2 mutations are characterized by increased red blood cell values with inappropriately normal serum EPO levels.
“Patients, who were heterozygous for these mutations were characterized by increased rbc values in the presence of inappropriately normal serum EPO levels. 157–162”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [159]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 28 · Cited by 155
- Authors
- Percy, M. J., Furlow, P. W., Beer, P. A., Lappin, T. R. J., McMullin, M. F., & Lee, F. S.
- Affiliations
- Belfast City Hospital (GB)
- University of Pennsylvania (US)
- Addenbrooke's Hospital (GB)
- Queen's University Belfast (GB)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-09-15
- Volume
- 110
- Issue
- 6
- Pages
- 2193-2196
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1976349
- OpenAlex
- W2056714071
- Cited by
- 155
- References
- 28
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 4 · 2014: 8 · 2013: 12 · 2012: 5
- FWCI
- 12.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- U.S. Public Health Service (R01 C090261)
- 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 › Hemoglobinopathies and Related Disorders
- Keywords
- erythrocytosis, PHD2, prolyl hydroxylase, erythropoietin regulation, von Hippel-Lindau protein, red cell disorders, hypoxia
- MeSH terms
- Adult, Humans, Male, Mutation, Polycythemia, Procollagen-Proline Dioxygenase, Receptors, Erythropoietin, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia-Inducible Factor-Proline Dioxygenases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
