ReviewBlood reviews2019
Update on mutations in the HIF: EPO pathway and their role in erythrocytosis.
Review in Blood reviews, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- USP10 regulates HIF2α stability by deubiquitinating HIF2α regardless ofTranslational andrology and urology · 2026Article
- Current research on the HIF-2α-EPO-Hb axis in hypoxic environments: from molecular mechanisms to clinical.Frontiers in medicine · 2026Review
- High-altitude polycythemia: State-of-the-art review.Therapeutic advances in hematology · 2026Review
- Xinnaoxin tablets ameliorate high-altitude polycythemia-associated cardiac injury by regulating the NF-κB, MAPK, and PI3K/AKT signaling pathways.Frontiers in pharmacology · 2026Article
- The Inflammatory Milieu Exacerbates Anemia of Chronic Kidney Disease: From the Gut-Kidney Axis to Bone Marrow Hematopoiesis Inhibition.Kidney & blood pressure research · 2026Review
- Advances in Understanding Adaptive Hemoglobin Concentration at High Altitude.American journal of human biology : the official journal of the Human Biology Council · 2025Article
- Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A.Diabetes & metabolism journal · 2025Article
- Pilot Study on the Profiling and Functional Analysis of mRNA, miRNA, and lncRNA in the Skeletal Muscle of Mongolian Horses, Xilingol Horses, and Grassland-Thoroughbreds.Animals : an open access journal from MDPI · 2025Article
- Two Novel Genetic Variants Involved in the Oxygen Sensing Pathway in JAK2-unmutated Erythrocytosis.Biochemical genetics · 2025Article
- Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025Review
- Angiogenesis of Avascular Necrosis of the Femoral Head: A Classic Treatment Strategy.Biomedicines · 2024Review
- Expression and Variations inAnimals : an open access journal from MDPI · 2024Article
- Hypoxia Inducible Factor pathway proteins in high-altitude mammals.Trends in biochemical sciences · 2024Review
- Relationship between ZHX2 Expression and VHL Gene Alteration in VHL-associated and Sporadic Hemangioblastomas of the Central Nervous System.Journal of kidney cancer and VHL · 2024Article
- High altitude polycythemia and its maladaptive mechanisms: an updated review.Frontiers in medicine · 2024Review
- Potential therapeutic effects of traditional Chinese medicine in acute mountain sickness: pathogenesis, mechanisms and future directions.Frontiers in pharmacology · 2024Review
- The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions.iScience · 2023Article
- Characterization of genetic variants in theHaematologica · 2023Article
- High-Altitude Andean H194R HIF2A Allele Is a Hypomorphic Allele.Molecular biology and evolution · 2023Article
- Hemangioblastomas and Other Vascular Origating Tumors of Brain or Spinal Cord.Advances in experimental medicine and biology · 2023Review
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Authors and funding
2 authors.
Funding
Abstract
Identification of the underlying defects in congenital erythrocytosis has provided mechanistic insights into the regulation of erythropoiesis and oxygen homeostasis. The Hypoxia Inducible Factor (HIF) pathway plays a key role in this regard. In this pathway, an enzyme, Prolyl Hydroxylase Domain protein 2 (PHD2), constitutively prolyl hydroxylates HIF-2α, thereby targeting HIF-2α for degradation by the von Hippel Lindau (VHL) tumor suppressor protein. Under hypoxia, this modification is attenuated, resulting in the stabilization of HIF-2α and transcriptional activation of the erythropoietin (EPO) gene. Circulating EPO then binds to the EPO receptor (EPOR) on red cell progenitors in the bone marrow, leading to expansion of red cell mass. Loss of function mutations in PHD2 and VHL, as well as gain of function mutations in HIF-2α and EPOR, are well established causes of erythrocytosis. Here, we highlight recent developments that show that the study of this condition is still evolving. Specifically, novel mutations have been identified that either change amino acids in the zinc finger domain of PHD2 or alter splicing of the VHL gene. In addition, continued study of HIF-2α mutations has revealed a distinctive genotype-phenotype correlation. Finally, novel mutations have recently been identified in the EPO gene itself. Thus, the cascade of genes that at a molecular level leads to EPO action, namely PHD2 - > HIF2A - > VHL - > EPO - > EPOR, are all mutational targets in congenital erythrocytosis.
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