ArticleMolecular biology and evolution2023
High-Altitude Andean H194R HIF2A Allele Is a Hypomorphic Allele.
Article in Molecular biology and evolution, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Chronic Cerebral Hypoxia and Cognitive Impairment: A Systematic Review and Meta-Analysis Based on Chronic Mountain Sickness, Anemia, Chronic Obstructive Pulmonary Disease, and Obstructive Sleep Apnea.CNS neuroscience & therapeutics · 2026Pooled it
- Genomic Evidence for Natural Selection Underlying High-Altitude Adaptive Hemoglobin Levels Among Peruvian Andeans.Genome biology and evolution · 2026Article
- Red blood cells serve as a primary glucose sink to improve glucose tolerance at altitude.Cell metabolism · 2026Article
- Genetic adaptations shaping survival, pregnancy, and life at high altitude and sea level.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Advances in Understanding Adaptive Hemoglobin Concentration at High Altitude.American journal of human biology : the official journal of the Human Biology Council · 2025Article
- Convergent Genetic Adaptation in Human Tumors Developed Under Systemic Hypoxia and in Populations Living at High Altitudes.Cancer discovery · 2025Article
- Whole methylomes reveal high-altitude-associated methylation at hypoxia and pigmentation genes in South American Indigenous populations.Environmental epigenetics · 2025Article
- Life destiny of erythrocyte in high altitude erythrocytosis: mechanisms underlying the progression from physiological (moderate) to pathological (excessive) high-altitude erythrocytosis.Frontiers in genetics · 2025Review
- Influence of Hypoxia on the Airway Epithelium.Physiological research · 2024Review
- Higher oxygen content and transport characterize high-altitude ethnic Tibetan women with the highest lifetime reproductive success.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FunctionalScience advances · 2024Article
- Hypoxia Inducible Factor pathway proteins in high-altitude mammals.Trends in biochemical sciences · 2024Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
For over 10,000 years, Andeans have resided at high altitude where the partial pressure of oxygen challenges human survival. Recent studies have provided evidence for positive selection acting in Andeans on the HIF2A (also known as EPAS1) locus, which encodes for a central transcription factor of the hypoxia-inducible factor pathway. However, the precise mechanism by which this allele might lead to altitude-adaptive phenotypes, if any, is unknown. By analyzing whole genome sequencing data from 46 high-coverage Peruvian Andean genomes, we confirm evidence for positive selection acting on HIF2A and a unique pattern of variation surrounding the Andean-specific single nucleotide variant (SNV), rs570553380, which encodes for an H194R amino acid substitution in HIF-2α. Genotyping the Andean-associated SNV rs570553380 in a group of 299 Peruvian Andeans from Cerro de Pasco, Peru (4,338 m), reveals a positive association with increased fraction of exhaled nitric oxide, a marker of nitric oxide biosynthesis. In vitro assays show that the H194R mutation impairs binding of HIF-2α to its heterodimeric partner, aryl hydrocarbon receptor nuclear translocator. A knockin mouse model bearing the H194R mutation in the Hif2a gene displays decreased levels of hypoxia-induced pulmonary Endothelin-1 transcripts and protection against hypoxia-induced pulmonary hypertension. We conclude the Andean H194R HIF2A allele is a hypomorphic (partial loss of function) allele.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.