|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “egl-9 family hypoxia-inducible factor 1.”
EGLN1 is the gene's official symbol. The EGLN1 gene is also known by other names, listed below.
The EGLN1 gene, often known as PHD2, provides instructions for making an enzyme called prolyl hydroxylase domain 2 (PHD2). The PHD2 enzyme interacts with a protein called hypoxia-inducible factor 2-alpha (HIF-2α). This protein is one part (subunit) of a larger HIF protein complex that plays a critical role in the body's ability to adapt to changing oxygen levels. HIF controls several important genes involved in cell division, the formation of new blood vessels, and the production of red blood cells. It is the major regulator of a hormone called erythropoietin, which controls red blood cell production.
The PHD2 enzyme's primary job is to target HIF-2α to be broken down (degraded) so it does not build up when it is not needed. When enough oxygen is available, the PHD2 enzyme is highly active to stimulate the breakdown of HIF-2α. However, when oxygen levels are lower than normal (hypoxia), the PHD2 enzyme becomes less active. As a result, HIF-2α is degraded more slowly, leaving more HIF available to stimulate the formation of new blood vessels and red blood cells. These activities help maximize the amount of oxygen that can be delivered to the body's organs and tissues.
Studies suggest that the EGLN1 gene is involved in the body's adaptation to high altitude. At higher altitudes, such as in mountainous regions, air pressure is lower and less oxygen enters the body through the lungs. Over time, the body compensates for the lower oxygen levels by changing breathing patterns and producing more red blood cells and blood vessels.
Researchers suspect that the EGLN1 gene may also act as a tumor suppressor gene because of its role in regulating cell division and other processes through its interaction with HIF. Tumor suppressors prevent cells from growing and dividing too fast or in an uncontrolled way, which could lead to the development of a tumor.
The EGLN1 gene belongs to a family of genes called ZMYND (zinc fingers, MYND-type).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
At least 10 mutations in the EGLN1 gene have been found to cause familial erythrocytosis, an inherited condition characterized by an increased number of red blood cells and an elevated risk of abnormal blood clots. When familial erythrocytosis results from EGLN1 gene mutations, it is often designated ECYT3.
Some EGLN1 gene mutations change single protein building blocks (amino acids) in the PHD2 enzyme, while others lead to the production of an abnormally short version of the enzyme. Any of these genetic changes disrupt the enzyme's ability to interact with HIF-2α and target it for destruction. Consequently, HIF accumulates in cells even when adequate oxygen is available. The presence of extra HIF leads to the production of red blood cells when no more are needed, resulting in an excess of these cells in the bloodstream.
At least one of the known EGLN1 gene mutations has been associated with both familial erythrocytosis and a tumor called a paraganglioma in the same individual. Paragangliomas are noncancerous (benign) tumors of the nervous system. The mutation, written as His374Arg or H374R, replaces the amino acid histidine with the amino acid arginine at position 374 in the PHD2 enzyme. This genetic change alters the interaction between the PHD2 enzyme and HIF-2α, which leads to the production of excess red blood cells. However, it is unclear how the mutation may be associated with the development of paragangliomas.
Cytogenetic Location: 1q42.1
Molecular Location on chromosome 1: base pairs 231,499,496 to 231,560,789
The EGLN1 gene is located on the long (q) arm of chromosome 1 at position 42.1.
More precisely, the EGLN1 gene is located from base pair 231,499,496 to base pair 231,560,789 on chromosome 1.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about EGLN1 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; adaptation ; amino acid ; benign ; cell ; cell division ; domain ; enzyme ; familial ; gene ; hormone ; mutation ; nervous system ; oxygen ; proteasome ; protein ; red blood cell ; subunit ; tumor ; tumor suppressor gene ; ubiquitin
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.