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The official name of this gene is “gephyrin.”
GPHN is the gene's official symbol. The GPHN gene is also known by other names, listed below.
The GPHN gene provides instructions for making a protein called gephyrin, which has two major functions in the body: the protein aids in the formation (biosynthesis) of a molecule called molybdenum cofactor, and it also plays a role in communication between nerve cells (neurons).
Gephyrin performs the final two steps in molybdenum cofactor biosynthesis. Molybdenum cofactor, which contains the element molybdenum, is essential to the function of several enzymes called sulfite oxidase, aldehyde oxidase, xanthine dehydrogenase, and mitochondrial amidoxime reducing component (mARC). These enzymes help break down (metabolize) different substances in the body, some of which are toxic if not metabolized.
Gephyrin also plays an important role in neurons. Communication between neurons depends on chemicals called neurotransmitters. To relay signals, a neuron releases neurotransmitters, which attach to receptor proteins on neighboring neurons. Gephyrin anchors certain receptor proteins to the correct location in neurons so that the receptors can receive the signals relayed by neurotransmitters.
GPHN gene mutations cause a disorder called molybdenum cofactor deficiency. This disorder is characterized by seizures that begin early in life and brain dysfunction that worsens over time (encephalopathy); the condition is usually fatal by early childhood. At least two mutations in the GPHN gene have been found to cause a form of the disorder designated type C or complementation group C. This is the rarest form of the condition, affecting only a small number of individuals.
The GPHN gene mutations involved in molybdenum cofactor deficiency likely reduce or eliminate the function of gephyrin. The known mutations impair gephyrin's ability to perform one or both of the final two steps of molybdenum cofactor biosynthesis. Without the cofactor, the metabolic enzymes that rely on it cannot function.
The resulting loss of enzyme activity leads to buildup of certain chemicals, including sulfite, S-sulfocysteine, xanthine, and hypoxanthine, and low levels of another chemical called uric acid. (Testing for these chemicals can help in the diagnosis of this condition.) Sulfite, which is normally broken down by sulfite oxidase, is toxic, especially to the brain. Researchers suggest that damage caused by the abnormally high levels of sulfite (and possibly other chemicals) leads to encephalopathy, seizures, and the other features of molybdenum cofactor deficiency.
Cytogenetic Location: 14q23.3
Molecular Location on chromosome 14: base pairs 66,507,406 to 67,181,807
The GPHN gene is located on the long (q) arm of chromosome 14 at position 23.3.
More precisely, the GPHN gene is located from base pair 66,507,406 to base pair 67,181,807 on chromosome 14.
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 GPHN 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.
aldehyde ; cofactor ; deficiency ; dehydrogenase ; diagnosis ; encephalopathy ; enzyme ; gene ; hereditary ; molecule ; neuron ; neurotransmitters ; oxidase ; protein ; receptor ; toxic ; uric acid
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.