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The official name of this gene is “4-hydroxyphenylpyruvate dioxygenase.”
HPD is the gene's official symbol. The HPD gene is also known by other names, listed below.
The HPD gene provides instructions for making an enzyme called 4-hydroxyphenylpyruvate dioxygenase. This enzyme is abundant in the liver, and smaller amounts are found in the kidneys. It is one of a series of enzymes needed to break down the amino acid tyrosine, a protein building block found in many foods. Specifically, 4-hydroxyphenylpyruvate dioxygenase converts a tyrosine byproduct called 4-hydroxyphenylpyruvate to homogentisic acid. In reactions with other enzymes in the series, homogentisic acid is broken down to smaller molecules that are either excreted by the kidneys or used to produce energy.
Researchers have identified several HPD mutations that cause type III tyrosinemia. Some of these mutations change one of the building blocks (amino acids) used to make the 4-hydroxyphenylpyruvate dioxygenase enzyme. Other mutations lead to an unusually small enzyme that is missing many amino acids. As a result of these mutations, the activity of the 4-hydroxyphenylpyruvate dioxygenase enzyme is unusually low or absent. With inadequate enzyme activity, researchers believe that 4-hydroxyphenylpyruvate is converted to a toxic compound instead of homogentisic acid. As this toxic compound builds up, it can impair cell functions, particularly in the nervous system. Impaired nerve cells could lead to the characteristic features of type III tyrosinemia, which include intellectual disability, seizures, and problems with balance and coordination.
One particular HPD mutation can cause a rare condition called hawkinsinuria. In infants, this condition is characterized by a failure to gain weight and grow at the expected rate (failure to thrive) and abnormally high acid levels in the blood (acidosis). The HPD mutation replaces the amino acid alanine with the amino acid threonine at position 33 in the 4-hydroxyphenylpyruvate dioxygenase enzyme. This mutation (written as Ala33Thr or A33T) reduces the activity of the 4-hydroxyphenylpyruvate dioxygenase enzyme. As a result, 4-hydroxyphenylpyruvate is not efficiently converted to homogentisic acid. Instead, some 4-hydroxyphenylpyruvate forms an unusual sulfur-containing amino acid called hawkinsin. It remains unclear how the HPD mutation leads to the features of hawkinsinuria.
Cytogenetic Location: 12q24-qter
Molecular Location on chromosome 12: base pairs 122,277,432 to 122,326,516
The HPD gene is located on the long (q) arm of chromosome 12 between position 24 and the end (terminus) of the arm.
More precisely, the HPD gene is located from base pair 122,277,432 to base pair 122,326,516 on chromosome 12.
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 HPD 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.
acidosis ; acids ; amino acid ; cell ; compound ; enzyme ; failure to thrive ; gene ; mutation ; nervous system ; protein ; threonine ; toxic ; tyrosine
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.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.