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Genetics Home Reference: your guide to understanding genetic conditions
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HPD

Reviewed January 2008

What is the official name of the HPD gene?

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.

What is the normal function of the HPD gene?

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.

How are changes in the HPD gene related to health conditions?

tyrosinemia - caused by mutations in the HPD gene

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.

other disorders - caused by mutations in the HPD gene

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.

Where is the HPD gene located?

Cytogenetic Location: 12q24.31

Molecular Location on chromosome 12: base pairs 121,839,526 to 121,888,610

The HPD gene is located on the long (q) arm of chromosome 12 at position 24.31.

The HPD gene is located on the long (q) arm of chromosome 12 at position 24.31.

More precisely, the HPD gene is located from base pair 121,839,526 to base pair 121,888,610 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about HPD?

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.

What other names do people use for the HPD gene or gene products?

  • 4HPPD
  • 4-HPPD
  • GLOD3
  • HPPD_HUMAN
  • PPD

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding HPD?

acidosis ; acids ; alanine ; amino acid ; cell ; compound ; disability ; 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://ghr.nlm.nih.gov/glossary).

References

  • Aarenstrup L, Falch AM, Jakobsen KK, Neve S, Henriksen L LØ, Tommerup N, Leffers H, Kristiansen K. Expression and post-translational modification of human 4-hydroxy-phenylpyruvate dioxygenase. Cell Biol Int. 2002;26(7):615-25. (http://www.ncbi.nlm.nih.gov/pubmed/12127941?dopt=Abstract)
  • Ellaway CJ, Holme E, Standing S, Preece MA, Green A, Ploechl E, Ugarte M, Trefz FK, Leonard JV. Outcome of tyrosinaemia type III. J Inherit Metab Dis. 2001 Dec;24(8):824-32. (http://www.ncbi.nlm.nih.gov/pubmed/11916315?dopt=Abstract)
  • OMIM: HAWKINSINURIA (http://omim.org/entry/140350)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3242)
  • Rüetschi U, Cerone R, Pérez-Cerda C, Schiaffino MC, Standing S, Ugarte M, Holme E. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III. Hum Genet. 2000 Jun;106(6):654-62. (http://www.ncbi.nlm.nih.gov/pubmed/10942115?dopt=Abstract)
  • Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F. Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. Mol Genet Metab. 2000 Nov;71(3):506-10. (http://www.ncbi.nlm.nih.gov/pubmed/11073718?dopt=Abstract)

 

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.

 
Reviewed: January 2008
Published: December 22, 2014