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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®


Reviewed August 2015

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 second in a series of five enzymes that work 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. Continuing the process, homogentisic acid is further broken down and ultimately smaller molecules are produced that are either excreted by the kidneys or used to produce energy or make other substances in the body.

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

tyrosinemia - caused by mutations in the HPD gene

Researchers have identified at least six HPD gene mutations that cause tyrosinemia type III. This condition is characterized by neurological problems such as intellectual disability, seizures, and periodic loss of balance and coordination (intermittent ataxia). Some of the mutations that cause this condition change single amino acids in the 4-hydroxyphenylpyruvate dioxygenase enzyme. Other mutations lead to the production of an unusually small enzyme. As a result of these mutations, the activity of the 4-hydroxyphenylpyruvate dioxygenase enzyme is unusually low or absent. As a result, the enzyme cannot perform its role in the breakdown of tyrosine, so 4-hydroxyphenylpyruvate is converted to toxic compounds instead of homogentisic acid. As these toxic compounds builds up in cells, they can impair function and eventually cause cell death. Cells in the nervous system are particularly sensitive to this toxic accumulation. Nerve cell damage and death likely lead to the characteristic features of tyrosinemia type III.

other disorders - caused by mutations in the HPD gene

At least two HPD gene mutations have been found to 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 gene mutations that cause hawkinsinuria result in decreased enzyme activity so that 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 production of hawkinsin leads to the features of hawkinsinuria.

Where is the HPD gene located?

Cytogenetic Location: 12q24.31

Molecular Location on chromosome 12: base pairs 121,839,527 to 121,888,611

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 121,839,527 to base pair 121,888,611 on chromosome 12.

See How do geneticists indicate the location of a gene? ( 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
  • P-hydroxyphenylpyruvate hydroxylase
  • P-hydroxyphenylpyruvate oxidase
  • PPD

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding HPD?

acidosis ; acids ; amino acid ; ataxia ; breakdown ; cell ; disability ; enzyme ; failure to thrive ; gene ; nerve cell ; nervous system ; neurological ; oxidase ; protein ; toxic ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • 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. (
  • Brownlee JM, Heinz B, Bates J, Moran GR. Product analysis and inhibition studies of a causative Asn to Ser variant of 4-hydroxyphenylpyruvate dioxygenase suggest a simple route to the treatment of Hawkinsinuria. Biochemistry. 2010 Aug 24;49(33):7218-26. doi: 10.1021/bi1008112. (
  • 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. (
  • Heylen E, Scherer G, Vincent MF, Marie S, Fischer J, Nassogne MC. Tyrosinemia Type III detected via neonatal screening: management and outcome. Mol Genet Metab. 2012 Nov;107(3):605-7. doi: 10.1016/j.ymgme.2012.09.002. Epub 2012 Sep 7. (
  • NCBI Gene (
  • 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. (
  • 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. (


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? ( in the Handbook.

Reviewed: August 2015
Published: November 23, 2015