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Genetics Home Reference: your guide to understanding genetic conditions
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HGD

Reviewed March 2007

What is the official name of the HGD gene?

The official name of this gene is “homogentisate 1,2-dioxygenase.”

HGD is the gene's official symbol. The HGD gene is also known by other names, listed below.

What is the normal function of the HGD gene?

The HGD gene provides instructions for making an enzyme called homogentisate oxidase, which is active chiefly in the liver and kidneys. This enzyme participates in a step-wise process that breaks down two protein building blocks (amino acids), phenylalanine and tyrosine, when they are no longer needed or are present in excess. These two amino acids also play a role in making certain hormones, pigments, and brain chemicals called neurotransmitters.

Homogentisate oxidase is responsible for a specific step in the breakdown of phenylalanine and tyrosine. Previous steps convert the two amino acids into a molecule called homogentisic acid. Homogentisate oxidase adds two oxygen atoms to homogentisic acid, converting it to another molecule called maleylacetoacetate. Other enzymes break down maleylacetoacetate into smaller molecules that are later used for energy or to make other products that can be used by the body.

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

alkaptonuria - caused by mutations in the HGD gene

More than 65 mutations in the HGD gene have been identified in people with alkaptonuria. Most of these mutations change single amino acids used to build the homogentisate oxidase enzyme. For example, a substitution of the amino acid valine for the amino acid methionine at protein position 368 (also written as Met368Val) is the most common HGD mutation in European populations.

Mutations in the HGD gene inactivate homogentisate oxidase by changing its structure. Without a functional version of this enzyme, phenylalanine and tyrosine are not broken down properly and homogentisic acid builds up in the body. Excess homogentisic acid and related compounds are deposited in connective tissues such as cartilage and skin, which causes them to darken. Over time, a buildup of this substance in the joints leads to arthritis. Homogentisic acid is also excreted in urine, making the urine turn dark when exposed to air.

Where is the HGD gene located?

Cytogenetic Location: 3q13.33

Molecular Location on chromosome 3: base pairs 120,628,167 to 120,682,570

The HGD gene is located on the long (q) arm of chromosome 3 at position 13.33.

The HGD gene is located on the long (q) arm of chromosome 3 at position 13.33.

More precisely, the HGD gene is located from base pair 120,628,167 to base pair 120,682,570 on chromosome 3.

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 HGD?

You and your healthcare professional may find the following resources about HGD 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 HGD gene or gene products?

  • AKU
  • HGD_HUMAN
  • HGO
  • homogentisate 1,2-dioxygenase (homogentisate oxidase)
  • Homogentisic acid oxidase
  • homogentisicase

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 HGD?

acids ; amino acid ; arthritis ; breakdown ; cartilage ; enzyme ; gene ; methionine ; molecule ; mutation ; neurotransmitters ; oxidase ; oxygen ; phenylalanine ; protein ; substitution ; tyrosine ; valine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Amaya AA, Brzezinski KT, Farrington N, Moran GR. Kinetic analysis of human homogentisate 1,2-dioxygenase. Arch Biochem Biophys. 2004 Jan 1;421(1):135-42. (http://www.ncbi.nlm.nih.gov/pubmed/14678794?dopt=Abstract)
  • Gene Review: Alkaptonuria (http://www.ncbi.nlm.nih.gov/books/NBK1454/)
  • Goicoechea De Jorge E, Lorda I, Gallardo ME, Pérez B, Peréz De Ferrán C, Mendoza H, Rodríguez De Córdoba S. Alkaptonuria in the Dominican Republic: identification of the founder AKU mutation and further evidence of mutation hot spots in the HGO gene. J Med Genet. 2002 Jul;39(7):E40. (http://www.ncbi.nlm.nih.gov/pubmed/12114497?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3081)
  • Rodríguez JM, Timm DE, Titus GP, Beltrán-Valero De Bernabé D, Criado O, Mueller HA, Rodríguez De Córdoba S, Peñalva MA. Structural and functional analysis of mutations in alkaptonuria. Hum Mol Genet. 2000 Sep 22;9(15):2341-50. (http://www.ncbi.nlm.nih.gov/pubmed/11001939?dopt=Abstract)
  • Srsen S, Müller CR, Fregin A, Srsnova K. Alkaptonuria in Slovakia: thirty-two years of research on phenotype and genotype. Mol Genet Metab. 2002 Apr;75(4):353-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12051967?dopt=Abstract)
  • Zatkova A, Chmelikova A, Polakova H, Ferakova E, Kadasi L. Rapid detection methods for five HGO gene mutations causing alkaptonuria. Clin Genet. 2003 Feb;63(2):145-9. (http://www.ncbi.nlm.nih.gov/pubmed/12630963?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: March 2007
Published: July 28, 2014