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URL of this page: https://medlineplus.gov/genetics/gene/hgd/

HGD gene

homogentisate 1,2-dioxygenase

Normal Function

The HGD gene provides instructions for making an enzyme called homogentisate 1,2-dioxygenase, which is active mainly in the liver and kidneys. This enzyme participates in a multi step process that breaks down two protein building blocks (amino acids), phenylalanine and tyrosine. They get broken down when they are no longer needed or when there are too many of them. These two amino acids also play a role in making certain brain chemicals (neurotransmitters), hormones, and pigments.

Homogentisate 1,2-dioxygenase 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 1,2-dioxygenase 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.

Health Conditions Related to Genetic Changes

Alkaptonuria

Hundreds of variants (also called mutations) in the HGD gene have been found to cause alkaptonuria. This condition is characterized by arthritis, kidney stones, areas of dark pigmentation, and dark urine. Most of the HGD gene variants change single amino acids in the homogentisate 1,2-dioxygenase enzyme. These changes severely reduce the function of the homogentisate 1,2-dioxygenase enzyme.

Without a fully functional version of this enzyme, phenylalanine and tyrosine are not broken down properly, and homogentisic acid builds up in the body. Excess homogentisic acid settles in connective tissues and forms a substance called ochronotic pigment, which causes cartilage and skin to darken. Over time, this pigment can build up and harden (calcify), leading to health problems in people with alkaptonuria. Excess homogentisic acid is also excreted in urine, which makes urine turn dark when it is exposed to air.

More About This Health Condition

Other Names for This Gene

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

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

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. doi: 10.1016/j.abb.2003.10.014. Citation on PubMed
  • Bernardini G, Braconi D, Zatkova A, Sireau N, Kujawa MJ, Introne WJ, Spiga O, Geminiani M, Gallagher JA, Ranganath LR, Santucci A. Alkaptonuria. Nat Rev Dis Primers. 2024 Mar 7;10(1):16. doi: 10.1038/s41572-024-00498-x. Citation on PubMed
  • Goicoechea De Jorge E, Lorda I, Gallardo ME, Perez B, Perez De Ferran C, Mendoza H, Rodriguez De Cordoba 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. doi: 10.1136/jmg.39.7.e40. No abstract available. Citation on PubMed or Free article on PubMed Central
  • Introne WJ, Perry M, Chen M. Alkaptonuria. 2003 May 9 [updated 2021 Jun 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1454/ Citation on PubMed
  • Rodriguez JM, Timm DE, Titus GP, Beltran-Valero De Bernabe D, Criado O, Mueller HA, Rodriguez De Cordoba S, Penalva MA. Structural and functional analysis of mutations in alkaptonuria. Hum Mol Genet. 2000 Sep 22;9(15):2341-50. doi: 10.1093/oxfordjournals.hmg.a018927. Citation on PubMed
  • Srsen S, Muller 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. doi: 10.1016/S1096-7192(02)00002-1. Citation on PubMed
  • 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. doi: 10.1034/j.1399-0004.2003.00027.x. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.