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.
Health Conditions Related to Genetic Changes
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.More About This Health Condition
Other Names for This Gene
- homogentisate 1,2-dioxygenase (homogentisate oxidase)
- Homogentisic acid oxidase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- 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. Citation on PubMed
- 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. 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, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK1454/ Citation on PubMed
- 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. Citation on PubMed
- 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. 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. Citation on PubMed